SNPMiner Trials by Shray Alag


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Report for Mutation D816V

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 17 clinical trials

Clinical Trials


1 Efficacy of Tyrosine Kinase Inhibition in Reducing Eosinophilia in Patients With Myeloid and/or Steroid-Refractory Hypereosinophilic Syndrome

The purpose of this study is to evaluate the safety and efficacy of the tyrosine kinase inhibitor, imatinib mesylate (Gleevec ) in reducing peripheral blood eosinophilia in patients with the myeloid form of hypereosinophilic syndrome (HES). Patients with the hypereosinophilic syndrome who meet a set of criteria designed to select patients with the myeloid form of the disease, as well as patients without myeloid disease who are refractory to standard therapy for HES, will be admitted on this protocol. A thorough clinical evaluation will be performed with emphasis on potential sequelae of eosinophil-mediated tissue damage. A baseline bone marrow will be obtained to exclude leukemia or lymphoma and to assess the degree and nature of eosinophilopoiesis. Bone marrow, blood cells and/or serum will also be collected to test for the presence of a recently described mutation that is associated with imatinib-responsiveness in HES, and to provide reagents (such as DNA, RNA, and specific antibodies) and for use in the laboratory to address issues related to the mechanism of action of imatinib mesylate in HES. Imatinib mesylate will be initiated at a dose of 400 mg daily, the FDA-approved dose for the treatment of chronic myelogenous leukemia. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100mg daily and then discontinued. In order to minimize bone marrow suppression, other myelosuppressive agents will be tapered and discontinued during the first week of therapy with imatinib mesylate. Complete blood counts will be performed weekly for the first month and biweekly thereafter. Clinical assessments will be performed every three months to assess progression of end organ damage. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100 mg daily and then discontinued. In the event of clinical, hematologic or molecular relapse during the taper, the imatinib dose will be increased to a maximum of 600 mg daily to achieve a second remission. Laboratory monitoring will be performed as above except for molecular monitoring which will be monitored monthly if drug is discontinued or molecular relapse occurs. Once a stable dosing regimen is achieved for greater than or equal to 6 months in subjects who have undergone dose descalation or greater than or equal to 2 years in subjects receiving 300-400 mg of imatinib daily who did not qualify for dose de-escalation, the frequency of NIH visits and end organ assessments will be decreased to 6 months, with molecular monitoring every 3 months and monthly routine laboratory assessments.

NCT00044304 Hypereosinophilic Syndrome Drug: Imatinib Drug: Ruxolitinib
MeSH: Hypereosinophilic Syndrome Syndrome

EXCLUSION CRITERIA: 1. Pregnancy or nursing women 2. HIV positivity or other known immunodeficiency 3. D816V KIT-positive systemic mastocytosis 4. Absolute neutrophil count less than 1000/mm(3) or platelet count less than 10,000/mm(3) or less than 50,000/m(3) with clinical evidence of bleeding. --- D816V ---

Primary Outcomes

Description: The percentage of subjects who reach and eosinophil count in the normal range

Measure: peripheral blood absolute eosinophil count.

Time: one month (for imatinib) and 3 months (for ruxolitinib).

Secondary Outcomes

Description: The % of subjects who reach an eosinophil count in the normal range

Measure: peripheral blood eosinophil count

Time: 3,6,9 and 12 months

Description: The % of subjects who reach an eosinophil count below 1500/mm3

Measure: peripheral blood eosinophil count

Time: 1, 3, 6, 9, and 12 months

Description: The % of subjects who achieve molecular remission on therapy

Measure: abnormal tyrosine kinase (i.e., FIP1L1-PDGFRA, JAK2 V617F)

Time: every 3 months for 5 years

Description: The duration of remission following cessation of therapy

Measure: clinical, hematologic and molecular remission

Time: every 3 months for 5 years

2 Imatinib Mesylate in Patients With Various Types of Malignancies Involving Activated Tyrosine Kinase Enzymes

This trial is for various types of malignancies which may depend on certain enzymes (tyrosine kinases) for growth. The objective of this study is to assess to what extent imatinib mesylate blocks these enzymes and to assess the effect on the malignancy.

NCT00171912 Hypereosinophilic Syndrome Systemic Mastocytosis Chronic Myelomonocytic Leukemia Dermatofibrosarcoma Drug: imatinib mesylate
MeSH: Leukemia Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Mastocytosis Mastocytosis, Systemic Dermatofibrosarcoma Hypereosinophilic Syndrome Neoplasms
HPO: Chronic myelomonocytic leukemia Juvenile myelomonocytic leukemia Leukemia Mastocytosis Neoplasm

Exclusion Criteria: 1. Certain leukaemias (abl-mutated), some gastrointestinal stromal tumours (c-KIT-positive) or certain systemic mastocytosis (if c- KIT D816V mutation). --- D816V ---

Not included: Patients with chronic myeloid leukemia, some other types of leukemias (abl-mutated) some types of gastrointestinal stromal tumours (c-KIT-positive), some systemic mastocytosis (if c-KIT D816V mutation), brain, prostate, breast or lung cancers. --- D816V ---

Primary Outcomes

Measure: To assess the efficacy and the safety of imatinib mesylate therapy

Time: 2 years

Secondary Outcomes

Measure: To evaluate the effects of imatinib on quality of life and healthcare resource use

Time: 2 years

3 Investigation of Cellular and Molecular Pathologic Mechanisms in Mast Cell Disorders.

Mastocytosis is a disorder characterized by presence of excessive numbers of mast cells in skin, bone marrow and internal organs. It can affect both children and adults, males and females and individuals from all ethnic backgrounds, although precise demographic information about the affected populations is not available as it is a rare disorder. Mastocytosis in children is generally limited to the skin and follows a self limited course, while it is a disorder of the hematopoietic stem cell associated with somatic mutations of the c-kit gene in most patients with adult-onset of disease. There is no known curative therapy for most patients with systemic mastocytosis. Recent research studies identified several subtypes of disease with distinct clinical and pathologic features, however, a precise understanding of the incidence as well as molecular pathology of different disease subtypes is lacking. This study aims to examine molecular and cellular pathological aspects of disease in patients with mastocytosis and correlate findings with clinical presentation and prognosis. Patients will undergo a routine history and physical examination, and diagnostic tests will be ordered as dictated by each patient's clinical presentation. Blood and bone marrow will be obtained for diagnostic and research purposes. Genetic analysis of the c-kit gene regulating mast cell growth and differentiation will be performed. It is hoped that findings obtained from this study will help to design novel therapies for mastocytosis and other disorders in which mast cells play a critical role.

NCT00336076 Mastocytosis Other: Collection of blood and bone marrow
MeSH: Mastocytosis
HPO: Mastocytosis

Proportion of KIT D816V mutation in blood, bone marrow and sorted mast cells. --- D816V ---

KIT D816V mutation was assessed in patient samples containing various proportions of neoplastic mast cells.. Inclusion Criteria: - Confirmed or suspected diagnosis of mastocytosis. --- D816V ---

Primary Outcomes

Description: Patients were categorized into one of the clonal and non-clonal mast cell disorder categories after availability of diagnostic data

Measure: Proportion of the patients with clonal and non-clonal mast cell disorders

Time: 1 week

Secondary Outcomes

Description: KIT D816V mutation was assessed in patient samples containing various proportions of neoplastic mast cells.

Measure: Proportion of KIT D816V mutation in blood, bone marrow and sorted mast cells

Time: 1 week

4 Phase II Study of Thalidomide in Mastocytosis

RATIONALE: Thalidomide may stop the growth of systemic mastocytosis by blocking blood flow to the disease. PURPOSE: This phase II trial is studying how well thalidomide works in treating patients with relapsed or progressive systemic mastocytosis.

NCT00769587 Non Neoplastic Condition Precancerous Condition Drug: thalidomide
MeSH: Mastocytosis Precancerous Conditions Mastocytosis, Systemic Disease
HPO: Mastocytosis

DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial Non Neoplastic Condition Precancerous Condition Mastocytosis Precancerous Conditions Mastocytosis, Systemic Disease OBJECTIVES: Primary - Determine the objective response rate at 6 months in patients with systemic mastocytosis treated with thalidomide. --- D816V ---

DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial Non Neoplastic Condition Precancerous Condition Mastocytosis Precancerous Conditions Mastocytosis, Systemic Disease OBJECTIVES: Primary - Determine the objective response rate at 6 months in patients with systemic mastocytosis treated with thalidomide. --- D816V --- --- D816V ---

Primary Outcomes

Measure: Objective reduction of the infiltration rate at 6 months

Time: 6 months

5 Randomized, Placebo-controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib at 6 mg/kg/Day to Placebo in Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

The objective of this study is to compare the safety and efficacy of masitinib (AB1010) to placebo in patients with mastocytosis with handicap.

NCT00814073 Indolent Systemic Mastocytosis Drug: Masitinib Drug: Placebo Other: Best Supportive Care
MeSH: Mastocytosis Mastocytosis, Systemic
HPO: Mastocytosis

The objective of this phase 3 study was therefore to evaluate masitinib efficacy and safety in severe systemic mastocytosis patients, with or without D816V mutation of c-Kit. --- D816V ---

Primary Outcomes

Description: The prospectively declared primary endpoint (4R75%) was cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response was defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).

Measure: Cumulative response (4R75%)

Time: 24 weeks

Secondary Outcomes

Description: Cumulative response in at least one of three severe baseline symptoms (pruritus, flushes, or depression)

Measure: Cumulative response (3R75%)

Time: 24 weeks

Description: Cumulative response in at least one of three severe baseline symptoms (pruritus or flushes)

Measure: Cumulative response (2R75%)

Time: 24 weeks

6 Phase IIa, Open-label, Randomized Study of Oral AB1010 in Patients With Systemic Indolent Mastocytosis With Handicap and Not Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V)

This is a 12 weeks study aimed at assessing the safety and efficacy of 2 doses of AB1010 in patients suffering from indolent systemic mastocytosis with handicap.

NCT00831974 Mastocytosis Drug: masitinib (AB1010) Drug: masitinib (AB1010)
MeSH: Mastocytosis
HPO: Mastocytosis

Phase IIa, Open-label, Randomized Study of Oral AB1010 in Patients With Systemic Indolent Mastocytosis With Handicap and Not Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val ---

Phase IIa, Open-label, Randomized Study of Oral AB1010 in Patients With Systemic Indolent Mastocytosis With Handicap and Not Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val --- --- D816V ---

3. The absence of an activating point mutation in the phosphotransferase domain of c-Kit such as D816V c-Kit mutation in at least one of the two infiltrated organs: bone marrow and/or skin and/or other tissue. --- D816V ---

Primary Outcomes

Measure: Response on: Pruritus score, Number of flush per day, Pollakyuria (on a daily basis), Number of stools per day, QLQ-C30 score, Hamilton Rating Scale for depression

Time: 12 weeks

Secondary Outcomes

Measure: AFIRMM score, reduction of organ infiltration,level of tryptase, reduction on bio markers (TNFα, eosinophils, histamine levels), pharmacokinetic profile of AB1010

Time: 12 weeks

7 A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V)

The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V).

NCT01266369 Mastocytosis Drug: masitinib
MeSH: Mastocytosis
HPO: Mastocytosis

A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val ---

A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val --- --- D816V ---

Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). --- D816V ---

Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). --- D816V --- --- Asp-816-Val ---

Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). --- D816V --- --- Asp-816-Val --- --- D816V ---

Pruritus score at week 12 Number of flushes per week at week 12 Hamilton score at week 12 Fatigue Impact scale at week 12. Inclusion Criteria: 1. Patients with one of the following documented mastocytosis: - Smouldering systemic mastocytosis - Indolent systemic mastocytosis with organomegaly - Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow) - Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance - Cutaneous Mastocytosis (CM) 2. Skin biopsy-documented mastocytosis and evaluable disease based upon: - Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy - Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma) 3. Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin) 4. Refractory to at least one of the symptomatic treatments such as: - Anti H1 - Anti H2 - Proton pump inhibitor - Osteoclast inhibitor - Cromoglycate Sodium - Antileukotriene - Other therapies used for the symptomatic care 5. Handicap defined as at least one of the following handicaps: - pruritus score ≥ 6 - number of flushes per week ≥ 7 - number of stools per day ≥ 4 , - number of mictions per day ≥ 8 , - QLQ-C30 score ≥ 60, - Hamilton score ≥ 10 Exclusion Criteria: 1. Patients with one of the following mastocytosis: - Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) - Mast cell leukemia (MCL) - Aggressive systemic mastocytosis (ASM) 2. Patient with a major surgery within 2 weeks prior to study entry 3. --- D816V ---

- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection Inclusion Criteria: 1. Patients with one of the following documented mastocytosis: - Smouldering systemic mastocytosis - Indolent systemic mastocytosis with organomegaly - Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow) - Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance - Cutaneous Mastocytosis (CM) 2. Skin biopsy-documented mastocytosis and evaluable disease based upon: - Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy - Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma) 3. Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin) 4. Refractory to at least one of the symptomatic treatments such as: - Anti H1 - Anti H2 - Proton pump inhibitor - Osteoclast inhibitor - Cromoglycate Sodium - Antileukotriene - Other therapies used for the symptomatic care 5. Handicap defined as at least one of the following handicaps: - pruritus score ≥ 6 - number of flushes per week ≥ 7 - number of stools per day ≥ 4 , - number of mictions per day ≥ 8 , - QLQ-C30 score ≥ 60, - Hamilton score ≥ 10 Exclusion Criteria: 1. Patients with one of the following mastocytosis: - Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) - Mast cell leukemia (MCL) - Aggressive systemic mastocytosis (ASM) 2. Patient with a major surgery within 2 weeks prior to study entry 3. --- D816V ---

Primary Outcomes

Description: Pruritus score at week 12 Number of flushes per week at week 12 Hamilton score at week 12 Fatigue Impact scale at week 12

Measure: efficacy on handicaps

Time: week 12

8 Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations

The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Imatinib Mesylate therapy in patients with systemic mastocytosis lacking KIT mutations.

NCT01297777 Systemic Mastocytosis Drug: Imatinib Mesylate
MeSH: Mastocytosis Mastocytosis, Systemic
HPO: Mastocytosis

Systemic Mastocytosis Mastocytosis Mastocytosis, Systemic In vitro studies have proven that imatinib inhibits wild type Kit (wtKit) and suppresses proliferation of the HMC-1V560G cell line, while it is ineffective on inhibiting the growth of HMC-1V560G, D816V cells. --- D816V ---

In contrast, several experiments have provided compelling evidence regarding the resistance against the growth-inhibitory effects of imatinib on cells carrying the D816V KIT mutation. --- D816V ---

Primary Outcomes

Description: The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients with B or C findings

Measure: To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration.

Time: 6 months

Description: The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients without B or C findings, and from those with B or C findings who show response at the intermediate check-point (after 6 months of therapy)

Measure: To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration.

Time: 12 months

Secondary Outcomes

Description: Skin lesions are evaluated before and after therapy by macroscopic examination and skin biopsy.

Measure: To evaluate the effect of Imatinib Mesylate on mastocytosis skin lesions.

Time: 12 months

Description: Clinical symptoms such as pruritus, flushing, gastrointestinal symptoms and anaphylaxis are assessed before and after therapy using a clinical questionnaire that includes the type, frequency and severity of each symptom.

Measure: To evaluate the effect of Imatinib Mesylate on mastocytosis mast-cell related symptoms.

Time: 12 months

Description: Organomegalies and adenomegalies are assessed before and after therapy by abdominal ultrasound.

Measure: To evaluate the effect of Imatinib Mesylate on mastocytosis-related megalies.

Time: 12 months

Description: Bone alterations are assessed before and after therapy by X-ray survey.

Measure: To evaluate the effect of Imatinib Mesylate on mastocytosis-related bone alterations.

Time: 12 months

Description: Genetic abnormalities are assessed before and after therapy by sequencyng analysis of the c-kit gene and the HUMARA assay.

Measure: To investigate changes after Imatinib Mesilate therapy in mast cell clonality.

Time: 12 months

Description: Serum tryptase is measured before and after therapy.

Measure: To determine the effect of Imatinib Mesylate therapy on serum tryptase levels.

Time: 12 months

Description: The psychological impact of the disease and the quality of life of patients are evaluated before and after therapy by the Dermatology Life Quality Index.

Measure: To determine the effect of Imatinib Mesylate therapy in the psychological impact of the disease and the quality of life.

Time: 12 months

9 Detection of Clonal Mast Cell Disorders Among Patients With Exercise-induced Anaphylaxis

Anaphylaxis is a serious allergic reaction that develops rapidly and can cause death. Some patients experience anaphylaxis is association with exercise, a disorder called exercise-induced anaphylaxis. A subset of patients with unexplained anaphylaxis, especially those with hypotension during the anaphylactic episodes, have been shown to have abnormal, clonal populations of a certain cell type, mast cells, in the bone marrow. This has been described in at least one patient with exercise-induced anaphylaxis. The investigators would like review the findings in a group of patients with exercise-induced anaphylaxis who have undergone evaluation for the presence of abnormal, clonal mast cells.

NCT01326741 Anaphylaxis
MeSH: Mastocytosis Anaphylaxis Shock
HPO: Anaphylactic shock Mastocytosis

Presence of clonal mast cells in bone marrow as assessed by D816V c-kit mutation or CD25 will be recorded for each participant.. Number of participants with presence of clonal abnormalities in the bone marrow specimen. --- D816V ---

Presence of clonal mast cells in bone marrow as assessed by D816V c-kit mutation or CD25 will be recorded for each participant. --- D816V ---

Primary Outcomes

Description: Presence of clonal mast cells in bone marrow as assessed by D816V c-kit mutation or CD25 will be recorded for each participant.

Measure: Number of participants with presence of clonal abnormalities in the bone marrow specimen

Time: Baseline

Description: Presence of clonal mast cells in bone marrow as assessed by D816V c-kit mutation or CD25 will be recorded for each participant. The data will be reported as the number of participant with exercise induced anaphylaxis carrying these clonal mast cells in this observational study. Presence of mast cells will be correlated with clinical parameters such as symptoms experienced during anapylaxis.

Measure: Number of participants with presence of clonal abnormalities in the bone marrow specimen

Time: Baseline

10 Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.

The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations.

NCT01602939 Systemic Mastocytosis Drug: Cladribine and pegylated interpheron alpha-2a
MeSH: Mastocytosis Mastocytosis, Systemic
HPO: Mastocytosis

Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.. Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations. --- D816V ---

Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.. Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations. --- D816V --- --- D816V ---

- Diagnosis of advanced systemic mastocytosis (aggressive systemic mastocytosis or proggressing systemic mastocytosis) with D816V or other exon 17 KIT mutations. --- D816V ---

Primary Outcomes

Description: Evaluation of bone marrow response will be assessed by immunohistochemestry, citology, flow cytometry and molecular analyses of bone marrow samples.

Measure: To evaluate the effect of therapy on bone marrow mast cell infiltration.

Time: 6 months

Secondary Outcomes

Description: Serum tryptase and any other mastocytosis-related altered biochemical parameter at diagnosis will be measured monthly until the end of therapy.

Measure: To determine the effect of therapy on serum tryptase levels and other altered peripheral blood parameters due to mastocytosis.

Time: 6 months

Description: Specific questionnaires regarding mast cell-mediator release symptoms will be filled monthly by each patient until the end of therapy.

Measure: To evaluate the effect of therapy on mast cell-mediator release symptoms: pruritus, flushing, gastrointestinal symptoms or anaphylaxis).

Time: 6 months

Description: Potentially drugs-related adverse events will be recorded in each case following accepted criteria (NIH CTCAE).

Measure: To determine de safety of combined therapy with low doses of cladribine plus pegylated interpheron alpha-2a.

Time: 6 months

Description: Evaluation of cutaneous response will be assessed by macroscopic inspection including photographs and by skin immunohistochemestry.

Measure: To evaluate the effect of therapy on mastocytosis skin lesions.

Time: 6 moths

Description: Evaluation of organomegalies response will be assessed by abdominal ultrasound and/or computerized tomography.

Measure: To evaluate the effect of therapy on mastocytosis-related organomegalies.

Time: 6 months

Description: Evaluation of bone response will be assessed by X-ray survey and/or computerized tomography.

Measure: To evaluate the effect of therapy on mastocytosis-related bone alterations.

Time: 6 months

11 Phase II Single Arm Open Pilot Study to Demonstrate the Efficacy of Midostaurin in Symptom Improvement and Decrease of Mast Cell Burden in Patients With Indolent or Smoldering Systemic Mastocytosis.

Rationale: Patients with indolent or smoldering systemic mastocytosis can have severe disabling symptoms. Almost all patients have fatigue, a compromised quality of life, hampering normal functioning. Because this form of mastocytosis is not considered life-threatening, mast cell eradication has never been applied and patients receive only symptomatic therapy with histamine blockers. Midostaurin, a c-KIT inhibitor has shown activity regarding symptom control and decrease of malignant mast cells in patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia

NCT01920204 Indolent Systemic Mastocytosis Drug: Midostaurin,
MeSH: Mastocytosis Mastocytosis, Systemic
HPO: Mastocytosis

Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.. Inclusion Criteria: - Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic Mastocytosis (SSM) according to the WHO criteria - Presence of the D816V c-KIT mutation - Serum tryptase > 20 mg/l - Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking drugs. --- D816V ---

- Any known other present malignancy, non-melanoma skin cancers excluded - History of malignancy within the last 5 years, non-melanoma skin cancers excluded - Any serious comorbidity interfering with therapy compliance and follow-up compliance - Pregnancy - Patients not willing or who are not able to comply with contraceptive measures Inclusion Criteria: - Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic Mastocytosis (SSM) according to the WHO criteria - Presence of the D816V c-KIT mutation - Serum tryptase > 20 mg/l - Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking drugs. --- D816V ---

Primary Outcomes

Description: Percent change in the total score ("Sumscore") of all symptoms assessed by the Mastocytosis Symptom Assessment Form (MSAF) after 12 weeks.

Measure: Symptom Scoring

Time: 12 weeks

Secondary Outcomes

Description: persistence of improvement symptom score at 6 months.

Measure: Persistence of improvements

Time: 6 months

Description: Percent change in the mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase levels) after 6 months.

Measure: Mast cell burden

Time: 6 months

Description: Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.

Measure: Adverse events

Time: 6 months

12 Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)

This phase II trial studies how well ponatinib hydrochloride works in treating patients with cancer that has spread to other parts of the body (metastatic), has failed previous treatment (refractory), and has one of several alterations, or mutations, in its deoxyribonucleic acid (DNA) sequence. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether a patient's genetic alterations may affect how well ponatinib hydrochloride works.

NCT02272998 Malignant Neoplasm Drug: ponatinib hydrochloride Other: laboratory biomarker analysis
MeSH: Neoplasms
HPO: Neoplasm

- Patients with known ponatinib-resistant gene alterations - PDGFRA D842V mutation - cKIT D816V mutation - FLT3 D835V/Y/H/F or Y842C mutations - FGFR3 K652E mutation - Major surgery (e.g. --- D842V --- --- D816V ---

Primary Outcomes

Description: The proportion of responses for the purposes of the decision rule will be calculated out of all eligible patients who receive any treatment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.

Measure: Overall response, defined as the number of patients who achieve any response according to disease type in the first 6 courses of treatment

Time: Up to 6 months

Secondary Outcomes

Description: Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the cohorts as well as across cohorts. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.

Measure: Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Time: Up to 30 days after last dose of study drug

Description: Collected and summarized by descriptive statistics. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.

Measure: Tolerability of the regimen, assessed by the number of patients who required dose modifications and/or dose delays

Time: Up to 30 days after last dose of study drug

Description: Kaplan-Meier curves will be used to estimate the survival distribution.

Measure: Overall survival

Time: The time from treatment initiation to death, assessed up to 52 weeks

Description: Kaplan-Meier curves will be used to estimate the survival distribution.

Measure: Progression free survival

Time: The time from treatment initiation to progression or death, assessed up to 52 weeks

Description: Calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for CBR will be calculated.

Measure: Clinical benefit rate (CBR)

Time: 6 months

Other Outcomes

Description: Correlative gene and protein markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. response vs. no response). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement (e.g. response vs. no response). Overall, hypothesis testing will largely be avoided given the sample size limitations.

Measure: Correlative gene and protein markers

Time: Up to 3 years (time of progression)

13 A Phase 1 Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies

This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

NCT02561988 Aggressive Systemic Mastocytosis Systemic Mastocytosis-associated Hematologic Non-mast Cell Disease Mast Cell Leukemia Relapsed or Refractory Myeloid Malignancies Drug: Avapritinib
MeSH: Mastocytosis Mastocytosis, Systemic Leukemia, Mast-Cell Neoplasms
HPO: Mastocytosis Neoplasm

Changes in levels of serum tryptase and levels of V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) D816V allele burden in blood. --- D816V ---

Primary Outcomes

Measure: Maximum tolerated dose (MTD) of avapritinib (also known as BLU-285)

Time: During cycle 1 (28 days) of treatment

Measure: Number of patients with adverse and serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings

Time: Approximately 24 months

Measure: Recommended Phase 2 dose (RP2D) of avapritinib

Time: Approximately 24 months

Secondary Outcomes

Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1

Measure: Maximum plasma concentration of avapritinib

Time: Every cycle (28 days) up to cycle 4

Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1

Measure: Time to maximum plasma concentration of avapritinib

Time: Every cycle (28 days) up to cycle 4

Description: Including complete remission (CR), CR with partial recovery of peripheral blood (CRh), partial remission (PR) and clinical improvement (CI) using modified International Working Group Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European competence network on mastocytosis (ECNM) criteria; and duration of response (DOR)

Measure: Overall Response Rate

Time: 8, 24, 40, 68 and every 24 weeks until patient terminates from the study (approximately 24 months)

Measure: Changes in levels of serum tryptase and levels of V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) D816V allele burden in blood

Time: Cycle (C)1Day (D)1, C1D15, C2D1, C3D1, C5D1, C7D1, C11D1, C18D1 every 6 cycles thereafter and at disease progression. (approximately 24 months)

Description: Defined as change from Baseline

Measure: Changes in patient reported symptoms and quality of life using the Patient Global Impression of Symptom Severity (PGIS) scale

Time: Part 2 only - Day 1 of Cycles 1-12

Description: Defined as change from Baseline

Measure: Changes in patient reported quality of life using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C-30)

Time: Part 2 only - Day 1 of Cycles 1-12

Description: Defined as change from Baseline

Measure: Changes in patient reported outcomes using the advanced SM symptom assessment form (AdvSM-SAF)

Time: Part 2 only - daily from Day -7 through Cycle 12

Description: mL

Measure: Change in liver volume by imaging

Time: Day 1 of Cycles 5-18, and every 6 cycles thereafter (each cycle is 28 days)

Description: mL

Measure: Change in spleen volume by imaging

Time: Day 1 of Cycles 5-18, and every 6 cycles thereafter (each cycle is 28 days)

14 A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Malignancies

This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase and an expansion phase.

NCT02571036 Gastrointestinal Stromal Tumors Advanced Systemic Mastocytosis Advanced Cancers Drug: DCC-2618 Drug: DCC-2618
MeSH: Gastrointestinal Stromal Tumors Mastocytosis Mastocytosis, Systemic
HPO: Gastrointestinal stroma tumor Mastocytosis

Patients with de novo imatinib resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are eligible without prior imatinib therapy. --- D816V ---

Primary Outcomes

Description: Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs.

Measure: Safety/tolerability of oral DCC-2618: incidence of adverse events

Time: Approximately 24 months

Measure: Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose

Time: 18 months

Description: Objective response rate (ORR); Disease control rate (DCR)

Measure: Expansion Phase: Assess Antitumor Activity of DCC-2618 in all diseases

Time: Approximately 24 months

Secondary Outcomes

Measure: Determine the PK profile of oral DCC-2618

Time: Predose and up to 24 hours postdose (Cycle = 28 Days)

Description: Objective response rate (ORR); Disease control rate (DCR)

Measure: Escalation Phase: Assess Antitumor Activity of DCC-2618 in patients with advanced malignancies

Time: Approximately 24 months

15 An Open-label, Single Arm, Phase 2 Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis

This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)

NCT03580655 Advanced Systemic Mastocytosis Aggressive Systemic Mastocytosis Systemic Mastocytosis With an Associated Hematologic Neoplasm Mast Cell Leukemia Drug: Avapritinib
MeSH: Mastocytosis Mastocytosis, Systemic Hematologic Neoplasms Leukemia, Mast-Cell
HPO: Hematological neoplasm Leukemia Mastocytosis

Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) mutation burden. --- D816V ---

Primary Outcomes

Measure: Objective response rate (ORR) based on modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) response criteria

Time: 10 Months

Secondary Outcomes

Description: 0 - 80 points (higher value represents worse symptom outcomes)

Measure: Mean Change from Baseline in Advanced Systemic Mastocytosis-Symptom Assessment Form (AdvSM-SAF) Total Symptom Score

Time: 10 Months

Description: Months

Measure: Time-to-response (TTR)

Time: 10 Months

Description: Months

Measure: Duration of Response (DOR)

Time: 10 Months

Description: Months

Measure: Progression-free Survival (PFS)

Time: 10 Months

Description: Months

Measure: Overall Survival (OS)

Time: 10 Months

Description: percentage

Measure: Changes in bone marrow mast cells

Time: 10 Months

Description: ng/mL

Measure: Change in serum tryptase

Time: 10 Months

Description: percentage

Measure: Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) mutation burden

Time: 10 Months

Description: mL

Measure: Change in liver volume by imaging

Time: 10 Months

Description: mL

Measure: Change in spleen volume by imaging

Time: 10 Months

Measure: Clinical benefit based on modified IWG-MRT-ECNM consensus criteria

Time: 10 Months

Description: 0 - 10 points (higher value represents worse symptom outcomes)

Measure: Change in PGIS

Time: 10 Months

Description: 0 - 100 points (lower value represents worse quality of life)

Measure: Change in EORTC QLQ-C30

Time: 10 Months

Description: CTCAE version 4.0

Measure: Safety of Avapritinib as assessed by incidence of adverse events

Time: 10 Months

Description: h•ng/mL

Measure: Area Under Curve (0 to Tau) for Avapritinib

Time: 4 Months

16 A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy

This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

NCT03731260 Indolent Systemic Mastocytosis Smoldering Systemic Mastocytosis Drug: Avapritinib Drug: Placebo
MeSH: Mastocytosis Mastocytosis, Systemic
HPO: Mastocytosis

Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood. --- D816V ---

Primary Outcomes

Measure: Recommended Phase 2 dose (RP2D) in patients with ISM (Part 1)

Time: 9 months

Description: 0 - 120 points (higher value represents worse symptom outcomes)

Measure: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) in patients with ISM and SSM (Part 2)

Time: 12 weeks

Description: 0 - 120 points (higher value represents worse symptom outcomes)

Measure: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) in patients with ISM and SSM (long term, Part 3)

Time: Up to 5 years

Description: CTCAE version 5.0

Measure: Safety of avapritinib as assessed by number of adverse events (long term, Part 3)

Time: Up to 5 years

Secondary Outcomes

Measure: Change in serum tryptase

Time: Up to 5 years

Measure: Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood

Time: Up to 5 years

Measure: Change in bone marrow mast cells

Time: 12 weeks

Measure: Change in skin mast cells in patients with baseline mastocytosis in skin

Time: 12 weeks

Measure: Change in percent body surface area (BSA) involved by mastocytosis in skin

Time: Every 12 weeks during treatment through Week 52 of Part 3

Measure: Change in pigmentation of cutaneous lesions in patients with baseline mastocytosis in skin as assessed by skin photography

Time: Every 12 weeks during treatment through Week 52 of Part 3

Measure: Change in best supportive care (BSC) concomitant medication usage

Time: Up to 5 years

Description: 0 - 100 points (higher value represents worse symptom outcomes)

Measure: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)

Time: Each study visit through Part 3 Week 52

Description: 0 - 10 points (higher value represents worse symptom outcomes)

Measure: Change in Patient's Global Impression of Symptom Severity (PGIS)

Time: Each study visit through Part 3 Week 52

Description: 0 - 100 points (higher value represents better symptom outcomes)

Measure: Change in 12-item Short Form Health Survey (SF-12)

Time: Each study visit through Part 3 Week 52

Description: 1 - 7 (higher value represents worse symptom outcomes)

Measure: Change in Patients' Global Impression of Change (PGIC)

Time: Each study visit through Part 3 Week 52

Description: 0 - 100 (higher value represents better symptom outcomes)

Measure: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L)

Time: Each study visit through Part 3 Week 52

Description: CTCAE version 5.0

Measure: Safety of avapritinib as assessed by number of adverse events

Time: Up to 5 years

Description: h•ng/mL

Measure: Area Under Curve (0 to Tau) for avapritinib (Parts 1 and 2 only)

Time: Every cycle (28 days) up to cycle 4

17 A Phase 2 Randomized Double-Blinded Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in Subjects With Indolent Systemic Mastocytosis

Background: Mast cells help the body fight disease and heal wounds. People with indolent systemic mastocytosis (ISM) make too many mast cells. This causes pain, tiredness, digestive problems, and other symptoms. Researchers think the drug sarilumab could help. Objective: To see if sarilumab is a safe and effective treatment for people with ISM. Eligibility: Adults ages 18-75 with ISM who are enrolled in NIH study 02-I-0277 Design: Participants will be screened with: - Physical exam - Medical history - Blood and urine tests - Questionnaires - Bone marrow removed by a needle inserted into the hip bone - Ultrasound of the abdomen - Photographs of the skin Participants will repeat some screening tests at study visits. Participants will have a baseline visit in the hospital for 3 days. They will: - Be assigned to get either the study drug or a placebo. They will not know which one they get. - Have a skin punch biopsy: An instrument will remove a small piece of skin. - Get their first drug dose injected under their skin Participants will keep a side effect and medication diary during the study. Participants will visit the clinic to get a drug dose every 2 weeks, for a total of 8 doses. Participants will have a visit 2 weeks after their final dose. It will last up to 2 days. Participants will have another visit 12 weeks later. Participants may then continue this study for 1 more year. Those who continue will get sarilumab, even if they previously got the placebo, every 2 weeks. They will have visits every 6 weeks, and then every 3 months.

NCT03770273 Indolent Systemic Mastocytosis Biological: Sarilumab Other: Placebo
MeSH: Mastocytosis Mastocytosis, Mastocytosis, Systemic
HPO: Mastocytosis

Mastocytosis Quality of Life Questionnaire (MC-QoL).. QoL at 16 weeks post-initiation of study drug/placebo using the Mastocytosis Quality of Life Questionnaire (MC-QoL).. mast cells in bone marrow and allelic frequency of D816V. --- D816V ---

Decrease in the allelic frequency of D816V using PCR. --- D816V ---

Primary Outcomes

Description: frequency and severity of adverse events during the randomized double-blinded placebo-controlled treatment period

Measure: Frequency and severity of adverse events (AEs)

Time: day 0 through week 28

Description: QoL at 16 weeks post-initiation of study drug/placebo using the Mastocytosis Quality of Life Questionnaire (MC-QoL).

Measure: Mastocytosis Quality of Life Questionnaire (MC-QoL).

Time: 16 weeks post study drug initiation

Secondary Outcomes

Description: Reduction of percentage infiltrating mast cells in bone marrow. Decrease in the allelic frequency of D816V using PCR

Measure: mast cells in bone marrow and allelic frequency of D816V

Time: Day 0 and Week 16 for bone marrow and Day 0, week 16 and week 28 for D816V allelic Frequency

Description: Percent improvement in QoL using MC-QoL, scoring of mastocytosis index (SCORMA), and Memorial Symptom Assessment Scale (MSAS) and the Mastocytosis Quality of Life Questionnaire (MQLQ), and the mastocytosis Symptom Assessment Form (MSAF)

Measure: Questionnaires MC-Qol, MSAS, SCORMA, MQLQ, MSAF

Time: Day 0 through Week 28

Description: Reduction in use of medicines for symptomatic relief, reduction in serum levels of tryptase

Measure: Reduction in use of medicines and reduction in serum Tryptase

Time: Day 0 through Week 28


HPO Nodes


Mastocytosis
Genes 8
KIT ASXL1 KIT TET2 KIT KIT KIT SRSF2
Neoplasm
Genes 1473
GPC3 LETM1 LZTS1 REST MPL ARID1B RPL18 MGMT GLI3 BIRC3 ZSWIM6 TRNS2 ETV6 HNF1B KIT BRCA1 SUFU PLAG1 SOX9 TP63 CTSC RASA1 ATRX TRIM37 SUFU BTK CYP11B1 NOTCH3 EPCAM PORCN PIGL AR TET2 FH TGIF1 HMBS ATRX TREX1 SMAD4 KRT17 FGFR1 WDPCP SF3B1 GPR101 KIT GLI1 SLC25A11 XRCC4 SDHD PRKCD RNF43 SDHB BAP1 EGFR PIGA NF1 ASCL1 MPL RET C2CD3 GDNF NR5A1 DICER1 TNFRSF4 CASP10 TERC FGF8 PSAP CIB1 SLC22A18 PTCH2 ENPP1 CDKN2C SLC25A11 GPR101 KIT AXIN2 TREX1 DYNC2LI1 ERCC4 RPS14 COMP TINF2 FOXE1 DHCR24 RPS7 TYROBP HOXD13 ERBB2 BLK EYA1 ZFPM2 ERCC6 NLRP1 STAC3 ERCC5 NUTM1 MEN1 WT1 BCL10 GNPTAB KRAS TP53 KDR PUF60 TRNF FCN3 SDHC KCNH1 MSTO1 EP300 BUB1B GNA11 KCNE3 DOCK8 SEMA3C ACD GLI2 SMPD1 SUFU NF1 PTCH2 ACAN DCC WT1 CTSA KIF11 BCR SRGAP1 KIT PTEN LEMD3 MLLT10 SCN4A BRCA2 BMPR1A NOTCH3 SEC23A CDKN1C BARD1 SPIB RSPO1 MC2R CALR ATP6V1B2 NBN RAD54L MST1 SUFU MYCN TMEM127 SRD5A3 IGF2 CD28 RUNX1 OGG1 HAX1 SDHC CTNNB1 MST1R SDHA IGF2 KCNJ10 IL12RB1 MEN1 RAD51 TFE3 ND5 MMEL1 MVK APC FLI1 RNF6 NF1 BRCA2 SUFU GPC6 NR4A3 TTC37 KIT NRTN BLNK IGH SPRED1 TXNRD2 IGF2R FOXP1 BUB1B SOS1 LRP5 GJB2 DNMT3A PMS2 PRKN RET MSH6 ACVRL1 MPLKIP ERCC2 AIP GNAS TAL1 NNT RECQL4 PMS1 DLL1 EIF2AK4 STAT6 MNX1 SDHB KRAS MEN1 MN1 SH2B3 EFL1 VHL KLLN RMRP RUNX1 SIX3 GDNF FANCD2 EXT1 CDH23 BRD4 DLEC1 NODAL CARMIL2 SDHB MSH2 HMBS SMAD4 SRP72 NRAS DOCK8 SPRTN BRCA1 MAP2K1 KRT14 LETM1 TERT MAP2K2 HRAS WHCR WT1 IDH1 TMEM107 SCN10A GJB3 SDHD KRAS GATA1 RPS20 GJB2 SLX4 USP8 PRKAR1A CR2 JAK2 HFE MPL POT1 BRCA2 GNAI3 SDHB ALK OCA2 TP53 GPC4 ACTG2 CTNNB1 HSPG2 AR FGFR1 STK4 MET TMC8 MRAP MSH6 CCBE1 EWSR1 LMO1 EDN3 LEMD3 PGM3 FGFR3 CASP8 RB1CC1 SCN9A FANCL TG SDHD COX3 IGF2 COL11A2 AGGF1 GPR101 PRKN PLCB4 SDHD NF1 GTF2E2 MAP2K1 ESCO2 CDC73 WRAP53 TET2 PDGFRB RNASEH2A RAD21 HNF1A TGFBR2 POLD1 COX2 TNFRSF10B MINPP1 DNAJC21 FAS EXT1 SLC26A2 APC SDHAF2 TINF2 LIG4 POLR1D WWOX TMC6 RPS19 ERCC2 SASH1 MC1R MVD SEC23B CYP2A6 GPC3 KIT HRAS RAD54L SDHA GDNF NKX2-1 GFI1 ALX3 STAT3 MYH11 DYNC2LI1 FGFR2 TCOF1 PTEN MAFA PIK3R1 SLC25A13 HRAS VHL COL7A1 GNAS FGFR2 PIK3CA GPC4 DICER1 ERCC3 PIK3CA RAD51C RB1 RMRP MLH3 ATM COL7A1 LIG4 NF1 VAMP7 RPL35A RB1 SETD2 BCL10 LPP NRAS KRAS ABCA5 ERCC2 PDE6D KCNQ1OT1 MS4A1 SLC22A18 APC LIG4 JAK2 FANCD2 GAS1 STAG3 NRAS PALLD SLC22A18 RFWD3 PPP2R1B APC PTPN11 PTEN WIPF1 PIK3CA NOP10 IL7 UROD TNFRSF1B TP53 REST SLC37A4 NHP2 CXCR4 KIT CYSLTR2 FZD2 ALX4 BMPR1A SRY TRNQ SDHD PIGL CCM2 FIBP FANCI GJB4 SPINK1 RPL10 NSD2 MAP3K1 RET CDK4 HSPA9 TET2 GFI1B MAD2L2 DCC AP2S1 SMAD7 BRCA2 TRNK ERCC3 BRCA1 ELANE SFTPC PTH1R COL1A1 FUZ OFD1 RET FLT4 PRKAR1A SBDS RPL26 SMARCE1 SMARCAD1 MSH2 BCR GPR35 INTU FANCA STAT1 ANTXR2 FGFRL1 TUBB BRAF SLX4 CASP10 TERT RAD21 MTOR TRIP13 MYD88 DPM1 RSPO1 PTPN11 CTNNB1 AIP PTEN VANGL1 CYP2D6 RPS10 GCK KRT16 DNAJC21 BCL2 AKT1 KRAS KLF6 NOTCH1 FLNA MAX NF2 PALB2 TP53 PSENEN RNF6 TSC1 HNF1B TP53 RFWD3 SDHD PERP TP53 DIS3L2 B3GALT6 STS PDGFB SMARCB1 BRAF BRIP1 CBFB BUB1 BLM INHBA CALR NBN MLH3 TAF1 MLF1 PIK3CA MSH2 CTLA4 ND6 PALB2 WT1 PTCH1 POLE ADA MC1R FLT4 ATP7A MLH3 SMO TRNF NRAS LMNA DLST TRNL1 MTAP TP53 ZAP70 SDHB CHEK2 PALB2 FLT4 CDK4 NBN MSR1 CC2D2A TNPO3 ECE1 RPS15A NAGS TMEM67 HNF1A PIK3CA ATP7A AKT1 NRAS SDHAF2 CXCR4 TSC2 NF2 EPHB2 WDPCP OFD1 BUB1 FLT3 APC SMARCA4 CDKN2A RPS29 MCM4 PDGFRA ESCO2 CTC1 ESR1 SDHB MSH6 APC HABP2 GNAQ KIF1B SH3GL1 CD70 MPL IGH ZIC2 GCM2 VEGFC HRAS CTNNB1 KCNH1 LRRC8A BRAF FAS ICOS NSD1 RNF43 AKT1 BIN1 DLC1 SH2B3 RARA WNT10A CARD14 SDHC EXOC6B ESCO2 POLR1C G6PC MSH6 KRT1 PDX1 TNFRSF13C ERCC3 EVC SNAI2 CD79A BRCA1 RNASEH2B CCND1 TP53 RPS19 H19 H19 BRCA2 TFAP2A ARMC5 FASLG FGFR3 APC F5 EDN1 MAP3K8 AIP APC AKT1 TERC CCND1 CEL MYC TP53 GPC4 ERCC5 HNF1A POLE DAXX NUP214 TRIP13 AKT1 TET2 CDC73 ND1 MUTYH PIK3R1 TERT CEBPA EXT2 OCRL DIS3L2 ADAR TGFBR2 BRCA2 MRE11 SOS1 HNF4A FAH TMEM127 WT1 AXIN2 TCF4 EDN3 PTPN3 KRAS SEMA4A PIK3CA XPA MFN2 TINF2 PIK3CA APPL1 RUNX1 GNPTAB FGFR3 NRAS PDCD10 RAG2 PTEN CTNNB1 SOX2 BMPR1A HBB TERT USP9X NFKB1 FANCC PRF1 WRN SRY SRSF2 PMS2 RHBDF2 PHOX2B RPS17 PAX3 RECQL4 KIF1B SQSTM1 RB1 EXT1 XPC CYLD TOP2A MYD88 CDKN1B TET2 GJB2 PTEN UBE2T RTEL1 PTCH1 KLHDC8B GATA1 POLH JAK2 RHOH FLCN DCLRE1C MTMR14 GTF2H5 PTEN SBDS TBC1D24 PAX7 AR TP53 ASPSCR1 MTM1 RECQL4 ERCC2 TGFBR2 ERCC4 JAK2 SF3B1 CDKN2B XPC GATA4 KIT POU2AF1 BRCA2 GREM1 CDON NTHL1 DICER1 GINS1 ATM RAD51D SHOX EXT1 RASGRP1 WT1 GATA2 NF2 ERCC4 TUBB MBTPS2 DHCR7 MYLK KCNN3 TCTN3 TMEM216 TMEM231 KRT1 CTNNB1 MPL PDGFRB FANCG RPGRIP1L KEAP1 DICER1 WT1 BAP1 FOXI1 ERCC4 CDKN2A FGFR3 KDSR CBL HRAS BMPR1A DISP1 RELA MAP3K1 PARN BCR ENG COL7A1 LMOD1 KRAS PAX6 SNAI2 GLI3 FANCF FOXO1 RPL15 TBX18 TRPV3 PIK3CA NRAS CDH1 GNAS SMARCB1 KLF11 ADA2 EDN3 POU6F2 CDH1 GNAS IL1B SMAD4 H19-ICR SDHB STK11 NF2 TRIM28 SEC23A SLCO2A1 BRCA2 BRAF DNMT3A MDM2 BMP2 BRCA2 DHH NRAS POU6F2 CTBP1 PTCH2 FLCN CALR BAP1 LIG4 HRAS REST BRAF SAMD9 NDP TYR KRT17 MUC5B PRSS1 MEN1 NPM1 ITK MSH2 CYLD TAL2 SRP54 IFIH1 HMMR TCTN3 ND5 JAK2 FAM20C RET NEK9 DMRT3 KRAS MINPP1 SH3KBP1 THPO FAH KRT5 JAK2 PHKG2 TSC1 TNFRSF13C MEN1 FH RPL31 FANCG PIK3CA IL2RG DNAJC21 VANGL2 MYO1H ALX1 CDKN2A AIP H19 NRAS TWIST1 PTEN TRNK TRPS1 RPS26 MAPRE2 RPS27 TCF3 KRT17 ERCC6 DHH MMP1 FGFR1 SEMA3D PTCH1 ABL1 CDKN2A SKI APC WWOX ZSWIM6 NF2 WNT10A KRAS GPC3 REST GJB6 HRAS VHL CTNNB1 TGFBR1 IL6 TDGF1 RPL11 IL1RN BRCA1 MGAT2 POT1 ASCC1 XPA TBX2 FLCN HFE NTHL1 SMARCB1 DVL3 TRNH IDH1 FANCA LAMB3 CD79B RAD51C PRDM16 PHOX2B GNAQ CCL2 PDGFRA CREB1 SRP54 PIEZO2 TRNL1 GBA GNAS WNT5A PIK3CA STS FANCB KRAS MAGT1 RAD51 IDH1 TNFRSF13B TREM2 GABRD BCL10 SKIV2L POLD1 KRIT1 KRAS ARSA SMAD4 RAD51 TP53 DIS3L2 KIAA0753 PRLR CD96 LZTR1 WRN GATA2 EDNRB MUTYH ATM CHIC2 TP53 CYLD PAX4 SLC26A4 RTEL1 VHL NEK1 TRNS1 GCM2 TYR ATP7B CTHRC1 BRAF ASXL1 OFD1 MLH1 CDKN1A PHOX2B XRCC2 CD19 RB1 FOXC2 TRIM28 EWSR1 TERT GNA11 F13B CDKN2A KARS1 BCL10 TP53 WT1 CDKN2A FDPS KIT COX1 COL14A1 VHL WT1 TERT SMAD4 STAR NUMA1 RPL5 PDGFB PCGF2 CFTR KCNQ1OT1 KIT GJA1 GNAQ CD27 FANCC IDH2 EVC2 BRCA2 TCF4 KRAS PIK3CA CDC73 ACVR1 BRIP1 TRNW PRCC GCGR CDKN1B STK11 SCN11A TGFBR2 AXIN2 ERBB2 RPL35 APC TSC2 IL12A SSX2 TET2 KIF1B DICER1 TRNP BTK CCDC22 PDGFRA ALX3 ADAMTS3 CD81 RET DKC1 GLI3 FGF3 SMAD4 STK11 ERCC6 WT1 ELANE C11ORF95 SAMD9L SLC45A2 NQO2 PTPN11 ATR PDGFRL TNFSF12 BRCA2 ADA BUB1B FASLG GDF5 KRAS CPLANE1 CREBBP CDC73 CLCNKB GATA2 CTRC SDHA ACTB APC BMPER SPINK1 APC2 MC1R FOXI1 DYNC2H1 KIT PPM1D SDHC NSD1 SDHC DDX41 ANTXR1 CASP8 F13A1 SUFU INS NUP214 ANTXR2 KIF7 NFKB2 ABCC8 TARS1 ERCC3 TCIRG1 ND4 ERCC2 GNAS TERT WASHC5 SLC49A4 RERE CALR MSH3 PHOX2B SLC25A13 BMPR1B CYLD SIX6 ASCL1 IDH2 FAN1 CHRNG CBL NEUROD1 MSH3 THPO VANGL1 CDKN2B TAF15 PTCH2 HMGA2 MSH6 CHEK2 FN1 GATA2 IRF1 KRAS BMPR1A NPM1 ERCC3 CDH1 ALK DNM2 ERBB3 PTPN11 DLST MUTYH PARN GFI1 NBN FGFR3 CHEK2 EP300 RNF113A TNFSF15 TEK TERF2IP ICOS COL18A1 TNFSF12 BRAF CHEK2 IFNG TMC6 USB1 KDM6B GJC2 SLC26A2 MDH2 TP53 ENG MLH1 KRT6B MNX1 PDGFB TRNH POLE CASP10 HPGD TET2 RB1 PHOX2B JAG1 GNB1 ACD TNFRSF13B MYC BRAF TSC1 SAMD9L BCL10 H19 POT1 USP8 IGF2 OFD1 CYP11B2 KCNQ1 CDH1 LMX1B TET2 ANTXR1 JAK2 SMARCB1 ELMO2 PTCH1 SIX1 L2HGDH WRAP53 BUB3 AXIN1 RET KCNJ11 ABL1 FANCE RAD54B FANCM TSC2 MAX IGHM TSC1 HACE1 CASR RNF139 MITF RAF1 WT1 TCTN3 POLH LIG4 TP53 KRT10 AAGAB SRY RAD50 TNFRSF1B TRNQ DNASE1L3 FAM149B1 KRT9 VHL FLCN TBXT SLC37A4 DKC1 PNP DDB2 SETBP1 ECM1 MSH2 CR2 COL2A1 COL7A1 MLH1 FH SFTPA2 PIK3CA FOXH1 MET HNF4A H19 KAT6B GPR143 PHB PMS1 ATP7A FAT4 TJP2 TFAP2A GDF2 AHCY TSC2 CD19 TRNS1 BDNF TRIP13 AKT1 FGFR2 RAG1 BRCA1 SDHC MLH1 XRCC3 NSD2 LMNA SDHC TERC EXT2 PIK3CA MSH3 SDHD SRC CHEK2 C1S ABCA5 HBB RYR1 FGFR2 CDC73 KIT FANCE RET LYST KCNJ10 BCHE HDAC4 INPP5E CRKL PHOX2B BAP1 CPLX1 PDGFRB ARL6IP6 RNASEL SETBP1 CTLA4 PALB2 DCLRE1C NSUN2 XIAP TRNS2 BMPR1A IL7R BCL6 COL4A5 PIK3CA NOD2 PRKAR1A NELFA IL2RG MYH8 RHBDF2 IGLL1 PIK3CA SERPINA1 FOXE1 ARHGAP26 TCF4 MITF ABCB11 ERBB2 GNA14 SLC26A2 NSD1 SH2B3 STK11 PTCH1 GDNF RPL27 DHCR7 WAS CIB1 SHH CACNA1S LIN28B SF3B1 ATM PRKCD RPS24 LAMA3 ATRX CASP8 AKT1 OPCML HFE SH2D1A ING1 CCND1 SLC12A3 HABP2 H19 LAMC2 RAD51C NAB2 NRAS MAPK1 CPLANE1 CYP26C1 CDKN1B CHD7 IGH MYF6 BLM ASXL1 FH NEK1 HLA-DRB1 SLC26A4 RPS14 SHOX RNASEH2C SMARCD2 GATA2 CDH23 WT1 EPCAM NR0B1 KLLN DVL1 SEC23B GPC3 SLC17A9 BRCA1 SRP54 DKC1 RECQL4 CD28 PTPN11 HRAS NBEAL2 BARD1 MLH1 DDB2 PMS2 IRF1 ABCC6 EXT2 ASXL1 TSR2 PTEN MALT1 PTEN BCR PALB2 BRIP1 SSX1 PHKA2 FGFR2 SDHB FERMT1 KCNAB2 FLT3 PMVK MSTO1 CEP57 MMP1 PICALM IRF5 TP53 PTPRJ RNR1 WWOX PLCD1 RPS28 FGFR3 COL2A1 IKBKG TERT RASA1 SAMHD1 PHF21A
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Juvenile myelomonocytic leukemia
Genes 7
NF1 ARHGAP26 CBL CBL KRAS PTPN11 NRAS
Anaphylactic shock
Gastrointestinal stroma tumor
Genes 25
PDGFRA CD19 SDHB KIT CD81 SDHC PRKCD SDHB TNFRSF13B TNFRSF13C MS4A1 NFKB1 KIT NFKB2 SDHA SDHC TNFSF12 SDHC CR2 ICOS TNFSF12 SDHB SDHB SDHD KIT
Chronic myelomonocytic leukemia
Genes 4
KIT ASXL1 TET2 SRSF2