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 Eosinophilic Myeloid Neoplasm 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)

Description: Including morphologic complete remission (mCR), morphologic CR with partial recovery of peripheral blood (mCRh), and morphologic partial remission (mPR) based on Pure Pathologic Response

Measure: Morphologic response

Time: ≥ 12 weeks

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 Leu 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, Sys 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


HP:0002664: Neoplasm
Genes 1489
WHCR ATP7A PHOX2B KRT17 IL2RG HMGA2 PORCN KRAS TET2 IDH2 FLT3 ERCC4 AR BRCA1 BRCA2 GATA1 TCF4 TCTN3 GPR101 SMAD7 KRT6B PIK3CA KCNJ10 MAP2K2 REST TTC37 MC2R TRPS1 SIX6 ALX4 PIK3CA BRAF TP53 STK11 TSR2 EXT2 EDN1 RNF43 TRNL1 ATM SDHC EXT1 BCL10 BAP1 NF1 OCRL TP53 CHD7 TINF2 ERCC6 NF1 MAFA PMS2 ASXL1 PHOX2B CTNNB1 CR2 RET TCTN3 C11ORF95 PTPN3 PIEZO2 ABCB11 SETBP1 PDCD10 LRP5 LMOD1 MALT1 ASXL1 LZTR1 TINF2 RAD51C RECQL4 MAP2K1 FOXO1 PTCH2 RPS20 FLI1 BMPR1A SMARCAD1 BMPR1A MAP3K8 DNASE1L3 SUFU TP53 FOXP1 PTCH1 PDGFRB ND1 PIK3CA ZSWIM6 SETD2 INS NRAS HBB MEN1 AIP CLCNKB RPS10 HFE COX2 TSC2 DHH CTRC MEN1 EYA1 BRCA1 GINS1 MSH3 GLI2 TRNS1 HABP2 SSX1 SUFU PRKN CD81 TNFSF12 MYH11 KIT VEGFC WWOX H19 SDHD FGF3 TNFRSF1B RMRP XRCC2 HRAS MTM1 EPHB2 PLCD1 NBN CDKN1B TUBB RECQL4 EDNRB VHL ACAN MSH6 CDKN2B DCC TJP2 HRAS CDKN2A VHL REST NKX2-1 ANTXR1 RPL35 DNM2 FGFR3 SNAI2 NLRP1 ACTG2 GNB1 EWSR1 CBFB NSD1 FLCN ERBB2 MLH1 H19 EIF2AK4 RPL10 TMEM107 TRNK RAD54L RAD51C INPP5E NFKB1 CDKN1A KDM6B F13B SLC26A2 TRNS1 RPL26 CYLD H19 PTEN PTPN11 DCLRE1C MPL FLCN NEK1 MITF MSH3 NUTM1 IL7 STAT3 TRNS2 TG ERCC3 MNX1 NRAS MLH3 TSC1 GLI3 CDK4 SDHC NF1 BRCA2 CIB1 ATRX BRCA2 ADAMTS3 ZFPM2 COL2A1 TET2 ZIC2 SLCO2A1 BLM GJA1 MAP3K1 PIK3CA SDHA RTEL1 CDK4 KCNH1 SH2B3 APC ESCO2 FANCC TERT USP9X APC RAD54B NF2 SDHB RPS14 PPP2R1B RPS19 RPL35A MSH2 WRAP53 RASA1 LMNA ACVRL1 POLH SDHB DIS3L2 PIGA GNPTAB CXCR4 MSH2 SLC25A13 BMP2 NNT PSENEN FOXI1 APC IL1RN MITF ACD PTEN MPL RUNX1 ERCC3 ERCC4 DLEC1 CHEK2 BRCA2 JAK2 SBDS BRCA1 SDHD SEMA3D MSH6 HFE TREM2 APC CCDC22 MINPP1 DISP1 FAM20C MAP2K1 ALK BRCA1 STIM1 SLC25A13 RFWD3 HRAS GLI1 TET2 DVL3 COL7A1 HMBS TFAP2A ICOS CALR PTEN UROD DKC1 FDPS LIG4 TXNRD2 SRSF2 ND5 SDHD CHEK2 NRAS BCL6 GPC3 XPC MEN1 ERCC2 AXIN2 MYC RAD51 GBA KIF1B SDHB EXT2 EXT2 NTHL1 SRY RPGRIP1L MPL MTOR CASP8 RB1CC1 IGF2 FANCC ERCC4 WRN PGM3 VHL ING1 PLAG1 WT1 MYLK KLLN PIK3CA G6PC RPS7 MCM4 ANTXR1 POLH BRCA2 DLL1 OGG1 WRN F13A1 SBDS EFL1 TAF15 GLI3 GPC3 KRAS CDKN2B MAPK1 DIS3L2 GPR101 NRTN DKC1 KLLN NSUN2 MAP3K1 ERBB2 PHKG2 SRGAP1 CYLD NBN ALK MAX WT1 ACTB PALB2 TBX18 FIBP CASP10 DVL1 TYR MSH2 RECQL4 PIGL EDN3 WT1 ATP7B RPL27 RET USP8 FGFR2 PDGFRL H19 CCND1 ATM AXIN2 COL7A1 AKT1 TERT MUTYH HOXD13 DICER1 THPO GDF5 CEL SDHB EXT2 SRP72 TERT TRNF TP53 LIN28B APC NPM1 FGFR3 PTEN SMPD1 SLC22A18 SDHC PRDM16 KIT STK11 RPL11 LETM1 CALR SDHC RB1 PIK3CA PLCB4 COL4A5 CASP8 SKI H19 COL1A1 CC2D2A CASP10 GCGR GLI3 PIK3CA RPS29 RSPO1 PTEN MYSM1 BAP1 SRY UBE2T BRCA1 USP8 COL7A1 RNASEH2B KIF1B MN1 RELA SMAD4 VHL SH3KBP1 BCR CD79B SRP54 SRP54 SSX2 CHRNG RPL18 NF1 WWOX RERE LZTS1 WT1 MSH3 TYROBP ASCL1 IKBKG ABCC6 FAH KIT GDNF FANCE TERT BIN1 FANCL KIF11 SDHB WDPCP SLC6A17 TP53 HNF1A KEAP1 POLE HSPA9 SMO PTCH2 PTCH1 PMS1 ELMO2 BCL2 NSD2 EXT1 SRD5A3 STAT6 MVD TERC SF3B1 MNX1 FGFR1 CYSLTR2 POU2AF1 SMARCB1 NOD2 GJB2 SDHC FLT4 KRT9 CDH1 IRF1 SEC23B MYCN MGMT RPL10 RPL5 KIF7 TCF3 KRAS MUTYH TMEM127 KRAS IGH CTSC GNAS CD28 WWOX HNF1A BUB1B MC1R WNT10A CBL WT1 BRAF ADAR GAS1 GTF2E2 SMARCB1 RPS17 PARN TMEM127 BRIP1 SHH SRC GNAI3 STAR GDNF SLC22A18 FOXH1 SNAI2 GPC4 TNFRSF13C KARS1 TBC1D24 BMPR1A TET2 CD27 CASP8 DHCR7 KDSR HNF1A SH3GL1 PNP USB1 TSC2 TRIP13 TMEM67 EDN3 PMS1 PTPN11 GNA11 CREB1 ADA RAG2 PRSS1 KCNQ1 GPR101 PRF1 MTAP FANCA MSH6 TRNQ BRCA2 KRT1 RNASEL POU6F2 ACD SCN9A APC NSD2 INTU BRAF POU6F2 BRCA2 RB1 GTF2H5 PIK3CA FANCM TARS1 BRAF CASR RET VHL GPR143 TRNP GCM2 TMEM231 CPLANE1 RPS15A SOX9 GFI1B EPCAM MEN1 TERT KRAS SDHAF2 NF1 TRIP13 GATA2 SLC26A4 APC MPLKIP SAMD9L IL6 GNAS IGH AKT1 FANCD2 ESR1 SDHA APC MYF6 RASGRP1 SMAD4 MLLT10 LIG4 CPLANE1 BRCA2 MC1R MRE11 DLST SUFU LMO1 SDHB ABCA5 RMRP SDHC NUP214 AKT1 SMARCD2 DLC1 C1S TRNW THPO CHEK2 KIT SLC37A4 BCHE KCNJ11 ARID1B APC2 SAMD9 TMC6 SLX4 TNFRSF13B FGFR1 TRNH RAD21 KCNN3 DKC1 VANGL1 AXIN2 TCOF1 RPS19 SLC26A2 GPR35 CR2 TFAP2A KRAS FGFR3 PRKCD JAK2 EGFR AIP CTNNB1 KCNJ10 FANCI LYST TET2 SLC25A11 TP53 TCTN3 MUTYH ANTXR2 SEMA3C MMP1 AKT1 PDX1 JAK2 TCIRG1 PTCH1 MUC5B EXT1 DNMT3A BMPR1A SERPINA1 FAN1 CDC73 PTCH2 PIK3CA H19 FERMT1 GPC3 RET RET APC PALLD LPP BRD4 GNAS BMPR1B MAPRE2 DICER1 CTC1 TAL1 DICER1 STK11 HRAS GATA1 BCL10 KCNE3 XRCC4 HNF4A BDNF KLF11 SF3B1 MLH3 GNAQ TRPV3 IGLL1 PAX7 CRKL GDNF GATA2 ARL6IP6 ENG PTCH1 NEK9 TSC1 RNF139 ERCC3 PDGFRA IL2RG CTHRC1 WT1 BAP1 ATP7A SRP54 ABCC8 ESCO2 GPC4 OFD1 TNFSF15 APPL1 RNF6 CTSA TNFRSF1B TP53 PHOX2B DCLRE1C DDB2 BCL10 BCR KRT14 ALX3 EVC2 CD70 SMARCB1 AHCY SDHAF2 RAD51D SPINK1 SDHD ATM GABRD WT1 FASLG CTBP1 NOTCH1 NF2 DPM1 ERCC6 STS PHOX2B BUB1 FLT4 L2HGDH LAMC2 NTHL1 STAG3 ENG SDHD CTNNB1 DAXX NRAS MST1 MSTO1 SLC26A4 RAF1 STS FGFR3 EXOC6B VAMP7 NELFA HRAS ANTXR2 LEMD3 TNFSF12 GPC4 MLH1 SMAD4 RAD50 SUFU TRIP13 REST GNAS CBL RHBDF2 ASXL1 SMAD4 TCF4 ERCC6 WT1 BRAF APC TRIM28 TERT DNAJC21 RPL15 PAX3 SETBP1 CDH1 GNAS SMARCB1 AKT1 ASCL1 KRAS NAB2 ERCC5 RECQL4 KRAS DNMT3A EDN3 POLD1 FAM149B1 CDKN1C KRAS TP53 SMARCE1 PTEN PALB2 SEMA4A TEK NBN NHP2 GPC3 ETV6 FGF8 COL11A2 SMAD4 RNASEH2A NRAS MC1R TDGF1 FGFRL1 FGFR1 CTNNB1 IGH DNAJC21 CCND1 RET DIS3L2 DHCR24 CARD14 BRCA2 SQSTM1 NFKB2 TRNQ NDP SFTPA2 PAX4 COL7A1 TP53 RSPRY1 IFNG HMMR PALB2 FAT4 MBTPS2 MDM2 KRAS GNAS C2CD3 POT1 ABL1 WNT5A FANCE ABL1 ICOS SDHD RAD21 NSD1 SOS1 IL12A LIG4 PIK3CA TBXT RAD51 EWSR1 FZD2 FLNA BRCA2 NRAS TWIST1 TET2 TSC1 INHBA CAT CTNNB1 PIGL IRF1 PTCH2 TRNH MLH1 GFI1 CDC73 RET FANCD2 EVC NF2 TNPO3 SOX2 DYNC2H1 HRAS NEK1 CCND1 KRT10 AKT1 KIT PALB2 VHL CYLD IL1B GJC2 MLH1 SDHC FGFR2 CYP2A6 FOXE1 ARMC5 ERCC2 SLC25A11 LAMA3 FLCN BRCA1 BIRC3 MVK TOP2A PDGFB TCF4 RFWD3 ATP6V1B2 GDNF GATA4 CTNNB1 CDKN1B C2CD3 BRCA2 FUZ STK11 AKT1 FGFR2 SHOX TGFBR1 BTK LEMD3 FIBP SF3B1 SUFU PRLR NR5A1 FN1 ERBB2 CD19 RNR1 PTPN11 KIT RAD51 WAS PTEN TGFBR2 RPS24 CYLD RNF113A MYO1H ALX3 JAK2 BLM CTNNB1 CDKN2A PARN SH2B3 POLD1 CHEK2 COX1 KRT1 EXT1 BRAF PRCC MSH2 GATA2 REST NRAS RB1 TINF2 BMPR1A NR4A3 AGGF1 SIX3 RAG1 ND4 COL2A1 CDKN2A SDHD TREX1 WNT10A SEC23B XPA MET TP53 CDKN1B RPS27 PCNA HMBS RPS26 KIT FGFR2 TRIM37 HPGD ERCC5 PAX6 SLX4 PICALM PSAP FCN3 BMPR1A USF3 XPC DNAJC21 KRT16 BUB3 H19-ICR GPC6 STAC3 RPS28 FANCA RNF43 AP2S1 PDGFB DYNC2LI1 CYP11B1 ABCA5 PTCH1 TERF2IP KRAS DYNC2LI1 CDH1 CDC73 TERC SPRED1 PDGFB TRNF MTMR14 MAD2L2 FOXI1 ERCC2 GJB4 KAT6B MSH6 FASLG KRAS SEC23A RUNX1 CD19 WASHC5 KIT HLA-DRB1 WRAP53 FLT3 CEP57 KDR TREX1 TMEM216 PDGFRA ERCC3 KIT NOTCH3 WIPF1 TERC CTLA4 NQO2 CDKN2A RSPO1 STK4 PTPN11 GJB2 KRAS MET SPINK1 PDGFRB RHOH BUB1 ND6 CDKN2C TFE3 EP300 CHIC2 HNF1B NUMA1 BRCA1 SRY FLCN MLH3 SCN10A GNPTAB KRAS NODAL TGFBR2 PPM1D DOCK8 EPAS1 PHOX2B OCA2 KCNQ1OT1 CYP2D6 ITK DICER1 PRKCD ASPSCR1 SUFU IDH1 RUNX1 ATRX FOXC2 MFN2 SAMD9L SCN4A KIF1B DHH POLE VHL POLR1D KCNAB2 BRAF SLC12A3 CARMIL2 ENPP1 NRAS LRRC8A KIT SH2B3 MST1R CEBPA NRAS MRAP TP53 ND5 FH LAMB3 CALR SLC37A4 PERP KLHDC8B FH SFTPC TGIF1 CHEK2 SLC17A9 SLC22A18 TERT CDH23 MDH2 KRT17 PTEN FGFR3 RB1 YY1 ELANE EP300 SPRTN GJB3 XPA IDH2 MAGT1 ATR GNA14 OFD1 IL7R GREM1 ESCO2 HRAS PRKAR1A MMP1 TP53 KRT17 COL14A1 RHBDF2 MPL OFD1 RYR1 IFIH1 SCN11A IDH1 JAK2 WT1 TP53 ARSA LIG4 CCBE1 FANCG KCNH1 ELANE COL18A1 HACE1 NUP214 MYC CD79A AR CDH1 BRIP1 WT1 BCR BUB1B ERCC3 KRIT1 NBN IGF2 FANCF PDGFRA BLNK PCGF2 MSH6 MEN1 FAS BRIP1 PTH1R SIX1 RNF6 BRAF DHCR7 BMPER BUB1B TP53 RET CTLA4 HABP2 ARHGAP26 DLST GCK ERCC2 RAD54L POLE HSPG2 GNA11 ADA SMAD4 BCL10 RB1 STAT1 TAF1 RPS14 BCR IL12RB1 IRF5 TMC8 TNFRSF13B CYP26C1 CALR POT1 MINPP1 POLR1C CD28 ATP7A HNF1B ERCC2 ACVR1 RPL31 VANGL1 TP63 ERCC4 SLC45A2 OFD1 LMX1B PIK3CA ASCC1 TET2 IGF2R BARD1 TUBB IGF2 BTK MSTO1 CIB1 PHB CDKN2A TNFRSF10B KIAA0753 TBX2 FOXE1 EPCAM TNFRSF13C SLC26A2 ATRX MGAT2 SKIV2L CXCR4 PIK3R1 RTEL1 TSC1 HAX1 SDHB PRKAR1A DDB2 GFI1 CDH23 XRCC3 PMVK TP53 PIK3CA GJB2 NF2 KLF6 AR ZSWIM6 SDHB CDC73 PIK3CA CCND1 GJB6 ATM SOS1 NOTCH3 DDX41 TSC2 FLT4 FGFR3 RASA1 GDF2 F5 PMS2 PTEN HBB TSC2 CASP10 ADA2 AIP WT1 LETM1 PNP COMP TRIM28 TP53 PALB2 RAD51C CCL2 CDC73 SH2D1A COX3 ZAP70 PIK3CA CYP11B2 PDGFRB PTPN11 PHOX2B FH KIT HNF4A RNASEH2C MYD88 PDE6D JAG1 TYR SEC23A FH NPM1 PHKA2 DICER1 PIK3CA HFE GNAQ DMRT3 MS4A1 MYH8 VANGL2 SHOX PUF60 GATA2 BAP1 B3GALT6 TRNS2 HRAS HDAC4 FANCG SAMHD1 GATA2 LIG4 AXIN1 TNFRSF4 OPCML PRKN FGFR2 ECM1 TGFBR2 LMNA WDPCP KCNQ1OT1 BLK GCM2 ALX1 NRAS KIT AAGAB FAH MAX RARA NEUROD1 TGFBR2 MYD88 PHF21A IDH1 MLH1 FANCB CPLX1 SMARCA4 EXTL3 AIP TERT BCL10 XIAP IGF2 SASH1 PIK3R1 PTEN NAGS TMC6 NBEAL2 NOP10 JAK2 SDHB MSH2 ECE1 BARD1 APC PMS2 CCM2 JAK2 MMEL1 RET SDHA SDHD IGHM CACNA1S FAS NR0B1 POT1 SPIB TAL2 NF2 CDON WT1 TET2 PTPRJ CD96 TRNL1 DOCK8 DCC MPL GNAQ CREBBP CDKN2A TRNK MSR1 KRT5 PRKAR1A ERBB3