SNPMiner Trials by Shray Alag


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Report for Mutation F317L

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 7 clinical trials

Clinical Trials


1 A Randomized Multi-Center Open Label Study of BMS-354825 vs Imatinib Mesylate (Gleevec®) 800 mg/d in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to Iamtinib at a Dose of 400-600 mg/d

RATIONALE: BMS-354825 and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This randomized phase II trial is studying BMS-354825 to see how well it works compared to imatinib mesylate in treating patients with chronic phase chronic myelogenous leukemia that did not respond to previous imatinib mesylate.

NCT00112775 Leukemia Drug: dasatinib Drug: imatinib mesylate
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

DISEASE CHARACTERISTICS: - Diagnosis of chronic phase chronic myelogenous leukemia (CML), meeting all of the following criteria: - Less than 15% blasts in peripheral blood and bone marrow - Less than 20% basophils in peripheral blood - Less than 30% blasts and promyelocytes in peripheral blood and bone marrow - Platelet count ≥ 100,000/mm^3 (unless thrombocytopenia is due to recent therapy) - No extramedullary involvement (other than liver or spleen) - Philadelphia chromosome (Ph)-positive disease by cytogenetic analysis - Must have developed resistant disease during prior treatment with imatinib mesylate* at a dose of 400-600 mg/day**, as defined by 1 of the following: - Loss of major cytogenetic response (MCyR) - Achieved a confirmed MCyR and subsequently no longer meets the MCyR criteria - Documented increase in Ph-positive metaphases by 30% on 2 cytogenetic analyses performed ≥ 4 weeks apart during treatment with imatinib mesylate - Loss of complete hematologic response (CHR) - Achieved a confirmed CHR and subsequently no longer meets the CHR criteria on all asessments over a consecutive 2-week period during treatment with imatinib mesylate - Continuously increasing WBC count on ≥ 2 consecutive evaluations ≥ 2 weeks apart with the final assessment showing a doubling of WBC from the nadir to ≥ 20,000/mm^3 OR an absolute increase in WBC by > 50,000/mm^3 above the lowest count after starting imatinib mesylate - No CHR after 3 months of treatment with imatinib mesylate at a dose of 400-600 mg/day - No cytogenetic response after 6 months of treatment with imatinib mesylate at a dose of 400-600 mg/day - No MCyR after 12 months of treatment with imatinib mesylate at a dose of 400-600 mg/day NOTE: *Imatinib mesylate does not need to be the most recent treatment for CML NOTE: **Imatinib mesylate dose ≤ 600 mg/day - Able to tolerate chronic administration of imatinib mesylate at the highest dose received during prior treatment - No imatinib mesylate-related non-hematologic toxicity ≥ grade 3 - No grade 4 imatinib mesylate-related hematologic toxicity lasting more than 7 days - No imatinib mesylate-related toxicity that led to discontinuation or disruption of dosing for > 4 weeks - No previously identified BCR-ABL mutation of 1 of the following types: - L248V - G250E - Q252H/R - Y253H/F - E255K/V - T315I/D - F317L - H369P/R - No prior diagnosis of accelerated phase or blast crisis CML - Patients who previously met the criteria for accelerated phase or blast crisis CML who achieved CHR during treatment with imatinib mesylate and then subsequently progressed to chronic phase CML are not eligible - Ineligible for or unwilling to undergo hematopoietic stem cell transplantation PATIENT CHARACTERISTICS: Age - 18 and over Performance status - ECOG 0-1 Life expectancy - At least 3 months Hematopoietic - See Disease Characteristics - No history of a significant bleeding disorder unrelated to CML, including any of the following: - Congenital bleeding disorder (e.g., von Willebrand's disease) - Acquired bleeding disorder diagnosed within the past year (e.g. --- L248V --- --- G250E --- --- Q252H --- --- Y253H --- --- E255K --- --- T315I --- --- F317L ---

acquired anti-factor VIII antibodies) Hepatic - Bilirubin ≤ 2.0 times upper limit of normal (ULN) - ALT and AST ≤ 2.5 times ULN Renal - Creatinine ≤ 1.5 times ULN - Total serum or ionized calcium normal (supplementation allowed) Cardiovascular - Heart rate ≥ 50 beats/minute by EKG - No myocardial infarction within the past 6 months - No uncontrolled angina within the past 3 months - No congestive heart failure within the past 3 months - No diagnosed or suspected congenital long QT syndrome - No history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de Pointes) - No prolonged QTc interval (i.e., > 450 msec) by EKG using Bazett's correction - High Bazett's correction (i.e., > 450 msec) allowed provided Fridericia correction is ≤ 450 msec - No history of second or third degree heart block - Pacemaker allowed - No uncontrolled hypertension - No other uncontrolled or significant cardiovascular disease Other - Not pregnant - No nursing during and for ≥ 3 months after study participation - Negative pregnancy test - Fertile patients must use effective contraception for ≥ 1 month before, during, and for ≥ 3 months after study participation - Magnesium and potassium normal (supplementation allowed) - No serious uncontrolled medical disorder or active infection that would preclude study participation - No dementia or altered mental status that would preclude giving informed consent - No significant bleeding from the gastrointestinal tract within the past 6 months - No evidence of organ dysfunction or any clinically significant deviation from normal on physical examination, vital signs, EKG, or clinical laboratory determinations unrelated to CML that would preclude study participation - No prisoners or patients who are involuntarily incarcerated for treatment of either a psychiatric or physical (e.g., infectious disease) illness PRIOR CONCURRENT THERAPY: Biologic therapy - More than 14 days since prior interferon Chemotherapy - More than 14 days since prior cytarabine - Prior or concurrent hydroxyurea for elevated WBC (i.e., WBC > 50,000/mm^3) allowed Endocrine therapy - Not specified Radiotherapy - Not specified Surgery - Not specified Other - More than 7 days since prior imatinib mesylate - At least 7 days since prior and no concurrent low-dose aspirin (≤ 325 mg/day) - At least 14 days since prior and no concurrent high-dose aspirin (> 325 mg/day) - More than 14 days since prior targeted small molecule anticancer agents - More than 28 days since prior investigational or antineoplastic agents except hydroxyurea or anagrelide - At least 5 days or 5 half-lives (whichever is greater) since prior and no concurrent drugs that carry a risk of causing torsades de Pointes, including any of the following: - Quinidine - Procainamide - Disopyramide - Amiodarone - Sotalol - Ibutilide - Dofetilide - Erythromycin - Clarithromycin - Chlorpromazine - Haloperidol - Mesoridazine - Thioridazine - Pimozide - Ziprasidone - Cisapride - Bepridil - Droperidol - Methadone - Arsenic trioxide - Chloroquine - Domperidone - Halofantrine - Levomethadyl - Pentamidine - Sparfloxacin - Lidoflazine - At least 5 days or 5 half-lives (whichever is greater) since prior and no concurrent medication that directly inhibits platelet function (except anagrelide for thrombocytosis due to CML), including any of the following: - Dipyridamole - Epoprostenol - Epitifibatide - Clopidogrel - Cilostazol - Abciximab - Ticlopidine - At least 5 days or 5 half-lives (whichever is greater) since prior and no concurrent anticoagulants (e.g., warfarin, heparin, or low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin]) - Concurrent prophylactic low-dose warfarin for prevention of catheter thrombosis and heparin-flush for IV lines allowed - No prior BMS-354825 - No concurrent CYP3A4 inhibitors or inducers, including any of the following: - Ketoconazole - Ritonavir - Rifampin - Efavirenz - No other concurrent therapy for CML DISEASE CHARACTERISTICS: - Diagnosis of chronic phase chronic myelogenous leukemia (CML), meeting all of the following criteria: - Less than 15% blasts in peripheral blood and bone marrow - Less than 20% basophils in peripheral blood - Less than 30% blasts and promyelocytes in peripheral blood and bone marrow - Platelet count ≥ 100,000/mm^3 (unless thrombocytopenia is due to recent therapy) - No extramedullary involvement (other than liver or spleen) - Philadelphia chromosome (Ph)-positive disease by cytogenetic analysis - Must have developed resistant disease during prior treatment with imatinib mesylate* at a dose of 400-600 mg/day**, as defined by 1 of the following: - Loss of major cytogenetic response (MCyR) - Achieved a confirmed MCyR and subsequently no longer meets the MCyR criteria - Documented increase in Ph-positive metaphases by 30% on 2 cytogenetic analyses performed ≥ 4 weeks apart during treatment with imatinib mesylate - Loss of complete hematologic response (CHR) - Achieved a confirmed CHR and subsequently no longer meets the CHR criteria on all asessments over a consecutive 2-week period during treatment with imatinib mesylate - Continuously increasing WBC count on ≥ 2 consecutive evaluations ≥ 2 weeks apart with the final assessment showing a doubling of WBC from the nadir to ≥ 20,000/mm^3 OR an absolute increase in WBC by > 50,000/mm^3 above the lowest count after starting imatinib mesylate - No CHR after 3 months of treatment with imatinib mesylate at a dose of 400-600 mg/day - No cytogenetic response after 6 months of treatment with imatinib mesylate at a dose of 400-600 mg/day - No MCyR after 12 months of treatment with imatinib mesylate at a dose of 400-600 mg/day NOTE: *Imatinib mesylate does not need to be the most recent treatment for CML NOTE: **Imatinib mesylate dose ≤ 600 mg/day - Able to tolerate chronic administration of imatinib mesylate at the highest dose received during prior treatment - No imatinib mesylate-related non-hematologic toxicity ≥ grade 3 - No grade 4 imatinib mesylate-related hematologic toxicity lasting more than 7 days - No imatinib mesylate-related toxicity that led to discontinuation or disruption of dosing for > 4 weeks - No previously identified BCR-ABL mutation of 1 of the following types: - L248V - G250E - Q252H/R - Y253H/F - E255K/V - T315I/D - F317L - H369P/R - No prior diagnosis of accelerated phase or blast crisis CML - Patients who previously met the criteria for accelerated phase or blast crisis CML who achieved CHR during treatment with imatinib mesylate and then subsequently progressed to chronic phase CML are not eligible - Ineligible for or unwilling to undergo hematopoietic stem cell transplantation PATIENT CHARACTERISTICS: Age - 18 and over Performance status - ECOG 0-1 Life expectancy - At least 3 months Hematopoietic - See Disease Characteristics - No history of a significant bleeding disorder unrelated to CML, including any of the following: - Congenital bleeding disorder (e.g., von Willebrand's disease) - Acquired bleeding disorder diagnosed within the past year (e.g. --- L248V --- --- G250E --- --- Q252H --- --- Y253H --- --- E255K --- --- T315I --- --- F317L ---

Primary Outcomes

Measure: Major cytogenic response (MCyR) rate at 12 weeks

Secondary Outcomes

Measure: MCyR at any time

Measure: Duration of MCyR

Measure: Time to MCyR

Measure: Complete hematologic response rate

2 A Phase II Study of Dasatinib in Patients With Imatinib Resistant or Intolerant Chronic Myeloid Leukemia

The purpose of this study is to evaluate the efficacy and the safety of dasatinib in subject with chronic phase chronic myeloid leukemia(CML) who are either resistant to or intolerant of imatinib mesylate.

NCT00866736 Chronic Myeloid Leukemia Drug: dasatinib
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

- Prior therapy with dasatinib - Subjects with T315I and/or F317L BCR-ABL point mutations Inclusion Criteria: - Signed Written Informed Consent - Subjects with chronic phase chronic myeloid leukemia (CML) - Subjects resistant/intolerant to imatinib - Subjects presenting: 1. ECOG performance status (PS) score 0-2 2. Adequate hepatic function 3. Adequate renal function 4. Adequate lung function Exclusion Criteria: - Concurrent malignancy other than CML - Women who are pregnant or breastfeeding - Concurrent pleural effusion - Uncontrolled or significant cardiovascular disease - A serious uncontrolled medical disorder that would impair the ability of the subjects to receive protocol therapy. --- T315I --- --- F317L ---

- Prior therapy with dasatinib - Subjects with T315I and/or F317L BCR-ABL point mutations Chronic Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive null --- T315I --- --- F317L ---

Primary Outcomes

Measure: rate of Major Molecular Responses (MMR) in chronic phase chronic myeloid leukemia subjects

Time: at 12 months

Secondary Outcomes

Measure: safety after treatment with dasatinib

Time: 2 year

Measure: rate of Complete Cytogenetic Response(CCyR)

Time: 2 year

Measure: rate of Complete Hematologic Response (CHR)

Time: 2 year

Measure: efficacy on patients with BCR-ABL point mutations

Time: 2 year

Measure: progression free survival

Time: 2 year

3 A Study of Complete Molecular Response for Chronic Myeloid Leukemia in Chronic Phase Patients, Treated With Dasatinib

The purpose of this study is to evaluate complete molecular response of Dasatinib in patients for Philadelphia chromosome-positive chronic myeloid leukemia

NCT01342679 Chronic Myeloid Leukemia Drug: dasatinib
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

Inclusion Criteria: - Chronic Myeloid Leukemia in the Chronic Phase - 20 years old over - ECOG performance status (PS) score 0-2 - Patients for major molecular response (MMR) with no CMR - Adequate organ function (hepatic, renal and lung) - Signed written informed consent Exclusion Criteria: - A case with the double cancer of the activity - Women who are pregnant or breastfeeding - The case of Pleural effusion clearly - Patients with complications or a history of severe or uncontrolled cardiovascular failure following - have a Myocardial infarction within 6 months - have an Angina within 3 months - have a Congestive heart failure within 3 months - have a suspected congenital QT syndrome - have a QTc interval of more than 450msec at baseline - A serious uncontrolled medical disorder that would impair the ability of the subjects to receive protocol therapy - Prior treatment with dasatinib - Subjects with T315I, F317L and V299L BCR-ABL point mutations Inclusion Criteria: - Chronic Myeloid Leukemia in the Chronic Phase - 20 years old over - ECOG performance status (PS) score 0-2 - Patients for major molecular response (MMR) with no CMR - Adequate organ function (hepatic, renal and lung) - Signed written informed consent Exclusion Criteria: - A case with the double cancer of the activity - Women who are pregnant or breastfeeding - The case of Pleural effusion clearly - Patients with complications or a history of severe or uncontrolled cardiovascular failure following - have a Myocardial infarction within 6 months - have an Angina within 3 months - have a Congestive heart failure within 3 months - have a suspected congenital QT syndrome - have a QTc interval of more than 450msec at baseline - A serious uncontrolled medical disorder that would impair the ability of the subjects to receive protocol therapy - Prior treatment with dasatinib - Subjects with T315I, F317L and V299L BCR-ABL point mutations Chronic Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive null --- T315I --- --- F317L ---

Inclusion Criteria: - Chronic Myeloid Leukemia in the Chronic Phase - 20 years old over - ECOG performance status (PS) score 0-2 - Patients for major molecular response (MMR) with no CMR - Adequate organ function (hepatic, renal and lung) - Signed written informed consent Exclusion Criteria: - A case with the double cancer of the activity - Women who are pregnant or breastfeeding - The case of Pleural effusion clearly - Patients with complications or a history of severe or uncontrolled cardiovascular failure following - have a Myocardial infarction within 6 months - have an Angina within 3 months - have a Congestive heart failure within 3 months - have a suspected congenital QT syndrome - have a QTc interval of more than 450msec at baseline - A serious uncontrolled medical disorder that would impair the ability of the subjects to receive protocol therapy - Prior treatment with dasatinib - Subjects with T315I, F317L and V299L BCR-ABL point mutations Inclusion Criteria: - Chronic Myeloid Leukemia in the Chronic Phase - 20 years old over - ECOG performance status (PS) score 0-2 - Patients for major molecular response (MMR) with no CMR - Adequate organ function (hepatic, renal and lung) - Signed written informed consent Exclusion Criteria: - A case with the double cancer of the activity - Women who are pregnant or breastfeeding - The case of Pleural effusion clearly - Patients with complications or a history of severe or uncontrolled cardiovascular failure following - have a Myocardial infarction within 6 months - have an Angina within 3 months - have a Congestive heart failure within 3 months - have a suspected congenital QT syndrome - have a QTc interval of more than 450msec at baseline - A serious uncontrolled medical disorder that would impair the ability of the subjects to receive protocol therapy - Prior treatment with dasatinib - Subjects with T315I, F317L and V299L BCR-ABL point mutations Chronic Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive null --- T315I --- --- F317L --- --- V299L --- --- T315I --- --- F317L ---

Primary Outcomes

Measure: Rate of complete molecular response (CMR) after treatment with dasatinib

Time: at 12 months

Secondary Outcomes

Measure: Dasatinib of dose intensity

Time: at 12 months

Measure: Expansions rate of large granular lymphocyte

Time: at 12 months

Measure: Progression free survival

Time: at 12 months

Measure: Number of Participants with Adverse Events

Time: at 12 months

4 Dynamics of ABL Mutations in Imatinib Failed Ph Positive or Bcr-Abl Positive CML CP or AP Patients Who Treated With Nilotinib as Second-line TKI Therapy (AMICAN-Prospective)in Asia

The purposes of this study are to investigate expression and frequency of ABL point mutations, a major cause of resistance in imatinib failed CML Asian patients and to find causes of Asian-specific resistance to cancer-targeting therapies through a prospective investigation of dynamics of point mutations and expression of new point mutations during nilotinib treatment.

NCT01562847 Chronic Myeloid Leukemia Drug: Nilotinib
MeSH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia

With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L ---

Primary Outcomes

Measure: To confirm the patterns of resistance including point mutations which are newly expressed during the nilotinib treatment

Time: 5 years

Secondary Outcomes

Measure: To analyze and evaluate the overall survival and disease free survival in the nilotinib treatment according to progression of the disease and types of point mutations

Time: 5 years

5 An Open Label, Randomized (2:1) Phase IIb Study of Dasatinib Versus Imatinib in Patients With Chronic Phase Chronic Myeloid Leukemia Who Have Not Achieved an Optimal Response to 3 Months of Therapy With 400 mg Imatinib

The purpose of this study is to test the hypothesis that patients with CML who have not achieved optimal response after 3 months of treatment with imatinib will have a better response by switching to dasatinib compared to staying on their original imatinib regimen.

NCT01593254 Chronic Phase Chronic Myeloid Leukemia Drug: Imatinib Drug: Dasatinib
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study - Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement - Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening) - A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. --- T315I --- --- F317L ---

Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study - Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement - Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening) - A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy Chronic Phase Chronic Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase null --- T315I --- --- F317L ---

Primary Outcomes

Description: Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR; N/A = not applicable. 95% CI is Clopper-Pearson(Exact) two-sided 95% confidence intervals. P-value is based on Cochran-Mantel-Haenszel (CMH) test stratified by Sokal score(high, intermediate, low, and unknown) and time between 3 month molecular analysis and randomization (<=4 weeks vs >4 weeks). Month 12 is calculated fro

Measure: Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment

Time: At 12 months after Day 1 initiation of 1st line treatment with imatinib or imatinib at any dose, after less than optimal response to first-line imatinib.

Secondary Outcomes

Description: Time to MMR is how fast patients achieve optimal response. It is the time between randomization date and first date that MMR criteria are satisfied.

Measure: Median Time to Major Molecular Response (MMR)

Time: Up to 10 years

Description: Time to MR^4.5 is how fast patients achieve a deeper response. It is the time between randomization date and first date that MR^4.5 criteria are satisfied.

Measure: Time to Molecular Response (MR)^4.5

Time: Up to 10 years

Description: PFS is how long patients are likely to live without progression of their disease. It is the time from randomization date to progression date or death date, whichever occurs first.

Measure: Progression Free Survival (PFS)

Time: Up to 10 years

Description: OS is how long patients are likely to remain alive. It is the time from randomization date to death date.

Measure: Overall Survival (OS)

Time: Up to 10 years

6 Discontinuation of Dasatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Who Have Maintained Complete Molecular Remission for Two Years; Dasatinib Stop Trial

The purpose of this study is to assess whether dasatinib can be discontinued without occurrence of molecular relapse in patients with chronic myeloid leukemia in chronic phase in complete molecular remission (CMR) while on dasatinib.

NCT01627132 Chronic Myeloid Leukemia Drug: Dasatinib
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

- Patients with mutation of T315I, F317L, V299L. --- T315I --- --- F317L ---

Primary Outcomes

Measure: The overall probability of maintenance of complete molecular remission at 12 months after stopping dasatinib.

Time: at 12 months

Secondary Outcomes

Measure: Rate of complete molecular remission that will be sustained after dasatinib rechallenge.

Time: at 12 months

7 Phase I Trial Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older.

The purpose of this study is to test the safety of a new combination of three oral drugs in Ph+ ALL. These drugs are dexamethasone, dasatinib, and ruxolitinib. All three drugs have been studied before in humans. This is a phase I study in which ruxolitinib dose will start low for the first patient together with dexamethasone plus dasatinib. If this dose does not cause a bad side effect, the ruxolitinib dose will slowly be made higher as new patients take part in the study. This will help the investigators find the right dose of ruxolitinib to give together with dexamethasone and dasatinib that will be used in future studies

NCT02494882 Acute Lymphoblastic Leukemia Drug: Ruxolitinib Drug: Dasatinib Drug: Dexamethasone
MeSH: Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Philadelphia Chromosome
HPO: Leukemia Lymphoid leukemia

L248R, L248V, Q252H, E255K, V299L, T315A, T315I, F317C, F317L, F317S, F317V) - Relapsed or refractory Ph-like ALL without prior exposure to dasatibin and with mutations or rearrangements of genes conferring sensitivity to dasatibin (ABL, CSF1R, PDGFRB) or ruxolitinib (CRLF2, JAK3, EPOR, TSLP) - Newly diagnosed or relapsed CML in lymphoid blast crisis - Confirmation of Philadelphia chromosome positivity by cytogenetics (karyotype/FISH) and/or molecular tests (BCR-ABL1 transcripts) - Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself - ECOG performance status ≤ 2 - Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and for at least 4 months following treatment on study Exclusion Criteria: - Ph-negative ALL - Patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis - Mature B-cell (Burkitt's) ALL - Serum creatinine > 1.5x ULN and calculated creatinine clearance, based on a 24-hour urine collection, < 30 mL/min--unless related to ALL/tumor lysis syndrome and able to be corrected - Direct Bilirubin > 2x ULN; AST/ALT > 10x ULN, unless related to ALL liver infiltration. --- L248R --- --- L248V --- --- Q252H --- --- E255K --- --- V299L --- --- T315A --- --- T315I --- --- F317C --- --- F317L ---

Primary Outcomes

Description: is to be evaluated by using a combination of criteria. Molecular remissions will be defined by standard criteria for BCR-ABL1 and IGH qRT-PCR. Flow cytometric assessment of MRD will be defined by standard flow cytometry criteria

Measure: Clinical response

Time: 2 years

Secondary Outcomes

Description: Molecular remission status will be defined by undetectable BCR-ABL1 transcripts and/or IGH clonal gene rearrangement in bone marrow aspirate (BMA) examination as determined by qRT-PCR in CLIA laboratory.

Measure: Complete Molecular Remission (CMR) rate

Time: 2 years


HPO Nodes


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
Chronic myelogenous leukemia
Genes 9
KIT MPL ASXL1 TET2 ABL1 JAK2 THPO BCR SRSF2
Myeloid leukemia
Genes 20
KIT SETBP1 NF1 ARHGAP26 CBL TET2 KRAS PTPN11 F13A1 SAMD9L SAMD9L GATA2 CBL ASXL1 DNMT3A F13B NRAS SRSF2 TERC TERT
Lymphoid leukemia