RATIONALE: PHA-739358 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well PHA-739358 works in treating patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.
Name: danusertib
Type: Drug
Name: laboratory biomarker analysis
Type: Other
Name: pharmacological study
Type: OtherThere is one SNP
DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive OBJECTIVES: - Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting ≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy. --- T315I ---
DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial DISEASE CHARACTERISTICS: - Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy - Chronic, accelerated, or blastic phase disease - May have T315I mutation in BCR-ABL kinase - Relapsed after prior imatinib mesylate or c-ABL therapy - No CNS leukemia PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) - Transaminases ≤ 2.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - Creatinine ≤ 1.5 times ULN - No known history of HIV infection - No active uncontrolled infection - No grade 3 or 4 bleeding - LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography - No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment - No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months - No major thromboembolic event within the past 6 months, including any of the following: - Myocardial infarction - Stroke - Transient ischemic attack - Pulmonary embolism - Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: - Recovered from all acute toxic effects (excluding alopecia) of prior therapy - More than 2 weeks since prior chemoimmunotherapy - Hydroxyurea must be discontinued 1 day prior to study therapy - More than 4 weeks since prior major surgery - No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy - No other concurrent investigational drugs - No concurrent participation in another treatment clinical trial Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive OBJECTIVES: - Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting ≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy. --- T315I --- --- T315I ---
- Explore response depending on status of T315I mutation in BCR-ABL kinase. --- T315I ---