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About
This phase II trial studies how well dasatinib and venetoclax work in treating patients with Philadelphia chromosome positive or BCR-ABL1 positive early chronic phase chronic myelogenous leukemia. Dasatinib and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Full description
PRIMARY OBJECTIVES:
I. To estimate the proportion of patients with previously-untreated chronic phase chronic myeloid leukemia (CML) who achieve major molecular response by 12 months of treatment with dasatinib 50 mg orally daily (first 70 patients) and of dasatinib 50 mg daily in combination with venetoclax 200 mg daily starting after 3 months of dasatinib therapy (after protocol amendment).
SECONDARY OBJECTIVES:
I. To estimate the 12 months molecular response (MR)4.5 rate and the cumulative overall rate of MR4.5 (BCR-ABL transcripts [IS] =< 0.01%).
II. To estimate the proportion of patients with MR4.5 at 6-, 12-, 18-, 24-, and 36-months of therapy.
III. To estimate the proportion of patients with sustained MR4.5 of 3 years and more.
IV. To estimate the treatment-free remission rate, time to progression, and overall survival.
V. To assess the safety of this combination.
OUTLINE:
Patients receive dasatinib orally (PO) once daily (QD) for 15 years in the absence of disease progression or unacceptable toxicity. After 3 months of dasatinib treatment, patients also receive venetoclax PO QD on days 1-14 of each month for 3 years in the absence of disease progression or unacceptable toxicity (patients enrolled prior to 4/1/2018 receive only dasatinib).
Enrollment
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Inclusion criteria
Diagnosis of Ph-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis ≤ 12 months). Except for hydroxyurea and/or 1 to 2 doses of cytarabine patients must have received no or minimal prior therapy, defined as <1 month (30 days) of prior FDA approved TKI.
Eastern Cooperative Oncology Group (ECOG) performance of 0-2
Total bilirubin < 1.5 x upper limit normal (ULN) (unless secondary to Gilbert's disease, in which case should be < 2.5x ULN)
Serum glutamate pyruvate transaminase (SGPT) < 3 x ULN
Creatinine < 1.5 x ULN
Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital
Exclusion criteria
New York Heart Association (NYHA) cardiac class 3-4 heart disease
Patients meeting the following criteria are not eligible unless cleared by cardiology:
Uncontrolled angina within 3 months
Diagnosed or suspected congenital long QT syndrome
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
Prolonged QTc interval on pre-entry electrocardiogram (> 460 msec)
History of significant bleeding disorder unrelated to cancer, including:
Patients with active, uncontrolled psychiatric disorders include: psychosis, major depression, and bipolar disorders
Subject is known to be positive for human immunodeficiency virus (HIV); (HIV testing is not required)
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
Women of pregnancy potential must practice an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women must continue birth control for the duration of the trial and at least 3 months after the last dose of study drug.
Pregnant or breast-feeding women are excluded. All WOCBP must have a negative pregnancy test prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive study drug and must not be enrolled in the study.
Patients in late chronic phase (i.e., time from diagnosis to treatment > 12 months), accelerated or blast phase are excluded; the definitions of CML phases are as follows:
Early chronic phase:
Time from diagnosis to therapy ≤12 months
Late chronic phase:
Blastic phase:
Accelerated phase CML:
Presence of any of the following features:
Primary purpose
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155 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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