Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) with Dasatinib
The goal of this clinical research study is to learn if giving half of the recommended FDA approved dose of dasatinib can help to control CML as effectively as the full dose of dasatinib. Researchers also want to learn if combining venetoclax with dasatinib after 3 months of dasatinib alone is helpful in controlling CML compared to dasatinib alone. The safety of the combination will also be studied.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: Dasatinib
Treatment Location: Only at MDACC
Primary: To estimate the proportion of patients with previously-untreated chronic phase CML who achieve major molecular response by 12 months of treatment with dasatinib 50mg 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: To estimate the 12 months MR4.5 rate and the cumulative overall rate of MR4.5 (BCR-ABL transcripts (IS) < 0.01%). To estimate the proportion of patients with MR4.5 at 6-, 12-, 18-, 24-, and 36-months of therapy. To estimate the proportion of patients with sustained MR4.5 of 3 years and more. To estimate the treatment-free remission rate, time to progression, and overall survival. To assess the safety of this combination.
IRB Review and Approval Date: 02/19/2016
Recruitment Status: Open
Projected Accrual: N/A
1) Diagnosis of Ph-positive or BCR-ABL positive CML in early chronic
phase CML (i.e., time from diagnosis is12 months). Except
forhydroxyruea, patients must have received no or minimal prior therapy,
defined as <1 month (30 days) of prior FDA approved TKI.
2) Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has been historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study.
3) ECOG performance of 0-2.
4) Adequate end organ function, defined as the following: total bilirubin <1.5x ULN, SGPT <2.5x ULN, creatinine <1.5x ULN.
5) 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.
1) NYHA cardiac class 3-4 heart disease
2) Cardiac Symptoms: Patients meeting the following criteria are not eligible unless cleared by Cardiology: 1. Uncontrolled angina within 3 months. 2.Diagnosed or suspected congenital long QT syndrome. 3. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). 4. Prolonged QTc interval on pre-entry electrocardiogram (> 460 msec). 5.History of significant bleeding disorder unrelated to cancer, including: Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
3) Patients with active, uncontrolled psychiatric disorders include: psychosis, major depression, and bipolar disorders.
4) 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 investigational product and must not be enrolled in the study.
5) 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: a.Early chronic phase: time from diagnosis to therapy ? 12 months. Late chronic phase: time from diagnosis to therapy > 12 months. b. Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow. c.Accelerated phase CML: presence of any of the following features: • Peripheral or marrow blasts 15% or more • Peripheral or marrow basophils 20% or more • Thrombocytopenia < 100 x 109/L unrelated to therapy • Documented extramedullary blastic disease outside liver or spleen
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
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