Dasatinib and Venetoclax in Treating Patients With Philadelphia Chromosome Positive or BCR-ABL1 Positive Early Chronic Phase Chronic Myelogenous Leukemia
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ClinicalTrials.gov Identifier: NCT02689440 |
Recruitment Status :
Recruiting
First Posted : February 24, 2016
Last Update Posted : January 25, 2022
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Condition or disease | Intervention/treatment | Phase |
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Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia | Drug: Dasatinib Other: Laboratory Biomarker Analysis Drug: Venetoclax | Phase 2 |
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).
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 140 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib and Venetoclax: A Phase II Study |
Actual Study Start Date : | February 19, 2016 |
Estimated Primary Completion Date : | December 31, 2040 |
Estimated Study Completion Date : | December 31, 2040 |

Arm | Intervention/treatment |
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Experimental: Treatment (dasatinib, venetoclax)
Patients receive dasatinib PO 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).
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Drug: Dasatinib
Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Venetoclax Given PO
Other Names:
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- Major molecular response (MMR) defined as BCR-ABL transcripts (IS) =< 0.1% [ Time Frame: Up to 12 months ]MMR estimates will be presented with 95% credible intervals. MMR and patient and clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
- Complete cytogenetic response (CCR) defined as 0% Ph-positive metaphases, or fluorescence in situ hybridization =< 2%, or BCR-ABL transcripts (IS) =< 1% [ Time Frame: At 6 months ]CCR estimates will be presented with 95% credible intervals.
- Incidence of toxicities, defined as grade 3 or higher pleural effusion [ Time Frame: Up to 3 years ]Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range (i.e., duration of hematologic, cytogenetic and molecular response to the drug).
- Time to progression [ Time Frame: Up to 3 years ]Estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups.
- Overall survival [ Time Frame: Up to 3 years ]Estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of Philadelphia chromosome (Ph)-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis is 12 months); except for hydroxyurea and/or 1 to 2 doses of cytarabine patients, patients must have received no or minimal prior therapy, defined as < 1 month (30 days) of prior Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI)
- Patients with clonal evolution and no other criteria for accelerated phase will be eligible for this study
- Eastern Cooperative Oncology Group (ECOG) performance of 0-2
- Total bilirubin < 1.5 x upper limit normal (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
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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 corrected QT (QTc) interval on pre-entry electrocardiogram (> 460 msec)
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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)
- 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)
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Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment; Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface [HBs] antigen negative-, anti-HBs antibody positive and anti-hepatitis B core [HBc] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
- 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
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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:
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Early chronic phase:
- Time from diagnosis to therapy 12 months
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Late chronic phase:
- Time from diagnosis to therapy > 12 months
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Blastic phase:
- Presence of 30% blasts or more in the peripheral blood or bone marrow
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Accelerated phase CML:
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Presence of any of the following features:
- Peripheral or marrow blasts 15% or more
- Peripheral or marrow basophils 20% or more
- Thrombocytopenia < 100 x 10^9/L unrelated to therapy
- Documented extramedullary blastic disease outside liver or spleen
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689440
Contact: Hagop Kantarjian | 713-792-7026 | hkantarjian@mdanderson.org |
United States, Texas | |
M D Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Hagop M. Kantarjian 713-792-7026 hkantarjian@mdanderson.org | |
Principal Investigator: Hagop M. Kantarjian |
Principal Investigator: | Hagop M Kantarjian | M.D. Anderson Cancer Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT02689440 |
Other Study ID Numbers: |
2015-1040 NCI-2016-00362 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2015-1040 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
First Posted: | February 24, 2016 Key Record Dates |
Last Update Posted: | January 25, 2022 |
Last Verified: | January 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Philadelphia Chromosome Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
Translocation, Genetic Chromosome Aberrations Pathologic Processes Dasatinib Venetoclax Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |