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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 : December 24, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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

Detailed 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).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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).
 Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Dasatinib Hydrate
  • Dasatinib Monohydrate
  • Sprycel

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Venetoclax
Given PO
Other Names:
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta
  • Venclyxto


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  • 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)

    • 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)

  • 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

  • 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:

        • Time from diagnosis to therapy > 12 months

    • Blastic phase:

      • Presence of 30% blasts or more in the peripheral blood or bone marrow

    • 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 10^9/L unrelated to therapy
        • Documented extramedullary blastic disease outside liver or spleen
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Hagop Kantarjian 713-792-7026 hkantarjian@mdanderson.org

Locations
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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         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Hagop M Kantarjian M.D. Anderson Cancer Center
More Information
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Additional Information:
MD Anderson Cancer Center Website  This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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: December 24, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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