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Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00254423
Recruitment Status : Active, not recruiting
First Posted : November 16, 2005
Last Update Posted : January 2, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This randomized phase II trial studies how well dasatinib works in treating patients with early chronic phase chronic myelogenous leukemia. Dasatinib may stop the growth of cancer 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 Other: Pharmacological Study Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To estimate the proportion of patients with previously-untreated chronic phase chronic myelogenous leukemia (CML) attaining major molecular response by 12 months of treatment with dasatinib.

SECONDARY OBJECTIVES:

I. To estimate the proportion of patients with Philadelphia chromosome (Ph)-positive early chronic phase CML achieving a complete cytogenetic response after dasatinib therapy.

II. To evaluate the durations of hematologic, cytogenetic and molecular response to dasatinib.

III. To define the time to progression and overall survival for patients with CML in early chronic phase treated with dasatinib.

IV. To evaluate the toxicity profile of dasatinib in patients with CML in early chronic phase.

V. To evaluate the probability of developing c-abl oncogene 1, non-receptor tyrosine kinase (ABL) mutations for patients with CML in early chronic phase treated with dasatinib.

VI. To analyze differences in response rates and in prognosis within different risk groups and patient characteristics.

VII. To assess correlation between trough concentration and pleural effusion. VIII. To assess the inhibition of platelet function and assess correlation between drug concentration and degree of platelet inhibition.

IX. To assess the effect of dasatinib therapy in bone metabolism as determined by changes in serum alkaline phosphatase (bone specific isoenzyme), and trabecular bone volume.

X. To evaluate symptom burden in patients with CML receiving dasatinib.

EXPLORATORY OBJECTIVE:

I. To investigate the plasma/serum levels of specific micro ribonucleic acids (miRNAs) in CML patients receiving dasatinib as initial therapy for CML in chronic phase (CP).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive dasatinib orally (PO) once daily (QD) for up to 15-18 years.

ARM B: Patients receive dasatinib PO twice daily (BID) for up to 15-18 years.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib (BMS-354825)
Actual Study Start Date : November 8, 2005
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2020


Arm Intervention/treatment
Experimental: Arm A (once daily dasatinib)
Patients receive dasatinib PO QD for up to 15-18 years.
Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Dasatinib Hydrate
  • Dasatinib Monohydrate
  • Sprycel

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Experimental: Arm B (twice daily dasatinib)
Patients receive dasatinib PO BID for up to 15-18 years.
Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Dasatinib Hydrate
  • Dasatinib Monohydrate
  • Sprycel

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Probability of major molecular response [ Time Frame: 12 months ]
  2. Toxicity rate [ Time Frame: 12 months ]

Other Outcome Measures:
  1. Symptom burden during dasatinib therapy (optional) [ Time Frame: Up to 12 months after last dose of study treatment ]
    Frequency tables will be used to summarize M. D. Anderson Symptom Inventory (MDASI)-CML and single-item quality of life (QOL) variables. Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.

  2. Symptom severity during dasatinib therapy [ Time Frame: Up to 12 months after last dose of study treatment ]
    Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.

  3. Therapy adherence during dasatinib therapy [ Time Frame: Up to 12 months after last dose of study treatment ]
    Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.

  4. Quality of life during dasatinib therapy [ Time Frame: Up to 12 months after last dose of study treatment ]
    Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL (quality of life).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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, patients must have received no or minimal prior therapy, defined as <1 month (30 days) of prior IFN-alpha (with or without ara-C) and/or an FDA approved TKI
  • Continued from above #1: 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
  • Age >/= 16 years (Age >18 years to participate in optional symptom burden assessment)
  • ECOG performance of 0-2

    5) Adequate end organ function, defined as the following: total bilirubin <1.5 x ULN, SGPT <2.5x ULN, creatinine <1.5x 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.

    7) Reliable telephone access to receive calls from an interactive voice response system (IVR) (only applicable to patients who will participate in optional symptom burden assessment)

Exclusion Criteria:

  • New York Heart Association (NYHA) cardiac class 3-4 heart disease
  • Cardiac Symptoms: 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 (> 450 msec) on both the Fridericia and Bazett's correction; Uncontrolled hypertension; History of significant bleeding disorder unrelated to cancer, including:
  • Cont: Diagnosed congenital bleeding disorders (von Willebrand's disease) Diagnosed acquired bleeding disorder w/in 1 year (acquired anti-factor VIII antibodies);Pts currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide amiodarone, sotalol, ibutilide, dofetilide erythromycins, clarithromycin chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
  • Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders
  • Women of pregnancy potential must practice 2 effective methods 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.
  • Continued: 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: 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 10^9/L unrelated to therapy, Documented extramedullary blastic disease outside liver or spleen

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): NCT00254423


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Lucia Masarova M.D. Anderson Cancer Center
Additional Information:
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: NCT00254423    
Other Study ID Numbers: 2005-0422
NCI-2012-01317 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-2010-00440
2005-0422 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: November 16, 2005    Key Record Dates
Last Update Posted: January 2, 2020
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
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action