- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00254423
Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia
Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib (BMS-354825)
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (once daily dasatinib)
Patients receive dasatinib PO QD for up to 15-18 years.
|
Correlative studies
Ancillary studies
Other Names:
Correlative studies
Ancillary studies
Given PO
Other Names:
|
Experimental: Arm B (twice daily dasatinib)
Patients receive dasatinib PO BID for up to 15-18 years.
|
Correlative studies
Ancillary studies
Other Names:
Correlative studies
Ancillary studies
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Probability of major molecular response
Time Frame: 12 months
|
12 months
|
Toxicity rate
Time Frame: 12 months
|
12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 12 months after last dose of study treatment
|
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.
|
Up to 12 months after last dose of study treatment
|
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.
|
Up to 12 months after last dose of study treatment
|
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).
|
Up to 12 months after last dose of study treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Lucia Masarova, MD, M.D. Anderson Cancer Center
Publications and helpful links
General Publications
- Jain P, Kantarjian H, Boddu PC, Nogueras-Gonzalez GM, Verstovsek S, Garcia-Manero G, Borthakur G, Sasaki K, Kadia TM, Sam P, Ahaneku H, O'Brien S, Estrov Z, Ravandi F, Jabbour E, Cortes JE. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv. 2019 Mar 26;3(6):851-861. doi: 10.1182/bloodadvances.2018025874.
- Issa GC, Kantarjian HM, Gonzalez GN, Borthakur G, Tang G, Wierda W, Sasaki K, Short NJ, Ravandi F, Kadia T, Patel K, Luthra R, Ferrajoli A, Garcia-Manero G, Rios MB, Dellasala S, Jabbour E, Cortes JE. Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment. Blood. 2017 Nov 9;130(19):2084-2091. doi: 10.1182/blood-2017-07-792143. Epub 2017 Aug 23.
- Jain P, Kantarjian H, Nazha A, O'Brien S, Jabbour E, Romo CG, Pierce S, Cardenas-Turanzas M, Verstovsek S, Borthakur G, Ravandi F, Quintas-Cardama A, Cortes J. Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood. 2013 Jun 13;121(24):4867-74. doi: 10.1182/blood-2013-03-490128. Epub 2013 Apr 25.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Chromosome Aberrations
- Translocation, Genetic
- Chronic Disease
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Philadelphia Chromosome
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Dasatinib
Other Study ID Numbers
- 2005-0422 (Other Identifier: M D Anderson Cancer Center)
- NCI-2012-01317 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- NCI-2010-00440
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedPrimary Myelofibrosis | Thrombocytopenia | Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingAcute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Accelerated Phase...United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingRecurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous LeukemiaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI); Astex Pharmaceuticals, Inc.RecruitingChronic Phase Chronic Myelogenous Leukemia | Philadelphia Chromosome Positive | BCR-ABL1 Positive Chronic Myelogenous Leukemia | BCR-ABL1 PositiveUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingChronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous LeukemiaUnited States
-
National Cancer Institute (NCI)CompletedChronic Phase Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)CompletedChronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)CompletedChildhood Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)TerminatedAccelerated Phase Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)CompletedChildhood Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized OsteosarcomaUnited States