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Study of Dasatinib in Patients With Chronic Myelogenous Leukemia
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, August 2009
First Received: November 14, 2005   Last Updated: August 24, 2009   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
Bristol-Myers Squibb
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00254423
  Purpose

The goal of this clinical research study is to learn if BMS-354825 (dasatinib) can help to control chronic myelogenous leukemia (CML) in chronic phase. The safety of this drug will also be studied.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Drug: Dasatinib (BMS-354825)
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title: Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib (BMS-354825)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Time to first Molecular Response prior to 12 months (MMR) [ Time Frame: MMR measured every 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: November 2005
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Dasatinib Daily (Arm A): Experimental Drug: Dasatinib (BMS-354825)

Arm A: Starting dose 100 mg orally daily

Arm B: Starting dose of 50 mg orally twice daily

Dasatinib Twice Daily (Arm B): Experimental Drug: Dasatinib (BMS-354825)

Arm A: Starting dose 100 mg orally daily

Arm B: Starting dose of 50 mg orally twice daily


Detailed Description:

Dasatinib is an anticancer drug that is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing leukemia in certain cells.

Before you can start therapy on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. Blood (about 2 tablespoons) will be collected for routine tests. You will also have a bone marrow biopsy and aspiration. To collect a bone marrow biopsy and aspiration, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study and you agree, you will take dasatinib once every day while on study. Dasatinib should be taken by mouth with water.

Every 1-2 weeks during the first 4 weeks of the study, you will have around 2 tablespoons of blood drawn for routine blood tests. The blood tests will be repeated every 4-6 weeks until 1 year from when you started therapy and then every 3-4 months until 2 years, then every 4-6 months for as long as you are on the study. A bone marrow aspiration will also be taken every 3-4 months for the first year and then every 6-12 months until 3 years then every 2-3 years for as long as you are on the study to check on the status of the disease.

You will be given a medication diary to monitor any missed doses. You will also be asked to visit the doctor for a physical exam and to have vital signs measured periodically. These visits will be scheduled at least every 3-4 months for the first year, then every 6 to 12 months while you are on the study. The visits may be scheduled more often depending on the status of the disease.

Treatment may be continued for up to 3-5 years or as long as the doctor feels it is necessary to control the leukemia. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you. If you decide to stop participating in the study, you are encouraged to discuss your decision with your study doctor.

For Patients Already Enrolled:

If you have already been enrolled on this study and were assigned to receive dasatinib twice a day, you will be able to continue to receive the study drug on that schedule. However, if you experience side effects, the study doctor may choose to switch you to the once daily schedule if he feels that it may help to get rid of or decrease the risk of side effects.

This is an investigational study. Dasatinib is investigational and is approved by the FDA for clinical trials only. A total of 150 patients will take part in this study. All will be enrolled at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Ph-positive or Bcr-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 of prior IFN-alpha (with or without ara-C) and/or imatinib
  2. 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
  3. Age >/= 16 years
  4. 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
  6. 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:

  1. New York Heart Association (NYHA) cardiac class 3-4 heart disease
  2. Cardiac Symptoms: Patients meeting the following criteria are not eligible: 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:

  3. 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.
  4. Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders
  5. 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.
  6. Continued: In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. Women and men 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.
  7. Patients in late chronic phase (i.e., time from diagnosis to treatment >12 months), accelerated or blast phase are excluded.
  8. 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00254423

Contacts
Contact: Jorge Cortes, MD 713-794-5783

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Jorge Cortes, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Jorge Cortes, MD U.T.M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: The University of Texas M. D. Anderson Cancer Center ( Jorge Cortes M.D./Professor )
Study ID Numbers: 2005-0422
Study First Received: November 14, 2005
Last Updated: August 24, 2009
ClinicalTrials.gov Identifier: NCT00254423     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Chronic Myelogenous Leukemia
CML
Dasatinib
BMS-354825

Study placed in the following topic categories:
Leukemia
Hematologic Diseases
Dasatinib
Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Myelogenous Leukemia
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid
Bone Marrow Diseases
Protein Kinase Inhibitors

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Hematologic Diseases
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Protein Kinase Inhibitors
Pharmacologic Actions
Leukemia
Neoplasms
Dasatinib
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases

ClinicalTrials.gov processed this record on September 02, 2009