Study of Dasatinib in Patients With Chronic Myelogenous Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00254423
First received: November 14, 2005
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Chronic Myelogenous Leukemia
Drug: Dasatinib (BMS-354825)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 up to 12 months ] [ Designated as safety issue: No ]
    MMR measured every 3 months, a total of 4 assessments within one year of therapy. Molecular response is defined as: a) Major (MMR): BCR-ABL/ABL ratio < 0.05%; or b) Complete: Undetectable BCR-ABL, confirmed by nested polymerase chain reaction (PCR).


Estimated Enrollment: 150
Study Start Date: November 2005
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib Daily (Arm A)
Dasatinib Daily Arm A: Starting dose 100 mg orally daily
Drug: Dasatinib (BMS-354825)

Arm A: Starting dose 100 mg orally daily

Arm B: Starting dose of 50 mg orally twice daily

Other Name: SPRYCEL ™
Experimental: Dasatinib Twice Daily (Arm B)
Dasatinib Twice Daily Arm B: Starting dose of 50 mg orally twice daily
Drug: Dasatinib (BMS-354825)

Arm A: Starting dose 100 mg orally daily

Arm B: Starting dose of 50 mg orally twice daily

Other Name: SPRYCEL ™

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.

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 as often as the doctor thinks it is needed. A bone marrow aspiration will also be taken to check the status of the disease every 3-4 months for the first year and then as often as the doctor thinks it is needed for as long as you are on the study.

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 recommended 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 8-10 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 MD 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-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 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 (Age >18 years to participate in optional symptom burden assessment)
  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.
  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:

  1. New York Heart Association (NYHA) cardiac class 3-4 heart disease
  2. 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:
  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: 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.
  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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00254423

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

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00254423     History of Changes
Other Study ID Numbers: 2005-0422, NCI-2012-01317
Study First Received: November 14, 2005
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 19, 2014