Dasatinib in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00345826
First received: June 28, 2006
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

RATIONALE: Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects of dasatinib in treating patients with chronic myelogenous leukemia or acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
Drug: dasatinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Subjects Who Experienced Clinical Benefit on Protocol CA 180-002

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Long term safety and tolerability [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: November 2005
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib Drug: dasatinib

Detailed Description:

OBJECTIVES:

Primary

  • Determine the long-term safety and tolerability of dasatinib in patients with Philadelphia chromosome-positive chronic myelogenous leukemia or acute lymphoblastic leukemia resistant or intolerant to imatinib mesylate.

Secondary

  • Describe any hematologic or cytogenetic response in patients treated with this drug.
  • Determine the duration of hematologic and cytogenetic response in patients using this drug during trial UCLA-0303035.
  • Determine the progression-free survival and overall survival of patients treated with this drug.

OUTLINE: This is an open-label, roll-over study of protocol UCLA-0303035.

Patients receive oral dasatinib once or twice daily for 5, 6, or 7 days. Treatment repeats every 7 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following hematologic malignancies:

    • Chronic phase chronic myelogenous leukemia (CML)

      • In complete hematologic response after treatment on protocol UCLA-0303035, as indicated by the following criteria:

        • WBC ≤ upper limit of normal (ULN)
        • Platelet count < 450,000/mm^3
        • No blasts or promyelocytes in peripheral blood
        • Less than 5% myelocytes plus metamyelocytes in peripheral blood
        • Peripheral blood basophils ≤ ULN
        • No extramedullary involvement (including no hepatomegaly or splenomegaly)
        • Response lasting ≥ 4 weeks after first documentation
    • Accelerated or blastic phase CML or acute lymphoblastic leukemia

      • In major hematologic response* after treatment on protocol UCLA-0303035, defined as 1 of the following:

        • In complete hematologic response*, as indicated by the following criteria:

          • WBC ≤ ULN
          • Absolute neutrophil count ≥ 1,000/mm^3
          • Platelet count ≥ 100,000/mm^3
          • No blasts or promyelocytes in peripheral blood
          • Bone marrow blasts ≤ 5%
          • Less than 5% myelocytes plus metamyelocytes in peripheral blood
          • Peripheral blood basophils ≤ ULN
          • No extramedullary involvement (including no hepatomegaly or splenomegaly)
        • No evidence of leukemia, as indicated by the following criteria:

          • WBC ≤ ULN
          • No blasts or promyelocytes in the peripheral blood
          • Bone marrow blasts ≤ 5%
          • Less than 5% myelocytes plus metamyelocytes in peripheral blood
          • Peripheral blood basophils ≤ ULN
          • No extramedullary involvement (including no hepatomegaly or splenomegaly)
          • Absolute neutrophil count ≥ 500/mm^3 and < 1,000/mm^3 AND platelet count ≥ 20,000/mm^3 and < 100,000/mm^3
      • In minor hematologic response* after treatment on protocol UCLA-0303035, as indicated by the following criteria:

        • Less than 15% in bone marrow and < 15% in peripheral blood
        • Less than 30% blasts plus promyelocytes in bone marrow and < 30% blasts plus promyelocytes in peripheral blood
        • Less than 20% basophils in peripheral blood
        • No extramedullary disease other than spleen and liver NOTE: *Response confirmed after ≥ 4 weeks allowed provided there is no concurrent anagrelide or hydroxyurea during this time
  • Philadelphia chromosome-positive (Ph+) disease
  • Resistant or intolerant to prior imatinib mesylate
  • Received and benefitted from ≥ 3 months of prior therapy with dasatinib on protocol UCLA-0303035

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment
  • No serious uncontrolled medical disorder
  • No active infection that would preclude study participation
  • No uncontrolled angina within the past 3 months
  • No diagnosed or suspected congenital long QT syndrome
  • No history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
  • QTc ≤ 450 msec on electrocardiogram
  • No uncontrolled hypertension
  • No dementia or altered mental status the would prohibit the understanding or rendering of informed consent
  • No history of the following significant bleeding disorders unrelated to CML:

    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
    • Diagnosed acquired bleeding disorder in the past year (e.g., acquired antifactor VIII antibodies)
  • Not involuntarily incarcerated for either psychiatric or physical (e.g., infectious disease) illness
  • No patients who are imprisoned
  • No clinical adverse event, laboratory abnormality, or intercurrent illness that may preclude study treatment, in the opinion of the investigator
  • Bilirubin < 1.5 mg/dL
  • ALT and AST < 2 times upper limit of normal (ULN)
  • Creatinine < 1.5 times ULN

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No concurrent use of the following drugs that may confer risk of torsades de pointes:

    • Quinidine
    • Procainamide
    • Disopyramide
    • Amiodarone
    • Sotalol
    • Ibutilide
    • Dofetilide
    • Erythromycin
    • Clarithromycin
    • Chlorpromazine
    • Haloperidol
    • Mesoridazine
    • Thioridazine
    • Pimozide
    • Cisapride
    • Bepridil
    • Droperidol
    • Methadone
    • Arsenic
    • Chloroquine
    • Domperidone
    • Halofantrine
    • Levomethadyl
    • Pentamidine
    • Sparfloxacin
    • Lidoflazine
  • No other concurrent treatment for CML except for hydroxyurea for a 2-week duration
  • No concurrent medications that inhibit platelet function (e.g., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, or any nonsteroidal anti-inflammatory drug)* except for hydroxyurea or anagrelide
  • No concurrent anticoagulants (e.g., warfarin or heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin]) except as prophylaxis for catheter thrombosis and/or heparin flushes for IV lines* NOTE: *Allowed if received previously on UCLA-0303035
  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: NCT00345826

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Charles Sawyers, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00345826     History of Changes
Other Study ID Numbers: CDR0000480396, UCLA-0509010-01, BMS-CA180039
Study First Received: June 28, 2006
Last Updated: January 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Jonsson Comprehensive Cancer Center:
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
recurrent adult acute lymphoblastic leukemia
chronic myelogenous leukemia, BCR-ABL1 positive

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
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 July 20, 2014