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BMS-354825 in Treating Patients With Blastic Phase Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia That Did Not Respond to Previous Imatinib Mesylate
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00110097
  Purpose

RATIONALE: BMS-354825 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well BMS-354825 works in treating patients with blastic phase chronic myelogenous leukemia or acute lymphoblastic leukemia that did not respond to previous imatinib mesylate.


Condition Intervention Phase
Leukemia
Drug: dasatinib
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Imatinib Imatinib mesylate Dasatinib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of BMS-354825 in Subjects With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Resistant to or Intolerant of Imatinib Mesylate

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: January 2005
Detailed Description:

OBJECTIVES:

Primary

  • Determine the complete and overall hematologic response rate in patients with blastic phase chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL) with primary or acquired resistance to imatinib mesylate treated with BMS-354825.

Secondary

  • Determine the durability of hematologic response and time to complete and overall hematologic response in patients treated with this drug.
  • Determine the cytogenetic and molecular response in patients treated with this drug.
  • Determine the response rate in patients with no evidence of leukemia and in patients whose disease returns to chronic phase after treatment with this drug.
  • Determine the hematologic, cytogenetic, and molecular response in patients with imatinib mesylate-intolerant CML or ALL treated with this drug.
  • Determine the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene as predictors or surrogates of response in patients treated with this drug.
  • Determine the health-related quality of life of patients treated with this drug.
  • Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral BMS-354825 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 2 weeks for the first 3 courses, monthly thereafter during study treatment, and 30 days after completion of study treatment.

After completion of study treatment, patients are followed for at least 30 days.

PROJECTED ACCRUAL: A minimum of 60 patients (at least 30 with blastic phase chronic myelogenous leukemia and at least 30 with acute lymphoblastic leukemia) will be accrued for this study within 6 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Blastic phase chronic myelogenous leukemia (CML), meeting ≥ 1 of the following criteria:

      • At least 30% myeloid blasts in peripheral blood or bone marrow
      • Extramedullary infiltrates of leukemic cells (other than in the spleen or liver) with peripheral blood myeloid blast morphology
    • Acute lymphoblastic leukemia (ALL)

      • Previously treated with standard induction or consolidation chemotherapy
  • Philadelphia chromosome-positive OR BCR-ABL-positive disease
  • Previously treated with imatinib mesylate AND meets 1 of the following criteria:

    • Primary* or acquired** hematologic resistance to imatinib mesylate, defined as 1 of the following:

      • Initial diagnosis of chronic phase CML that progressed to blastic phase CML during treatment with imatinib mesylate at a dose ≥ 400 mg/day
      • Initial diagnosis of accelerated phase CML that progressed to blastic phase CML during treatment with imatinib mesylate at a dose ≥ 600 mg/day (400-599 mg/day in patients intolerant to a dose ≥ 600 mg/day)
      • Initial diagnosis of blastic phase CML, meeting the criteria for blast crisis after ≥ 4 weeks (2 weeks for rapid disease progression) of treatment with imatinib mesylate at a dose ≥ 600 mg/day (400-599 mg/day in patients intolerant to a dose ≥ 600 mg/day)
      • ALL that progressed after OR did not respond to ≥ 4 weeks of treatment with imatinib mesylate at a dose ≥ 600 mg/day (400-599 mg/day in patients intolerant to a dose ≥ 600 mg/day) NOTE: *Disease did not respond to treatment with imatinib mesylate

NOTE: **Disease responded to treatment with imatinib mesylate but subsequently progressed to blastic phase CML

  • Intolerant to imatinib mesylate, defined as toxicity possibly related to treatment with imatinib mesylate at a dose ≤ 400 mg/day that led to discontinuation of therapy

    • Patients who tolerated a dose of imatinib mesylate at 400 mg/day but are intolerant to higher doses are not considered intolerant to imatinib mesylate NOTE: *Imatinib mesylate need not be the most recent treatment for CML or ALL prior to study entry

      • Not eligible for OR unwilling to undergo transplantation

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics
  • No history of significant bleeding disorder unrelated to CML, including any of the following:

    • Diagnosis of congenital bleeding disorder (e.g., von Willebrand's disease)
    • Diagnosis of acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII antibodies)

Hepatic

  • Bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 times ULN

Renal

  • Creatinine ≤ 1.5 times ULN
  • Total or ionized calcium normal* NOTE: *Supplementation allowed

Cardiovascular

  • No myocardial infarction within the past 6 months
  • No uncontrolled angina within the past 3 months
  • No congestive heart failure within the past 3 months
  • No diagnosis or suspicion of congenital long QT syndrome
  • No history of clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
  • No prolonged QTc interval (i.e., > 450 msec) on EKG by Bazett's correction or Fridericia correction
  • No history of second or third degree heart block

    • Patients with pacemakers may be eligible
  • No heart rate consistently < 50 beats/minute on EKG
  • No uncontrolled hypertension
  • No other uncontrolled or significant cardiovascular disease

Gastrointestinal

  • No clinically significant gastrointestinal tract bleeding within the past 6 months
  • No evidence of digestive dysfunction that would preclude study participation

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 1 month before, during, and for at least 3 months after completion of study treatment
  • Potassium normal*
  • Magnesium normal*
  • No other serious uncontrolled medical disorder or active infection that would preclude study participation
  • No dementia or altered mental status that would preclude giving informed consent
  • No evidence of organ dysfunction that would preclude study participation
  • No prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of a psychiatric or physical (e.g., infectious disease) illness
  • No other incurable malignancy NOTE: *Supplementation allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 14 days since prior interferon

Chemotherapy

  • See Disease Characteristics
  • More than 14 days since prior cytarabine
  • Prior or concurrent hydroxyurea allowed for treatment of elevated WBC (i.e., WBC > 50,000/mm^3)

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No prior BMS-354825
  • More than 7 days since prior imatinib mesylate
  • At least 7 days since prior low-dose aspirin (≤ 325 mg/day)
  • At least 14 days since prior high-dose aspirin (> 325 mg/day)
  • More than 14 days since prior targeted small-molecule anticancer agents
  • More than 28 days since prior investigational agents
  • At least 5 days or 5 half-lives (whichever is longer) since prior and no concurrent drugs that may confer a risk of torsades de pointes, including any of the following:

    • 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
  • At least 5 days or 5 half-lives (whichever is longer) since prior and no concurrent medications that directly inhibit platelet function (except anagrelide for treatment of thrombocytosis due to CML), including any of the following:

    • Dipyridamole
    • Epoprostenol
    • Eptifibatide
    • Clopidogrel
    • Cilostazol
    • Abciximab
    • Ticlopidine
  • At least 5 days or 5 half-lives (whichever is longer) since prior and no concurrent anticoagulants (e.g., warfarin or heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin])

    • Concurrent prophylactic low-dose warfarin allowed for prevention of catheter thrombosis or for heparin-flush of IV lines
  • No other concurrent therapy for CML
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00110097

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
Study Chair: Neil P. Shah, MD Jonsson Comprehensive Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Coutre S, Martinelli G, Dombret H, et al.: Dasatanib (D) in patients (pts) with chronic myelogenous leukemia (CML) in lymphoid blast crisis (LB-CML) or Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ALL) who are imatinib (IM)-resistant (IM-R) or intolerant (IM-I): the CA180015 'START-L' study. [Abstract] J Clin Oncol 24 (Suppl 18): A-6528, 344s, 2006.
Ottmann OG, Martinelli G, Dombret H, et al.: A phase II study of dasatinib in patients with chronic myeloid leukemia (CML) in lymphoid blast crisis or Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to imatinib: the 'START-L' CA180015 study. [Abstract] Blood 106 (11): A-42, 2005.

Other Publications:
Publications indexed to this study:
Study ID Numbers: CDR0000422432, UCLA-0411071-01, BMS-CA180015, EUDRACT-2004-002517-36
Study First Received: May 3, 2005
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00110097  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
blastic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
recurrent adult acute lymphoblastic leukemia

Study placed in the following topic categories:
Chromosomal abnormalities
Philadelphia Chromosome
Blast Crisis
Leukemia, Lymphoid
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chronic myelogenous leukemia
Hematologic Diseases
Myeloproliferative Disorders
Leukemia, Myeloid
Recurrence
Acute lymphoblastic leukemia, adult
Imatinib
Lymphatic Diseases
Leukemia
Dasatinib
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosome Aberrations
Lymphoproliferative Disorders
Bone Marrow Diseases
Lymphoma

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Translocation, Genetic
Pharmacologic Actions
Neoplasms
Neoplastic Processes
Pathologic Processes
Therapeutic Uses
Cell Transformation, Neoplastic

ClinicalTrials.gov processed this record on January 16, 2009