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

Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Subjects Who Experienced Clinical Benefit on Protocol CA 180-002

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.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: 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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib	Drug: dasatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Long term safety and tolerability	5 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles Sawyers, MD, Jonsson Comprehensive Cancer Center

Publications and helpful links

General Publications

• Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O'Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006 Jun 15;354(24):2531-41. doi: 10.1056/NEJMoa055229.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: June 28, 2006
• First Submitted That Met QC Criteria: June 28, 2006
• First Posted (Estimate): June 29, 2006

Study Record Updates

• Last Update Posted (Estimate): January 8, 2013
• Last Update Submitted That Met QC Criteria: January 7, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: chronic phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic myelogenous leukemia, BCR-ABL1 positive; recurrent adult acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: CDR0000480396; UCLA-0509010-01; BMS-CA180039