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

NCT ID: NCT00345826

Last Updated: 2013-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30

Brief Summary

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.

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.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

Interventions

dasatinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Sawyers, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 16775234 (View on PubMed)

Other Identifiers

UCLA-0509010-01

Identifier Type: -

Identifier Source: secondary_id

BMS-CA180039

Identifier Type: -

Identifier Source: secondary_id

CDR0000480396

Identifier Type: -

Identifier Source: org_study_id