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

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00345826

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: dasatinib	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2005

Actual Primary Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib	Drug: dasatinib

Arm

Intervention/Treatment

Experimental: Dasatinib

Drug: dasatinib

Outcome Measures

Primary Outcome Measures

Long term safety and tolerability [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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