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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00345826
• Other study ID #: CDR0000480396
• Secondary ID: UCLA-0509010-01B
• Status: Completed
• Phase: Phase 1
• First received: June 28, 2006
• Last updated: January 7, 2013
• Start date: November 2005

Study information

• Verified date: January 2013
• Source: Jonsson Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• dasatinib

Locations

Country	Name	City	State
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 leuke — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long term safety and tolerability		5 years	Yes