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

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
dasatinib
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, recurrent adult acute lymphoblastic leukemia, chronic myelogenous leukemia, BCR-ABL1 positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Jonsson Comprehensive Cancer Center at UCLA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dasatinib

Arm Description

Outcomes

Primary Outcome Measures

Long term safety and tolerability

Secondary Outcome Measures

Full Information

First Posted
June 28, 2006
Last Updated
January 7, 2013
Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00345826
Brief Title
Dasatinib in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia
Official Title
Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Subjects Who Experienced Clinical Benefit on Protocol CA 180-002
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, recurrent adult acute lymphoblastic leukemia, chronic myelogenous leukemia, BCR-ABL1 positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dasatinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
dasatinib
Primary Outcome Measure Information:
Title
Long term safety and tolerability
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Sawyers, MD
Organizational Affiliation
Jonsson Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16775234
Citation
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.
Results Reference
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Dasatinib in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia

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