Cladribine, Cytarabine, and Imatinib Mesylate in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Blastic Phase Chronic Myelogenous Leukemia

Sponsor

University of Rochester (Other)

Overall Status

Completed

CT.gov ID

NCT00258271

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cladribine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cladribine and cytarabine together with imatinib mesylate may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with cladribine and cytarabine in treating patients with refractory or relapsed acute myeloid leukemia or blastic phase chronic myelogenous leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: filgrastim Drug: cladribine Drug: cytarabine Drug: imatinib mesylate	Phase 1

Detailed Description

OBJECTIVES:

Determine the safety and feasibility of cladribine, cytarabine, and imatinib mesylate in patients with refractory or relapsed acute myeloid leukemia or blastic phase chronic myelogenous leukemia.
Determine the maximum tolerated dose of imatinib mesylate in patients treated with this regimen.
Correlate the expression of c-kit and the presence of c-kit mutations with clinical response in patients treated with this regimen.
Correlate the in vitro inhibitory effects of imatinib mesylate and cytarabine on the proliferation and survival of leukemic cells with clinical response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of imatinib mesylate.

Patients receive oral imatinib mesylate once daily on days 1-15 and cladribine IV over 2 hours and cytarabine IV over 4 hours on days 3-7. Patients also receive filgrastim (G-CSF) subcutaneously on days 2-7. Treatment repeats every 15 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically for up to 1 year.

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Primary Purpose:

Treatment

Official Title:

A Phase I Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Leukemias

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of acute myeloid leukemia (AML) or blastic phase chronic myelogenous leukemia (CML)
Refractory AML defined as any of the following:
Failure to achieve complete response (CR) after 2 courses of induction chemotherapy
Persistent bone marrow blasts > 40% after 1 course of induction chemotherapy
Relapse of disease within 3 months since CR
Relapsed AML defined as the following:
Any evidence of disease recurrence after CR (early relapse occurs within 3-12 months and late relapse occurs > 12 months later)
No acute promyelocytic leukemia (AML-M3 FAB subgroup)

PATIENT CHARACTERISTICS:

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin ≤ 2.0 mg/dL
AST ≤ 2.5 times upper limit of normal
No known chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

Renal

Creatinine < 2.5 mg/dL (if 2.0-2.5 mg/dL, glomerular filtration rate must be measured and dose of cytarabine adjusted if necessary)

Cardiovascular

No New York Heart Association grade III-IV heart disease
No congestive heart failure
No myocardial infarction within the past 6 months
Ejection fraction ≥ 30%

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment
No uncontrolled systemic active infection
No known HIV infection
No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
No history of other curatively treated malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

No other concurrent biologic agents

Chemotherapy

See Disease Characteristics
No other concurrent chemotherapy

Endocrine therapy

No concurrent birth control pills

Other

More than 1 week since any prior investigational agent
No other concurrent investigational agents or therapies
No other concurrent anticancer agents
No concurrent therapeutic anticoagulation with warfarin
Low molecular weight heparin or heparin allowed for therapeutic anticoagulation
Mini-dose warfarin (e.g., 1 mg per day) allowed for prophylaxis of central venous catheter thrombosis