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

Conditions:Blood Cancer, Hematology, Leukemia
Therapuetic Areas:Hematology, Oncology
Age Range:18 - Any
Start Date:March 2005

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

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.


- 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

- 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.


- 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

- Persistent bone marrow blasts > 40% after 1 course of induction

- 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)


Performance status

- ECOG 0-2

Life expectancy

- Not specified


- Not specified


- 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)


- 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)


- 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%


- 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


Biologic therapy

- No other concurrent biologic agents


- See Disease Characteristics

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent birth control pills


- 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
We found this trial at
601 Elmwood Avenue
Rochester, New York 14642
(585) 275-5830
James P. Wilmot Cancer Center at University of Rochester Medical Center The Wilmot Cancer Center...
Rochester, NY
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