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

Phase 1
18 Years
Open (Enrolling)

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Trial Information

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


- 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.

Inclusion Criteria


- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Camille Abboud, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

James P. Wilmot Cancer Center



Study ID:




Start Date:

March 2005

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent adult acute myeloid leukemia
  • adult acute basophilic leukemia
  • adult acute eosinophilic leukemia
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • blastic phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • Blast Crisis
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester, New York  14642