A Phase I Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Leukemias
18 Years
N/A
Both
Leukemia
Trial Information
A Phase I Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Leukemias
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Camille Abboud, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
James P. Wilmot Cancer Center
Authority:
Unspecified
Study ID:
CDR0000448638
NCT ID:
NCT00258271
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
Name | Location |
|---|---|
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
