Imatinib Mesylate, Daunorubicin, and Cytarabine in Treating Patients With Relapsed Acute Myeloid Leukemia

NCT ID: NCT00268229

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2011-08-31

Brief Summary

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

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) and recommended phase II dose of imatinib mesylate in combination with daunorubicin hydrochloride and cytarabine in patients with relapsed acute myeloid leukemia.

Secondary

• Assess the non-dose-limiting toxicities associated with this regimen in these patients.
• Determine any preliminary evidence of clinical activity of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of imatinib mesylate.

Patients receive daunorubicin IV on days 1-3 and cytarabine IV continuously on days 1-7. Patients also receive oral imatinib mesylate once daily beginning on day 1 and continuing until disease progression or unacceptable toxicity. Patients with persistent leukemia on day 14 bone marrow biopsy but ≥ 50% reduction in bone marrow blasts receive 5 more days of cytarabine and 2 more days of daunorubicin while continuing imatinib mesylate.

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 1 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cytarabine

300 mg/m2/day

Intervention Type: DRUG

daunorubicin hydrochloride

45 mg/m2/day

Intervention Type: DRUG

imatinib mesylate

dose escalation (300 mg/day to 800 mg/day).

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

• At least 20% of peripheral blood or bone marrow blasts positive for c-kit
• No evidence of leptomeningeal involvement

PATIENT CHARACTERISTICS:

• ECOG Performance Status 0-2
• Liver enzymes (AST and ALT) and total bilirubin ≤ 2 times upper limit of normal
• Serum creatinine ≤ 2 times upper limit of normal
• No New York Heart Association grade III or IV cardiac problems

• Defined as congestive heart failure or myocardial infraction within the past 6 months
• No known chronic liver disease (i.e., chronic active hepatitis and cirrhosis)
• No serious or poorly controlled medical conditions that could be exacerbated by the treatment or would seriously complicate compliance with this study
• No other active primary malignancy unless it is not currently clinically significant and does not require active intervention
• No history of HIV infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No significant history of noncompliance to medical regimens or inability to grant reliable informed consent

PRIOR CONCURRENT THERAPY:

• Previous treatment-related toxicities should be resolved
• No other investigational agents within the past 28 days
• No chemotherapy within the past 4 weeks

• 6 weeks for nitrosourea or mitomycin C
• No major surgery within the past 4 weeks
• No concurrent use of the following drugs is allowed: ketoconazole, dilantin, itraconazole, erythromycin, clarithromycin, dexamethasone, rifampin, tegretol, phenobarbital, Hypericum perforatum (St. John's wort), cyclosporine, pimozide, warfarin, certain HMG-CoA reductase inhibitors, traizolo-benzodiazepines, or dihydropyridine calcium channel blockers
• No other concurrent anticancer agents, including chemotherapy and biologic agents
• No other concurrent investigational drugs
• Concurrent medications known to be metabolized by cytochrome p450 enzymes are allowed
• No therapeutic anticoagulation with warfarin will be permitted in patients participating in this study

• Therapeutic anticoagulation may be accomplished using low-molecular weight heparin
• Mini-dose warfarin for prophylaxis of central venous catheter thrombosis allowed
• No concurrent routine use of systemic corticosteroid therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anjali Advani, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CCF-6441

Identifier Type: -

Identifier Source: secondary_id

CASE-CCF-6441

Identifier Type: -

Identifier Source: org_study_id