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

NeuroTherapia, Inc.

Status and phase

Completed

Phase 1

Conditions

Leukemia

Treatments

Drug: imatinib mesylate

Drug: daunorubicin hydrochloride

Drug: cytarabine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00268229

P30CA043703 (U.S. NIH Grant/Contract)

CASE-CCF-6441

Details and patient eligibility

About

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.

Full 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.

Enrollment

21 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Bone marrow biopsy confirming acute myeloid leukemia (AML)
- No M3 AML
Patient must have relapsed to standard chemotherapy
- Patients who relapse within six months of response to treatment or those who never responded to an anthracycline/cytarabine combination will be excluded
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