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

Leukemia Clinical Trial

Official title:

A Phase I Trial of Imatinib Mesylate (Gleevec, Formerly Known as STI571) in Combination With Daunorubicin and Cytarabine for C-kit Positive Relapsed AML

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00268229
• Other study ID #: CASE-CCF-6441
• Secondary ID: P30CA043703CASE-
• Status: Completed
• Phase: Phase 1
• First received: December 20, 2005
• Last updated: February 12, 2013
• Start date: July 2003
• Est. completion date: August 2011

Study information

• Verified date: February 2013
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cytarabine
300 mg/m2/day
• daunorubicin hydrochloride
45 mg/m2/day
• imatinib mesylate
dose escalation (300 mg/day to 800 mg/day).

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of imatinib mesylate at one year		1 year	Yes
Secondary	Non-dose limiting toxicities associated with imatinib mesylate at one year		1 year	Yes