Imatinib Mesylate, Daunorubicin, and Cytarabine in Treating Patients With Relapsed Acute Myeloid Leukemia - Full Text View

Sponsored by:	Case Comprehensive Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00268229

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: cytarabine Drug: daunorubicin hydrochloride Drug: imatinib mesylate	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine Cytarabine hydrochloride Daunorubicin hydrochloride Daunorubicin Imatinib Imatinib mesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of imatinib mesylate at one year [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Non-dose limiting toxicities associated with imatinib mesylate at one year [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	July 2003
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00268229

Locations

United States, Ohio
Cleveland Clinic Taussig Cancer Center	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Clinical Trials Office - Cleveland Clinic Taussig Cancer Cente 866-223-8100

Sponsors and Collaborators

Case Comprehensive Cancer Center

Investigators

Study Chair:

Anjali Advani, MD

The Cleveland Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000446305, CASE-CCF-6441
Study First Received:	December 20, 2005
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00268229
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute megakaryoblastic leukemia (M7)

adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Daunorubicin
Acute myelogenous leukemia
Acute myelomonocytic leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Di Guglielmo's syndrome
Recurrence
Imatinib

Leukemia, Myelomonocytic, Acute
Leukemia
Leukemia, Erythroblastic, Acute
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Congenital Abnormalities
Acute monoblastic leukemia
Acute myelocytic leukemia
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009