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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00268229
First received: December 20, 2005
Last updated: February 12, 2013
Last verified: February 2013
History of Changes
  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 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Maximum tolerated dose of imatinib mesylate at one year [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Non-dose limiting toxicities associated with imatinib mesylate at one year [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: July 2003
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: cytarabine
    300 mg/m2/day
    Drug: daunorubicin hydrochloride
    45 mg/m2/day
    Drug: imatinib mesylate
    dose escalation (300 mg/day to 800 mg/day).
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
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
National Cancer Institute (NCI)
Investigators
Study Chair: Anjali Advani, MD The Cleveland Clinic
  More Information

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

No publications provided

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00268229     History of Changes
Other Study ID Numbers: CASE-CCF-6441, P30CA043703, CASE-CCF-6441
Study First Received: December 20, 2005
Last Updated: February 12, 2013
Health Authority: United States: Federal Government

Keywords provided by The Cleveland Clinic:
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)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Imatinib
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on June 17, 2013