Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as 17-N-allylamino-17-demethoxygeldanamycin use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with imatinib mesylate in treating patients with chronic myelogenous leukemia.

Further Study Information

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with imatinib mesylate in patients with chronic myelogenous leukemia.

• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Patients receive oral imatinib mesylate on days 1-21 and 17-AAG IV over 1 hour on days 1, 4, 8, and 12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6-10 patients receives treatment at the recommended phase II dose.

PROJECTED ACCRUAL: Approximately 21-42 patients will be accrued for this study within 1.5 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia, including any of the following phases:

• Blastic phase

• Greater than 30% blasts in the peripheral blood or bone marrow

• Previously untreated disease OR refractory to or relapsed after most recent therapy

• Accelerated phase, defined by 1 of the following:

• At least 15, but less than 30%, blasts in the peripheral blood or bone marrow

• At least 30% blasts and promyelocytes in the peripheral blood or bone marrow

• Greater than 20% peripheral blood basophilia

• Chronic phase

• No major cytogenetic response (less than 65% Philadelphia chromosome negative) after 12 months of prior imatinib mesylate therapy

• Philadelphia chromosome positive by routine cytogenetics

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 1.5 mg/dL

• ALT and AST no greater than 2.5 times upper limit of normal

Renal

• Creatinine less than 1.5 mg/dL

Cardiovascular

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No known allergy to eggs

• Able to swallow pills

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study compliance

• No other concurrent uncontrolled medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior stem cell transplantation

Chemotherapy

• More than 4 weeks since prior chemotherapy (except hydroxyurea or anagrelide) (at least 6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• No prior liver, kidney, or lung transplantation

• More than 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)

Other

• Prior imatinib mesylate administered within the past 4 weeks is allowed

• No concurrent tacrolimus or cyclosporine as immunosuppressive agents

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent agents that alter CYP3A4 activity, including any of the following:

• Grapefruit juice

• Ketoconazole

• Fluconazole

• Itraconazole

• Erythromycin

• Clarithromycin

• Cimetidine

• Terfenadine

• Astemizole

• HIV protease inhibitors (e.g., indinavir and nelfinavir)

Trial Contact Information

Trial Lead Organizations/Sponsors

Barbara Ann Karmanos Cancer Institute

Charles A. Schiffer

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00066326
Information obtained from ClinicalTrials.gov on December 14, 2011

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