Imatinib Mesylate and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Myelogenous Leukemia

NCT ID: NCT00066326

Last Updated: 2013-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2005-09-30

Brief 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.

Detailed Description

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.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

imatinib mesylate

Intervention Type: DRUG

tanespimycin

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles A. Schiffer, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Other Identifiers

U01CA062487

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-C-2599

Identifier Type: -

Identifier Source: secondary_id

NCI-5932

Identifier Type: -

Identifier Source: secondary_id

CDR0000315521

Identifier Type: -

Identifier Source: org_study_id