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

Sponsor

Barbara Ann Karmanos Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00066326

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: imatinib mesylate Drug: tanespimycin	Phase 1

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study Of The Combination Of 17-AAG And Imatinib Mesylate (Gleevec) In Patients With Blastic Phase, Accelerated Phase Of Chronic Mesylate Leukemia (CML) Or Patients With Chronic Phase CML Who Have Not Achieved A Cytogenetic Response With Imatinib Mesylate

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Oct 1, 2004

Actual Study Completion Date :

Sep 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)