Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI WSU-C-2599 NCI-5932, 5932, NCT00066326

Objectives

1. 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.
2. Determine the pharmacokinetics of this regimen in these patients.

Entry 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

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)

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Barbara Ann Karmanos Cancer Institute

Charles Schiffer, MD, Protocol chair		Ph: 313-576-8737 Email: schiffer@karmanos.org

Registry Information
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
Trial Start Date		2003-06-23
Registered in ClinicalTrials.gov		NCT00066326
Date Submitted to PDQ		2003-06-06
Information Last Verified		2004-10-18
NCI Grant/Contract Number		U01-CA62487

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