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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066326
• Other study ID #: CDR0000315521
• Secondary ID: U01CA062487P30CA
• Status: Completed
• Phase: Phase 1
• First received: August 6, 2003
• Last updated: April 3, 2013
• Start date: June 2003
• Est. completion date: September 2005

Study information

• Verified date: April 2013
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: September 2005
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• imatinib mesylate

• tanespimycin

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,