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
18 Years
N/A
Both
Leukemia
Trial Information
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
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.
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)
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Charles A. Schiffer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000315521
NCT ID:
NCT00066326
Start Date:
June 2003
Completion Date:
September 2005
Related Keywords:
- Leukemia
- blastic phase chronic myelogenous leukemia
- Philadelphia chromosome positive chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- accelerated phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Name | Location |
|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
