Phase I Study of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients With Imatinib Mesylate-Resistant Chronic Phase Chronic Myelogenous Leukemia
Last Modified: 5/4/2005  First Published: 12/22/2004
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Trial Contact Information Registry Information
Alternate Title
17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate
Basic Trial Information
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Status
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Age
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Sponsor
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Protocol IDs
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Phase I
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Treatment
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Completed
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18 and over
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NCI, Pharmaceutical / Industry
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UCLA-0408048-01 CTC-CNF1010, CTC-CNF1010-CML-04001, NCT00100997
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Objectives Primary - Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), in terms of frequency, severity, and duration of treatment-emergent adverse events, in patients with imatinib mesylate-resistant Philadelphia chromosome (Ph)-positive chronic phase chronic myelogenous leukemia.
- Determine the pharmacokinetics of this drug and its primary metabolite (17-amino-17-demethoxygeldanamycin) in these patients.
Secondary - Determine the hematologic response rate, in terms of WBC count, platelet count, and assessment of blast cells in peripheral blood, in patients treated with this drug.
- Determine the cytogenic response rate, in terms of Ph-positive progenitor cells in the bone marrow, in patients treated with this drug.
- Assess the effect of this drug on pharmacodynamic markers (i.e., CRKL phosphorylation, BCR-ABL kinase activity, and BCR-ABL, RAF kinase, and HSP70 expression) in these patients.
Entry Criteria Disease Characteristics:
Prior/Concurrent Therapy:
Biologic therapy - More than 2 weeks since prior interferon
- No concurrent interferon
Chemotherapy - More than 2 weeks since prior cytarabine (4 weeks for doses > 100 mg)
- More than 6 weeks since prior busulfan
- No concurrent cytarabine
- No concurrent hydroxyurea during the second study treatment course and beyond
- No concurrent anagrelide during the second study treatment course and beyond
Endocrine therapy Radiotherapy Surgery Other - More than 2 days since prior imatinib mesylate
- More than 1 week since prior and no concurrent drugs that alter metabolism by cytochrome P450 3A4, including the following:
- Diltiazem
- Nifedipine
- Verapamil
- Fluconazole
- Itraconazole
- Ketoconazole
- Lovastatin
- Simvastatin
- Indinavir
- Nelfinavir
- Ritonavir
- Alprazolam
- Diazepam
- Midazolam
- Triazolam
- Phenobarbital
- Phenytoin
- Carbamazepine
- Azithromycin
- Clarithromycin
- Erythromycin
- Rifampin
- Rifamycin
- Astemizole
- Terfenidine
- Amiodarone
- Cimetidine
- Cisapride
- Cyclosporine
- Grapefruit juice
- Hypericum perforatum (St. John's wort)
- Warfarin
- More than 4 weeks since prior investigational drugs and recovered
- No concurrent imatinib mesylate
Patient Characteristics:
Age Performance status Life expectancy Hematopoietic - See Disease Characteristics
Hepatic - Bilirubin < 1.5 times ULN (3 mg/dL for patients with Gilbert's syndrome)
- ALT or AST < 2 times ULN
- No known hepatitis positivity
Renal - Creatinine < 1.5 times ULN
OR - Creatinine clearance > 60 mL/min
Cardiovascular - No New York Heart Association class III or IV cardiac disease
Pulmonary - No severe debilitating pulmonary disease, including any of the following:
- Dyspnea at rest
- Significant shortness of breath
- Chronic obstructive pulmonary disease
Other - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 1 month after study participation
- No known HIV positivity
- No psychological or social condition that would preclude study compliance
- No addictive disorder that would preclude study compliance
- No family problems that would preclude study compliance
- No known allergy or sensitivity to soy or other excipient components of study drug
- No other illness or condition that may affect safety of study treatment or evaluation of study endpoints
Expected Enrollment Approximately 40 patients will be accrued for this study. Outline This is an open label, dose-escalation, multicenter study. Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 15 minutes or 1 hour (depending on the dose administered) once on days 1, 4, 8, 11, 15, 18, 22, and 25. Treatment repeats every 28 days for up to 3 courses in the absence of unacceptable toxicity or disease progression. Eligible patients may receive additional courses of 17-AAG at the discretion of the investigator. 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. Up to 10 additional patients are treated at the MTD. Patients are followed for 1 month.
Trial Contact Information
Trial Lead Organizations Jonsson Comprehensive Cancer Center at UCLA | | | Charles Sawyers, MD, Protocol chair | | Ph: 310-206-5585; 888-798-0719 |
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Registry Information | | Official Title | | A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered CNF1010 )17-(Allylamino)-17-Demethoxygeldanamycin [17-AAG]) in Patients With Gleevec-Resistent Chronic Myelogenous Leukemia | | Trial Start Date | | 2004-10-26 | | Registered in ClinicalTrials.gov | | NCT00100997 1 | | Date Submitted to PDQ | | 2004-11-15 | | Information Last Verified | | 2005-05-04 | | NCI Grant/Contract Number | | P30-CA16042 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.
Table of Links
1 | http://clinicaltrials.gov/ct/show/NCT00100997 |
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