17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with chronic phase chronic myelogenous leukemia that did not respond to imatinib mesylate.

Detailed Description
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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. 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. PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

Official Title
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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

Conditions
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Leukemia

Intervention / Treatment
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* Drug: tanespimycin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of chronic phase chronic myelogenous leukemia Philadelphia chromosome (Ph)-positive disease Hematologic resistence after treatment with imatinib mesylate (400 mg per day or maximum tolerated dose [MTD]) as defined by 1 of the following criteria: Loss of complete hematologic response, defined as WBC count OR platelet count > upper limit of normal (ULN) on 2 separate occasions at least 2 weeks apart that cannot be attributed to other etiologies Absolute increase of ≥ 30% in Ph-positive cells while on a stable dose of imatinib mesylate for at least 6 months* NOTE: *Patients meeting this criterion are not eligible for enrollment into the expanded MTD cohort Less than 15% blasts in peripheral blood or bone marrow AND < 30% blasts and promyelocytes in peripheral blood or bone marrow PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 6 months 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 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 Not specified Radiotherapy Not specified Surgery Not specified 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tanespimycin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic myelogenous leukemia, BCR-ABL1 positive, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia