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

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00100997

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: tanespimycin	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Oct 1, 2004

Actual Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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