17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Systemic Mastocytosis

NCT ID: NCT00132015

Last Updated: 2012-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2008-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well 17-AAG works in treating patients with systemic mastocytosis.

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), in terms of decreases in the number of mast cells in the bone marrow and in serum tryptase levels, in patients with systemic mastocytosis.

Secondary

• Determine the quality of life of patients treated with this drug.
• Determine hematological and non-hematological toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2-6 hours on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive at least 2 additional courses beyond CR. Patients achieving a partial response receive at least 4 additional courses beyond their maximum response. Selected patients may receive additional courses of therapy beyond the protocol guidelines at the discretion of the principal investigator.

Quality of life is assessed at baseline and before each treatment course.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within approximately 10-18 months.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Nonneoplastic Condition; Precancerous Condition

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

tanespimycin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with indolent disease must have a serum tryptase level ≥ 50 ng/mL OR episodes of anaphylaxis that occur with a frequency of > 1 per month

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• See Disease Characteristics
• Platelet count ≥ 100,000/mm^3 (> 25,000/mm^3 for patients with organomegaly)
• Absolute granulocyte count ≥ 1,500/mm^3(> 750/mm^3 for patients with organomegaly)

Hepatic

• AST and ALT ≤ 2 times upper limit of normal (ULN) (< 4 times ULN for patients with hepatomegaly)
• Bilirubin normal
• Alkaline phosphatase ≤ 3 times ULN

Renal

• Creatinine ≤ 1.4 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No New York Heart Association class III-IV congestive heart failure
• No history of myocardial infarction within the past year
• No history of uncontrolled dysrhythmia
• No uncontrolled angina
• No ischemic heart disease within the past 12 months
• No congenital long QT syndrome
• No left bundle branch block
• No serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• QTc interval < 450 msec for males or 470 msec for females
• LVEF > 40% by MUGA
• MUGA or echocardiogram normal
• No prior history of cardiac toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)
• No cardiac symptoms ≥ grade 2
• No other significant cardiac disease

Pulmonary

• No symptomatic pulmonary disease requiring medication including any of the following:

• Dyspnea on or off exertion
• Paroxysmal nocturnal dyspnea
• Requirement for oxygen
• Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease)
• No home oxygen meeting the Medicare requirement
• No compromised pulmonary status (i.e., DLCO ≤ 80%)
• No prior history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)
• No pulmonary symptoms ≥ grade 2

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• HIV negative
• No active uncontrolled infection
• No serious medical illness
• No other non-malignant systemic disease
• No history of serious allergic reaction to eggs
• No other malignancy within the past 2 years except dermatological cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy

Endocrine therapy

• Steroids allowed provided tapering to the lowest level possible to treat thrombocytopenia, diarrhea, or malabsorption symptoms of systemic mastocytosis

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No prior radiation that included the heart in the field (e.g., mantle) or chest

Surgery

• Not specified

Other

• At least 4 weeks since prior tyrosine kinase inhibitors
• No concurrent complimentary or alternative medications* including, but not limited to, the following:

• Hypericum perforatum (St. John's wort)
• Milk thistle
• Kava kava
• Mistletoe extract
• No concurrent agents that cause QTc prolongation
• No concurrent antiarrhythmic therapy
• No other concurrent investigational therapy NOTE: *Unless approved by the investigator

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Principal Investigators

Antonio T. Fojo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

NCI - Center for Cancer Research

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

06-C-0076

Identifier Type: -

Identifier Source: secondary_id

NCI-6454

Identifier Type: -

Identifier Source: secondary_id

NCI-P6175

Identifier Type: -

Identifier Source: secondary_id

CDR0000438778

Identifier Type: -

Identifier Source: secondary_id

060076

Identifier Type: -

Identifier Source: org_study_id

NCT00285311

Identifier Type: -

Identifier Source: nct_alias