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

• Status: Completed
• Trial end date: 2008-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed systemic mastocytosis

• Objective evidence of disease, as defined by the following:

• Hemoglobin < 10 g/dL

• Recurrent mast cell mediator-release symptoms that impair the patient's quality of life

• Symptomatic hepatosplenomegaly

• Ascites

• Symptomatic bone disease

• Profound constitutional symptoms (e.g., fatigue, asthenia, flushing, hyperpyrexia, weight loss, myalgia, and arthralgia)

• Elevated serum tryptase level

• Mast cell leukemia allowed

• Mastocytosis associated with myeloproliferative disease (e.g., hypereosinophilic syndrome or chronic myelomonocytic leukemia) allowed

• Patients with eosinophilia (i.e., absolute eosinophil count ≥ 1,000/mm^3) must be evaluated for the presence or absence of FIP1L1-PDGFRA mutation; if the mutation is absent, the patient is eligible; if the mutation is present, the patient is eligible provided disease is refractory to imatinib mesylate

• 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