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

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