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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Clinical Trial of 17-(Allylamino)-17- Demethoxygeldanamycin (17-AAG, NSC 330507 and EPL Diluent, NSC 704057) in Adults With Systemic Mastocytosis

Conditions
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Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Nonneoplastic Condition, Precancerous Condition

Intervention / Treatment
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* Drug: tanespimycin


Participation Criteria
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Eligibility Criteria
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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

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 |
| --- | --- | --- |
| Objective response (complete and partial response) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life as assessed by the European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at baseline and prior to each treatment course |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenström macroglobulinemia, multicentric Castleman disease, unicentric Castleman disease, adult grade III lymphomatoid granulomatosis, polycythemia vera, essential thrombocythemia, hairy cell leukemia, monoclonal gammopathy of undetermined significance, adult Burkitt lymphoma, adult diffuse large cell lymphoma, adult diffuse mixed cell lymphoma, adult diffuse small cleaved cell lymphoma, adult immunoblastic large cell lymphoma, adult lymphoblastic lymphoma, grade 1 follicular lymphoma, grade 2 follicular lymphoma, grade 3 follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, precancerous condition