Status:
COMPLETED
17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Systemic Mastocytosis
Lead Sponsor:
National Institutes of Health Clinical Center (CC)
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Chronic Myeloproliferative Disorders
Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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 t...
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, ...
Eligibility Criteria
Inclusion
- 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
Exclusion
Key Trial Info
Start Date :
May 1 2006
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 1 2008
Estimated Enrollment :
37 Patients enrolled
Trial Details
Trial ID
NCT00132015
Start Date
May 1 2006
End Date
June 1 2008
Last Update
March 15 2012
Active Locations (2)
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1
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
2
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892