A Phase II Clinical Trial of 17-(Allylamino)-17- Demethoxygeldanamycin (17-AAG, NSC 330507 and EPL Diluent, NSC 704057) in Adults With Systemic Mastocytosis
A Phase II Clinical Trial of 17-(Allylamino)-17- Demethoxygeldanamycin (17-AAG, NSC 330507 and EPL Diluent, NSC 704057) in Adults With Systemic Mastocytosis
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.
OBJECTIVES:
Primary
Secondary
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.
DISEASE CHARACTERISTICS:
Histologically confirmed systemic mastocytosis
Objective evidence of disease, as defined by the following:
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
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
No symptomatic pulmonary disease requiring medication including any of the following:
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
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Other
At least 4 weeks since prior tyrosine kinase inhibitors
No concurrent complimentary or alternative medications* including, but not limited to, the following:
No concurrent agents that cause QTc prolongation
No concurrent antiarrhythmic therapy
No other concurrent investigational therapy NOTE: *Unless approved by the investigator