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

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00132015

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

18.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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 them from dividing.

PURPOSE: This phase II trial is studying how well 17-AAG works in treating patients with systemic mastocytosis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Nonneoplastic Condition Precancerous Condition	Drug: tanespimycin	Phase 2

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, 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Jun 1, 2008

Outcome Measures

Primary Outcome Measures

Objective response (complete and partial response) []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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