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

• ClinicalTrials.gov Identifier: NCT00132015
• Recruitment Status: Completed
• First Posted: August 19, 2005
• Last Update Posted: March 15, 2012
• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Information provided by: National Institutes of Health Clinical Center (CC)

Tracking Information

• First Submitted Date: August 16, 2005
• First Posted Date: August 19, 2005
• Last Update Posted Date: March 15, 2012
• Study Start Date: May 2006
• Actual Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 16, 2006): Objective response (complete and partial response)
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: November 16, 2006): 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
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Systemic Mastocytosis
• 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

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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Nonneoplastic Condition
• Precancerous Condition

• Intervention: Drug: tanespimycin
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: November 8, 2006): 37
• Original Enrollment: Not Provided
• Actual Study Completion Date: June 2008
• Actual Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00132015
• Other Study ID Numbers: 060076; 06-C-0076; NCI-6454; NCI-P6175; CDR0000438778
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Antonio T. Fojo, MD, PhD; National Cancer Institute (NCI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: March 2012