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

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

Tracking Information
First Submitted Date  ICMJE August 16, 2005
First Posted Date  ICMJE August 19, 2005
Last Update Posted Date March 15, 2012
Study Start Date  ICMJE May 2006
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2006)
Objective response (complete and partial response)
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Systemic Mastocytosis
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Nonneoplastic Condition
  • Precancerous Condition
Intervention  ICMJE Drug: tanespimycin
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
37
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2008
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00132015
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institutes of Health Clinical Center (CC)
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Antonio T. Fojo, MD, PhD National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP