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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00132015
First received: August 16, 2005
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Nonneoplastic Condition
Precancerous Condition
Drug: tanespimycin
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Objective response (complete and partial response) [ Designated as safety issue: No ]

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 [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: May 2006
Study Completion Date: June 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00132015

Locations
United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Antonio T. Fojo, MD, PhD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00132015     History of Changes
Obsolete Identifiers: NCT00285311
Other Study ID Numbers: 060076, 06-C-0076, NCI-6454, NCI-P6175, CDR0000438778
Study First Received: August 16, 2005
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
multicentric Castleman disease
unicentric Castleman disease
Waldenström macroglobulinemia
adult grade III lymphomatoid granulomatosis
polycythemia vera
essential thrombocythemia
hairy cell leukemia
monoclonal gammopathy of undetermined significance
adult Burkitt lymphoma
adult diffuse large cell lymphoma
adult diffuse mixed cell lymphoma
adult diffuse small cleaved cell lymphoma
adult immunoblastic large cell lymphoma
adult lymphoblastic lymphoma
grade 1 follicular lymphoma
grade 2 follicular lymphoma
grade 3 follicular lymphoma
mantle cell lymphoma
marginal zone lymphoma
small lymphocytic lymphoma
precancerous condition

Additional relevant MeSH terms:
Leukemia
Lymphoma
Mastocytosis
Urticaria Pigmentosa
Myeloproliferative Disorders
Precancerous Conditions
Mastocytosis, Systemic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Mastocytosis, Cutaneous
Pigmentation Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on July 24, 2014