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17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Systemic Mastocytosis
This study has been completed.
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00132015
  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
Multicentric Castleman Disease
Precancerous/Nonmalignant Condition
Drug: tanespimycin
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: IPI-504 17-(Allylamino)-17-demethoxygeldanamycin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

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
Primary Completion Date: June 2008 (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
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

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
Web site for additional information  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000438778, NCI-06-C-0076, NCI-6454, NCI-P6175
Study First Received: August 16, 2005
Last Updated: December 13, 2008
ClinicalTrials.gov Identifier: NCT00132015  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
Waldenstrom macroglobulinemia
multicentric Castleman disease
unicentric Castleman disease
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/nonmalignant condition

Study placed in the following topic categories:
Polycythemia
Giant Lymph Node Hyperplasia
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Mast cell disease
Lymphoma, large-cell, immunoblastic
Lymphomatoid granulomatosis
Neoplasms, Connective and Soft Tissue
Leukemia, Lymphocytic, Chronic, B-Cell
Hemorrhagic thrombocythemia
Thrombocythemia, Hemorrhagic
Chronic lymphocytic leukemia
Essential thrombocytosis
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Myeloproliferative Disorders
Waldenstrom Macroglobulinemia
Mastocytosis
Lymphoma, Non-Hodgkin
Hairy cell leukemia
Multi-centric Castleman’s Disease
Monoclonal gammopathy of undetermined significance
Precancerous Conditions
Lymphoma, Follicular
Lymphoma, large-cell
Burkitt's lymphoma
Leukemia
Lymphoma, Large-Cell, Immunoblastic

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Immune System Diseases
Neoplasms, Connective Tissue

ClinicalTrials.gov processed this record on January 14, 2009