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

Phase 2
18 Years
Not Enrolling
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Nonneoplastic Condition, Precancerous Condition

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Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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



- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 3 months


- 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)


- AST and ALT ≤ 2 times upper limit of normal (ULN) (< 4 times ULN for patients with

- Bilirubin normal

- Alkaline phosphatase ≤ 3 times ULN


- Creatinine ≤ 1.4 mg/dL OR

- Creatinine clearance ≥ 60 mL/min


- 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


- 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

- 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


- 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


Biologic therapy

- Not specified


- 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


- At least 4 weeks since prior radiotherapy

- No prior radiation that included the heart in the field (e.g., mantle) or chest


- Not specified


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response (complete and partial response)

Safety Issue:


Principal Investigator

Antonio T. Fojo, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Food and Drug Administration

Study ID:




Start Date:

May 2006

Completion Date:

June 2008

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Nonneoplastic Condition
  • Precancerous Condition
  • Waldenström 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 condition
  • Leukemia
  • Lymphoma
  • Mastocytosis
  • Urticaria Pigmentosa
  • Mastocytoma
  • Myeloproliferative Disorders
  • Precancerous Conditions
  • Mastocytosis, Systemic



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182
NCI - Center for Cancer Research Bethesda, Maryland  20892