17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors
This study is currently recruiting patients.
Sponsored by: |
Memorial Sloan-Kettering Cancer Center
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Information provided by: |
National Cancer Institute (NCI) |
Purpose
RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop cancer
cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of 17-N-allylamino-17-demethoxygeldanamycin in treating young patients who
have recurrent or refractory leukemia or selected solid tumors.
Condition
|
Treatment or Intervention |
Phase |
Ewing's family of tumors childhood rhabdomyosarcoma childhood soft tissue sarcoma hematopoietic and lymphoid cancer Neuroblastoma Osteosarcoma
|
Drug: 17-N-allylamino-17-demethoxygeldanamycin Procedure: chemotherapy
|
Phase I
|
MedlinePlus related topics: Blood and Blood Disorders; Bone Cancer; Cancer; Cancer Alternative Therapy; Neuroblastoma; Soft Tissue Sarcoma
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Pediatric Patients With Recurrent or Refractory Leukemia
or Selected Solid Tumors
Further Study Details:
OBJECTIVES: Primary
- Determine the dose-limiting toxicity and maximum tolerated dose (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
in pediatric patients with recurrent or refractory leukemia or selected solid tumors.
- Determine the levels of key proteins known to influence cancer cell survival and proliferation in patients treated with this
drug at the MTD.
Secondary
- Determine the pharmacokinetics of this drug in these patients.
- Correlate the alteration of fludeoxyglucose F18 accumulation with tumor response in patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (leukemia vs solid tumor).
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1 hour on days 1, 4, 8, and 11 (for patients with
solid tumors) OR days 1, 4, 8, 11, 14, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 15 patients
are treated at the MTD.
Patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 70 patients (35 per stratum) will be accrued for this study within 23.3-35 months.
Eligibility
Ages Eligible for Study:
up to 21 Years,
Genders Eligible for Study:
Both
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following malignancies:
- Leukemia
- Lymphoid, myeloid, or mixed lineage
- Relapsed or refractory disease confirmed by M3 bone marrow, defined as > 25% blasts in the bone marrow aspirate (including
patients with underlying chronic myeloid leukemia)
- Extramedullary sites of disease, other than leptomeningeal disease, allowed
- In second or greater relapse
- Solid tumor
- One of the following tumor types:
- Neuroblastoma
- Ewing's sarcoma
- Osteosarcoma
- Desmoplastic small round cell tumor
- Rhabdomyosarcoma
- Progressed after prior standard therapy OR no effective standard therapy exists
- Measurable or nonmeasurable disease
- No known brain metastases
- No active leptomeningeal leukemia, defined by the following criteria:
- WBC > 5/mm^3 in cerebrospinal fluid (CSF)
- Unequivocal confirmation of leukemic blasts in CSF by cell morphology
- No symptomatic CNS disease (e.g., cranial nerve abnormalities) without cytologic abnormality in CSF
PATIENT CHARACTERISTICS: Age
- 21 and under at diagnosis
Performance status
- Karnofsky 70-100% (for patients > 10 years of age)
- Lansky 70-100% (for patients ≤ 10 years of age)
Life expectancy
Hematopoietic
- See Disease Characteristics
- Absolute neutrophil count ≥ 750/mm^3*
- Platelet count ≥ 75,000/mm^3* (transfusion independent)
- Hemoglobin ≥ 8.5 g/dL* (transfusion allowed) NOTE: *For patients with solid tumors
Hepatic
- Bilirubin < 1.5 mg/dL
- ALT and AST normal
- INR ≤ 1.5 times upper limit of normal (ULN)
- Albumin > 2.0 g/dL
Renal
- Creatinine ≤ 1.5 times ULN for age OR
- Creatinine clearance or radioisotope glomerular filtration rate > 60 mL/min
Cardiovascular
- Ejection fraction ≥ 50% OR
- Shortening fraction ≥ 28%
- No symptomatic congestive heart failure
- No cardiac arrhythmia
Pulmonary
- No pulmonary fibrosis by radiography
Other
- No ongoing or active bacterial or fungal infection
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- No history of serious allergic reaction attributed to eggs or dimethyl sulfoxide
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy
- Recovered from all immunotherapy
- At least 6 months since prior allogeneic stem cell transplantation*
- At least 3 months since prior autologous stem cell transplantation*
- At least 2 weeks since prior biologic agents (e.g., monoclonal antibodies)
- At least 1 week since prior filgrastim (G-CSF) or sargramostim (GM-CSF) NOTE: *Patients who have had prior stem cell transplantation
must not require immunosuppressive therapy and have no evidence of graft-versus-host disease
Chemotherapy
- Recovered from all prior chemotherapy
- At least 2 weeks since prior chemotherapy (for patients with leukemia only)
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) (for patients with solid tumors)
- No prior oxaliplatin
Endocrine therapy
- No concurrent corticosteroids except for the treatment of adrenal crises in patients with suppressed hypothalamic-pituitary-adrenal
axis response OR for treatment of allergic reactions to medications or blood products
Radiotherapy
- Recovered from all prior radiotherapy
- At least 6 months since prior radiotherapy to ≥ 50% of the pelvis
- At least 6 months since prior radiotherapy to substantial bone marrow, including total body irradiation
- At least 4 weeks since prior local (small port) radiotherapy
Surgery
Other
- At least 1 week since prior retinoids
- No other concurrent investigational agents
- No concurrent antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
Location
and Contact
Information
Arizona Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,
Arizona,
85724,
United States; Recruiting
Rochelle Bagatell, MD
520-626-4851
Phoenix Children's Hospital, Phoenix,
Arizona,
85016,
United States; Recruiting
Jessica Boklan, MD
602-546-0920
Colorado University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,
Colorado,
80218,
United States; Recruiting
Florida Shands Cancer Center at the University of Florida Health Science Center, Gainesville,
Florida,
32610-0296,
United States; Recruiting
Georgia AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus, Atlanta,
Georgia,
30322,
United States; Recruiting
Howard M. Katzenstein, MD
404-727-4451
Maryland Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,
Maryland,
21231-7223,
United States; Recruiting
New York Memorial Sloan-Kettering Cancer Center, New York,
New York,
10021,
United States; Recruiting
Tanya Trippett, MD
212-639-8267
Tennessee Vanderbilt Children's Hospital, Nashville,
Tennessee,
37232-6310,
United States; Recruiting
James A. Whitlock, MD
615-936-1762
Texas University of Texas - MD Anderson Cancer Center, Houston,
Texas,
77030-4009,
United States; Recruiting
Study chairs or principal investigators
Tanya Trippett, MD, Study Chair, Memorial Sloan-Kettering Cancer Center
More Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Study ID Numbers:
CDR0000391010; MSKCC-04069; NCI-6323; POETIC-MSKCC-04069
Record last reviewed:
September 2004
Record first received:
October 6, 2004
ClinicalTrials.gov Identifier:
NCT00093821Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-22