A Multicenter Phase I Trial of 17-N-allylamino-17-demethoxy Geldanamycin (17-AAG, NSC #330507) in Patients With Recurrent/Refractory Pediatric Solid Tumors (Ewing's Sarcoma, Desmoplastic Small Round Cell Tumor, Osteosarcoma, Neuroblastoma, and Rhabdomyosarcoma) and Leukemia
Inclusion Criteria:
- Histologically confirmed diagnosis of 1 of the following malignancies:
- Leukemia
- Lymphoid, myeloid, or mixed lineage
- Relapsed (in second or greater relapse) or refractory disease, confirmed by
1 of the following:
- Bone marrow relapse, defined as either M3 bone marrow (> 25% blasts
in the bone marrow aspirate) OR M2 bone marrow (5-25% blasts in the
bone marrow aspirate) at any time after complete remission is attained
- CNS relapse, defined as at least 5 WBC/mL by cytospin of any
cerebrospinal fluid (CSF) specimen OR less than 5 WBC/mL by cytospin
of 2 consecutive CSF specimens obtained >= 4 weeks apart and having
definitive confirmation that blasts are derived from the original
leukemic clone by molecular cytogenetics, multiparameter flow
cytometry, or immunostaining of >= 2 antigens
- Patients with underlying chronic myeloid leukemia must have > 25% blasts in
the bone marrow aspirate
- Patients with M3 bone marrow AND extramedullary sites of disease, other
than leptomeningeal disease, are eligible
- 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
- Performance status - Karnofsky 70-100% (for patients > 10 years of age)
- Performance status - Lansky 70-100% (for patients =< 10 years of age)
- More than 8 weeks
- Absolute neutrophil count >= 750/mm^3
- Platelet count >= 75,000/mm^3 (transfusion independent)
- Hemoglobin >= 8.5 g/dL (transfusion allowed)
- Bilirubin < 1.5 mg/dL
- ALT and AST =< 2.5 times upper limit of normal (ULN)
- INR =< 1.5 times ULN
- Albumin > 2.0 g/dL
- Creatinine =< 1.5 times ULN for age
- Creatinine clearance or radioisotope glomerular filtration rate > 60 mL/min
- Ejection fraction >= 50%
- Shortening fraction >= 28%
- QTc < 450 msec for men (470 msec for women)
- No congenital long QT syndrome
- LVEF > 40% by MUGA
- No symptomatic congestive heart failure
- No cardiac arrhythmia
- No New York Heart Association class III or IV heart failure
- No myocardial infarction within the past year
- No uncontrolled dysrhythmias
- No poorly controlled angina
- More than 12 months since active ischemic heart disease
- No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular
fibrillation >= 3 beats in a row)
- No left bundle branch block
- No other significant cardiac disease
- No pulmonary fibrosis by radiography
- 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
- 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)
- 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
- 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
- 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
- No prior radiotherapy to the heart
- At least 1 week since prior retinoids
- No concurrent antiretroviral therapy for HIV-positive patients
- No concurrent medication to control arrhythmias
- No concurrent medications that prolong or may prolong QTc interval
- No other concurrent investigational agents
- No other concurrent anticancer therapy
