A Phase I Study of 17-AAG in Relapsed/Refractory Pediatric Patients With Solid Tumors or Leukemia
1 Year
21 Years
Both
Acute Undifferentiated Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of 17-AAG in Relapsed/Refractory Pediatric Patients With Solid Tumors or Leukemia
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and recommended phase II dose of 17-AAG
administered as a 60 or 120-minute intravenous infusion on days 1, 4, 8, and 11, of a 21-day
course, to children with refractory solid tumors or relapsed leukemia.
II. To define and describe the toxicities of 17-AAG administered on this schedule.
III. To characterize the pharmacokinetics of 17-AAG in children with refractory cancer.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of 17-AAG within the confines of a phase I
study.
II. To assess the biologic activity of 17-AAG. III. To examine the role of CYP3A5
polymorphisms in the pharmacologic and clinical phenotypes observed following administration
of 17-AAG to children, within the confines of a phase 1 study.
OUTLINE: This is a dose-escalation, multicenter study.
Patients with solid tumors receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over
60-120 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 17 courses
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 6 patients
experience dose-limiting toxicity. Once the MTD is determined, up to 6 additional patients
with leukemia receive 17-AAG at the MTD as above. If these 6 patients tolerate this regimen,
another 6 leukemia patients receive 17-AAG IV over 60 minutes on days 1, 4, 8, 11, 15, and
18.
Treatment repeats every 28 days for 17 courses in the absence of disease progression or
unacceptable toxicity. Patients are followed at 30 days.
Inclusion Criteria:
- Histologically confirmed diagnosis of solid tumor or leukemia with documented M3
marrow
- Histologic confirmation of intrinsic brain stem tumors not required
- Relapsed or refractory disease
- No known curative therapy
- In patients with CNS tumors, neurologic deficits must be stable for at least the past
week
- Performance status - Karnofsky 50-100% (>10 years of age)
- Performance status - Lansky 50-100% (≤ 10 years of age)
- For patients with solid tumors:
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion independent)
- Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- For patients with leukemia:
- Platelet count ≥ 20,000/mm^3 (may receive platelet transfusions)
- Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 2.5 times ULN
- Albumin ≥ 2 g/dL
- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
- Creatinine based on age as follows:
- ≤ 0.8 mg/dL if ≤ 5 years of age
- ≤ 1.0 mg/dL if > 5 years and ≤ 10 years of age
- ≤ 1.2 mg/dL if > 10 years and ≤ 15 years of age
- ≤ 1.5 mg/dL if > 15 years and ≤ 21 years of age
- No uncontrolled infection
- No prior severe allergy to eggs
- No situation that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- At least 7 days (or window for adverse effects has passed) since prior biologic
therapy and recovered
- At least 7 days since prior hematopoietic growth factors
- At least 2 months since prior stem cell transplantation and no evidence of
graft-vs-host disease
- No concurrent hematopoietic growth factors
- No concurrent biologic therapy
- No concurrent immunotherapy
- At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
and recovered
- No other concurrent chemotherapy
- No concurrent steroid therapy
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 3 months since prior total body irradiation or craniospinal radiotherapy
- At least 3 months since prior radiotherapy to ≥ 50% of the pelvis
- At least 6 weeks since prior substantial bone marrow radiotherapy
- Recovered from prior radiotherapy
- No concurrent radiotherapy
- No other concurrent investigational drugs
- No other concurrent anticancer agents
- No concurrent phenytoin or phenobarbital
- No concurrent warfarin
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
MTD defined as the maximum dose at which fewer than one-third of patients experience DLT
Outcome Time Frame:
21 days
Safety Issue:
Yes
Principal Investigator
Brenda Weigel
Investigator Role:
Principal Investigator
Investigator Affiliation:
COG Phase I Consortium
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01811
NCT ID:
NCT00079404
Start Date:
March 2004
Completion Date:
Related Keywords:
- Acute Undifferentiated Leukemia
- Recurrent Childhood Acute Lymphoblastic Leukemia
- Recurrent Childhood Acute Myeloid Leukemia
- Secondary Acute Myeloid Leukemia
- Unspecified Childhood Solid Tumor, Protocol Specific
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Neoplasms
Name | Location |
|---|---|
| COG Phase I Consortium | Arcadia, California 91006-3776 |
