RATIONALE: Drugs used in chemotherapy, such as trimetrexate glucuronate and leucovorin, use
different ways to stop cancer cells from dividing so they stop growing or die. Combining
more than one drug may kill more cancer cells.
PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating
children with recurrent acute lymphoblastic leukemia, recurrent osteosarcoma, or refractory
- Determine the efficacy of trimetrexate glucuronate with leucovorin calcium rescue in
children with recurrent acute lymphoblastic leukemia, recurrent osteogenic sarcoma, or
refractory non-Hodgkin's lymphoma resistant to methotrexate.
- Evaluate the toxicity of this treatment regimen in this patient population.
OUTLINE: Patients are stratified according to disease (acute lymphocytic leukemia,
non-Hodgkin's lymphoma vs osteogenic sarcoma).
Patients receive trimetrexate glucuronate orally or IV every 12 hours on days 1-21 and oral
leucovorin calcium every 12 hours on days 1-24. Treatment repeats every 4 weeks. Patients
with stable or responsive disease may receive up to 4 courses of therapy.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 2 years.
- Histologic evidence of one of the following malignancies that has failed conventional
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma with bone marrow involvement
- Osteogenic sarcoma
- In vitro transport resistance to methotrexate demonstrated by bone marrow aspirate
- 21 and under at diagnosis
- ECOG 0-2
- At least 8 weeks
- Granulocytopenia allowed with bone marrow involvement
- Thrombocytopenia allowed with bone marrow involvement
- Anemia allowed with bone marrow involvement
- (unless due to disease)
- Bilirubin no greater than 2.0 mg/dL
- AST no greater than 100
- Creatinine less than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
- No other serious medical illness
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- Prior bone marrow transplantation allowed
- At least 1 week since prior intrathecal treatment
- At least 2 weeks since prior systemic chemotherapy and recovered
- At least 10 days for rapidly proliferating leukemia (i.e., WBC greater than
- No concurrent chemotherapy
- Not specified
- Prior radiotherapy allowed and recovered
- No concurrent radiotherapy
- Not specified