Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia, Osteosarcoma, or Non-Hodgkin's Lymphoma

OBJECTIVES:

• 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.

DISEASE CHARACTERISTICS:

• Histologic evidence of one of the following malignancies that has failed conventional therapy:

• Acute lymphoblastic leukemia
• Non-Hodgkin's lymphoma with bone marrow involvement
• Osteogenic sarcoma
• In vitro transport resistance to methotrexate demonstrated by bone marrow aspirate assay

PATIENT CHARACTERISTICS:

Age:

• 21 and under at diagnosis

Performance status:

• ECOG 0-2

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Granulocytopenia allowed with bone marrow involvement
• Thrombocytopenia allowed with bone marrow involvement
• Anemia allowed with bone marrow involvement

Hepatic:

• (unless due to disease)
• Bilirubin no greater than 2.0 mg/dL
• AST no greater than 100

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Other:

• No other serious medical illness
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior bone marrow transplantation allowed

Chemotherapy:

• 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 50,000)
• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy allowed and recovered
• No concurrent radiotherapy

Surgery:

• Not specified