DX-8951f in Treating Children With Advanced Solid Tumors or Lymphomas

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of DX-8951f in treating children who have advanced solid tumors or lymphomas that have not responded to previous therapy.

OBJECTIVES:

* Determine the maximum tolerated dose of exatecan mesylate (DX-8951f) with and without filgrastim (G-CSF) in pediatric patients with advanced solid tumors or lymphomas.
* Determine the toxic effects, including dose-limiting toxicity, of exatecan mesylate in these patients.
* Determine the pharmacokinetics of exatecan mesylate in these patients.
* Determine the recommended dose of exatecan mesylate for phase II study.
* Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of exatecan mesylate (DX-8951f). Patients are stratified according to prior treatment (minimally treated vs heavily treated).

Patients receive exatecan mesylate IV over 30 minutes daily for 5 days. Patients in dose levels 5 and above also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing for at least 7 days or until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of exatecan mesylate with and without G-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed advanced solid tumors, including brain tumors and lymphomas, that have failed standard therapy (surgery, radiotherapy, endocrine therapy, or chemotherapy) or for which no standard therapy exists

  * Histology requirement waived for brain stem gliomas

PATIENT CHARACTERISTICS:

Age:

* 21 and under at diagnosis

Performance status:

* ECOG 0-2

Life expectancy:

* At least 8 weeks

Hematopoietic:

* Absolute neutrophil count at least 750/mm\^3
* Platelet count at least 75,000/mm\^3
* Hemoglobin at least 8.5 g/dL

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* SGOT or SGPT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases)

Renal:

* Creatinine no greater than 1.5 times ULN OR
* GFR at least 70 mL/min

Other:

* Not pregnant or nursing
* Negative pregnancy test
* No history of severe or life-threatening hypersensitivity to camptothecin analogs
* HIV negative
* No other concurrent severe or uncontrolled medical illness
* No systemic infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Recovered from prior immunotherapy

Chemotherapy:

* See Disease Characteristics
* Recovered from prior chemotherapy

Endocrine therapy:

* See Disease Characteristics

Radiotherapy:

* See Disease Characteristics
* At least 4 weeks since prior extensive radiotherapy involving cranial, whole pelvic, or at least 25% of bone marrow reserve
* Recovered from prior radiotherapy
* Concurrent localized radiotherapy for pain allowed

Surgery:

* See Disease Characteristics
* Recovered from prior surgery

Other:

* No other concurrent antitumor therapy
* No concurrent drugs that induce or inhibit CYP3A enzyme