RATIONALE: Drugs used in chemotherapy 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: Phase I trial to study the effect of combination chemotherapy on the body when treating patients who have relapsed or refractory aggressive non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the maximum tolerated dose and recommended dose of pixantrone when administered with cytarabine, methylprednisolone, and cisplatin in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
• Determine the dose-limiting toxic effects of this regimen in these patients.
• Determine the relationship between toxicity and systemic exposure to this regimen in these patients.
• Determine the safety of this regimen in these patients.
• Assess the pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of pixantrone.

Patients receive pixantrone IV over 1 hour on day 1, methylprednisolone IV over 15 minutes on days 1-5, cisplatin IV over 30 minutes on days 1-4, and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for at least 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of pixantrone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the recommended dose, which is defined as the dose preceding the MTD.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

• Drug: cisplatin
• Drug: cytarabine
• Drug: methylprednisolone
• Drug: pixantrone dimaleate

DISEASE CHARACTERISTICS:

• Histologically confirmed relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) including the following:

  • Diffuse large B-cell lymphoma
  • Transformed NHL
  • Follicular large cell lymphoma
  • Peripheral T-cell lymphoma
  • Unclassified aggressive histology (immunoblastic lymphoma)
• Must have received 1 to 3 prior chemotherapy treatment regimens (may include doxorubicin up to a cumulative dose of no greater than 450 mg/m^2)
• No Burkitt's lymphoma, lymphoblastic lymphoma, or mantle cell lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 to 64

Performance status

• WHO 0-1

Life expectancy

• At least 3 months

Hematopoietic

• Neutrophil count at least 1,500/mm^3*
• Platelet count at least 100,000/mm^3* NOTE: *Lower values may be accepted if evidence of bone marrow involvement

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)**
• Alkaline phosphatase no greater than 2 times ULN**
• AST or ALT no greater than 2 times ULN**
• No history or clinical symptoms of hepatitis B or C virus NOTE: **Higher values may be accepted if evidence of liver involvement

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• LVEF at least 50% by MUGA
• No clinically significant cardiovascular abnormalities
• No New York Heart Association class II-IV heart disease
• No myocardial infarction within the past 6 months
• No severe arrhythmia
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study
• No history or clinical symptoms of HIV
• No clinically significant neurological abnormalities
• No serious uncontrolled infection (NCI CTC grade 3-4)
• No condition that would place the patient at undue risk or interfere with the study results

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 months since prior radioimmunotherapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• At least 1 year since prior platinum or cytarabine (unless complete response to treatment)
• At least 2 years since prior fludarabine or nitrosoureas
• No prior cumulative cisplatin greater than 600 mg/m^2

Endocrine therapy

• Not specified

Radiotherapy

• See Biologic therapy
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to the whole pelvis

Surgery

• At least 1 week since prior minor surgery and recovered
• At least 4 weeks since prior major thoracic and/or abdominal surgery and recovered

Other

• At least 1 month since prior investigational drugs
• Recovered from prior therapy
• No other concurrent investigational drugs