combination chemotherapy in treating patients with relapsed or refractory aggressive non-hodgkin's lymphoma

Conditions: Lymphoma

Summary: 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.

Eligibility criteria:
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

Keywords: recurrent adult diffuse large cell lymphoma recurrent grade 3 follicular lymphoma recurrent cutaneous t-cell non-hodgkin lymphoma recurrent adult immunoblastic large cell lymphoma