Lymphoma
Conditions
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
Brief 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.
Detailed description
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.
Interventions
Sponsors
Theradex
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed