Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Study Overview
=================
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.

Official Title
-----------------
A Phase I Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin in the Treatment of Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Drug: cisplatin
* Drug: cytarabine
* Drug: methylprednisolone
* Drug: pixantrone dimaleate


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: cytarabine|nan|
|Drug: methylprednisolone|nan|
|Drug: pixantrone dimaleate|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent adult diffuse large cell lymphoma, recurrent grade 3 follicular lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma