Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin's Lymphoma in First Relapse

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as pixantrone, cytarabine, methylprednisolone, and cisplatin, work in 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 II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed aggressive non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the antitumor activity of pixantrone, cytarabine, methylprednisolone, and cisplatin in patients with aggressive non-Hodgkin's lymphoma in first relapse. Determine the safety and tolerability of this regimen in these patients. Determine the validity and safety of this regimen as a mobilization regimen before high-dose chemotherapy with stem cell support in these patients. OUTLINE: This is an open-label, multicenter study. Salvage therapy: Patients receive pixantrone IV over 1 hour on day 1; cisplatin IV over 30 minutes on days 1-4; methylprednisolone IV over 15-30 minutes on days 1-5; and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After 2 courses of salvage therapy, patients are re-evaluated and treated as follows: Complete response (CR) or partial response (PR): Patients with a CR or PR who are suitable candidates for autologous stem cell transplantation (ASCT) proceed to mobilization therapy, high-dose chemotherapy, and ASCT. Patients with a CR or PR who are unsuitable candidates for ASCT continue to receive salvage therapy for up to 6 courses in the absence of disease progression or unacceptable toxicity. Stable disease: Patients with stable disease continue to receive salvage therapy for up to 6 courses. Patients who have a CR or PR after 3-4 courses of salvage therapy and who are suitable candidates for ASCT proceed to mobilization therapy, high-dose chemotherapy, and ASCT off study at the investigator's discretion. Mobilization therapy (optional regimen; regimen used for mobilization is at the investigator's discretion): Patients receive rituximab* IV on days 1 and 7; pixantrone IV over 1 hour on day 2; cisplatin IV over 30 minutes on days 2-5; cytarabine IV over 2 hours on day 6; and methylprednisolone IV over 15-30 minutes on days 2-6. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 7 and continuing until blood counts recover. Patients receive 1 or more courses of mobilization therapy during which stem cells are harvested. Patients then proceed to high-dose chemotherapy and subsequent re-infusion of harvested stem cells. NOTE: *If this mobilization regimen is used, patients with T-cell lymphoma do not receive rituximab High-dose chemotherapy and ASCT: Patients receive high-dose chemotherapy and ASCT per institutional standard practice. Patients are followed every 3 months for 2 years. PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Official Title
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A Phase II Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin (BSHAP) as Salvage in Patients With Relapsed Aggressive Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: rituximab
* Drug: cisplatin
* Drug: cytarabine
* Drug: methylprednisolone
* Drug: pixantrone dimaleate
* Procedure: autologous bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) Any stage, with or without B symptoms The following subtypes are eligible: Diffuse large cell (B and T cell types) Anaplastic large cell Diffuse mixed cell Immunoblastic large cell Follicular large cell Transformed follicular NHL Diffuse aggressive not otherwise classified Burkitt-like lymphoma Bone marrow positive or negative At least 1 measurable lesion Patients with bone marrow as the only site of disease are eligible without a measurable lesion No more than 1 episode of progressive disease, occurring after a response (complete response [CR], complete response unconfirmed [CR_u], or partial response [PR]) to prior chemotherapy* NOTE: *Patients with less than a CR, CRu, or PR and no progression, but who are good candidates for high-dose chemotherapy with stem cell support may be eligible (will be decided on an individual basis) No chemotherapy-refractory disease, defined as follows: Stable or progressive disease documented at restaging immediately after the completion of induction therapy No lymphoblastic lymphoma, or mantle cell lymphoma PATIENT CHARACTERISTICS: Age 18 and over 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 clearly due to bone marrow involvement by lymphoma Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN)* AST or ALT no greater than 2.0 times ULN* Alkaline phosphatase no greater than 2.0 times ULN* No history or clinical symptoms of hepatitis B or hepatitis C virus Patients with seropositivity due to prior vaccination for hepatitis B are eligible NOTE: *Higher values may be accepted if clearly due to liver involvement by lymphoma 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 grade II-IV cardiovascular disease No myocardial infarction within the past 6 months No severe cardiac arrhythmia No uncontrolled hypertension Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study participation HIV negative No clinically significant neurological abnormalities No condition that would preclude study safety or interfere with study results No concurrent serious uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy Prior rituximab immediately after the first chemotherapy regimen allowed Chemotherapy See Disease Characteristics See Biologic therapy At least 6 months since prior anthracycline therapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) More than 2 years since prior fludarabine More than 2 years since prior nitrosoureas More than 1 year since prior platinum-based chemotherapy or cytarabine, unless a CR or CR_u was achieved No prior cumulative dose of cisplatin greater than 600 mg/m^2 No prior single or cumulative dose of doxorubicin greater than 450 mg/m^2 Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the whole pelvis No prior radioimmunotherapy Surgery More than 4 weeks since prior major thoracic and/or abdominal surgery At least 1 week since prior minor surgery Other Recovered from prior therapy Alopecia allowed Grade 1 peripheral neuropathy allowed More than 30 days since prior participation in another investigational drug study No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Biological: rituximab|nan|
|Drug: cisplatin|nan|
|Drug: cytarabine|nan|
|Drug: methylprednisolone|nan|
|Drug: pixantrone dimaleate|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult diffuse large cell lymphoma, anaplastic large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult Burkitt lymphoma