R-MegaCHOP-ESHAP-BEAM in Patients With High-Risk Aggressive B-Cell Lymphomas

Study Overview
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Brief Summary
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The purpose of this study is to show if addition of Rituximab to intensive induction (MegaCHOP/ESHAP) and high-dose consolidation (BEAM) improves progression-free and overall survival in patients younger than 65 years with aggressive B-cell lymphoma and aaIPI 2 or 3.

Detailed Description
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Previous study of Czech Lymphoma Study Group (4_2002)have shown that intensive induction (MegaCHOP - Cyclophosphamide 3 g/m2, Vincristine 2 mg, Adriamycin 75 mg/m2, Prednisone 300 mg/m2 every three weeks with G-CSF for three cycles, followed by ESHAP - Etoposide 240 mg/m2, Cisplatin 100 mg/m2, Solumedrol 2000 mg and cytarabine 2000 mg/m2 for three cycles every three weeks with G-CSF) followed by intensive consolidation (BEAM) and stem cell support improves progression-free survival in adult patients (18-65 years old) with aggressive B-cell lymphoma (namely, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and follicular lymphoma grade II) with aaIPI 2 and namely, with aaIPI 3. This study was aimed to find out if addition of four to six doses of Rituximab 375 mg/m2 on first day of every cycle of intensive induction further improves prognosis of these patients. Inclusion criteria for this trial were: newly diagnosed aggressive B-cell lymphoma, namely diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and follicular lymphoma grade III age 18-65 years age adjusted IPI (International Prognostic Index) score 2 or 3 ECOG performance status 0-3 signed informed consent Exclusion criteria were: relapsed lymphoma previous treatment (up to one cycle of standard pretreatment - COP, CHOP or steroids was permitted and later became mandatory to decrease disease burden and/or improve the performance status of the patient) Burkitt lymphoma posttransplant lymphoproliferation CNS involvement other malignant tumor in previous history, except basalioma, skin squamocellular carcinoma or cervical carcinoma in situ other serious comorbidity Primary endpoints was progression-free survival Secondary endpoints were: rate of complete remission and overall response rate overall survival toxicity of the protocol, measured as grade III-IV toxicity and/or inability to finish the protocol as planned Planned number of accrued patients was 100.

Official Title
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Phase II Study of Intensive Induction (R-MegaCHOP/ESHAP)Followed By Intensive Consolidation (BEAM) In Treatment Of High-Risk Aggressive B-Cell Lymphomas

Conditions
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Diffuse Large B-Cell Lymphoma., Primary Mediastinal B-Cell Lymphoma, Follicular Lymphoma Grade III

Intervention / Treatment
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* Procedure: immunotherapy
* Procedure: Induction treatment part 1
* Procedure: Induction treatment part 2 with PBPC collection
* Procedure: Induction treatment part 3
* Procedure: Consolidation treatment part 1: HD-chemotherapy with ASCT
* Radiation: Consolidation treatment part 2: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aggressive B-cell lymphoma, namely diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma grade III Age 18-65 years Age-adjusted IPI score 2-3 ECOG performance status 0-3 Signed informed consent Exclusion Criteria: Burkitt lymphoma Posttransplant lymphoproliferation Previous treatment (up to one cycle of standard pretreatment with COP, CHOP or steroids permitted and latter mandatory to decrease tumor burden and/or improve performance status) Other tumor in previous history with the exception of basalioma, squamous cell carcinoma of the skin or cervical carcinoma in situ Pregnancy/lactation CNS involvement Other serious comorbidities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Intensive induction followed by high-dose consolidation with stem cell support ± radiotherapy | Procedure: immunotherapy<br>* Given together with induction chemotherapy: Rituximab - 375 mg/m2 iv every 3 weeks, 4-6 doses<br>Procedure: Induction treatment part 1<br>* cyclophosphamide 3000 mg/m2 iv every 3 weeks, 3 cycles vincristin 2 mg iv every 3 weeks, 3 cycles doxorubicin 75 mg/m2 iv every 3 weeks, 3 cycles Prednisolone 300 mg/m2 divided into five days po every 3 weeks, 3 cycles pegfilgrastim 6 mg sc every 3 weeks. 3 cycles consisting of combination treatment of above mentioned drugs are given.<br>Procedure: Induction treatment part 2 with PBPC collection<br>* Starts three weeks after last cycle of Induction part 1. Etoposide 240 mg/m2 divided into equal doses for four days, together with methylprednisolone 2000 mg divided into equal doses for four days, together with cisplatin 100 mg/m2 divided into equal doses for four days, and together with cytarabine 2000 mg/m2 iv one dose on 4th day of treatment. Filgrastim 10-12 ug/kg from day five after start of chemotherapy untill stem cell collection. Peripheral blood progenitor cell collection (PBPC) is started when CD34 positive cells are >20/cubic milimeter of blood and continued untill 5 million of CD34 positive cells are collected from peripheral blood.<br>Procedure: Induction treatment part 3<br>* Part 3 of induction treatment is given approximately one week after the end of Part 2. Etoposide 240 mg/m2 divided into equal doses for four days, methylprednisolone 2000 mg divided into equal doses for four days, cisplatin 100 mg/m2 divided into equal doses for four days, cytarabine 2000 mg/m2 iv one dose on day 4 of chemotherapy and pegfilgrastim 6 mg on day five of chemotherapy are given twice three weeks apart.<br>Procedure: Consolidation treatment part 1: HD-chemotherapy with ASCT<br>* Consolidation treatment Part 1 starts 4-8 weeks after the second cycle of Induction treatment Part 3. High dose chemotherapy (HD-chemotherapy) consists of: BCNU 300 mg/m2 is given on day 1, etoposide 800 mg/m2 divided into four equal doses is given on day 2-5, cytarabine 1600 mg/m2 divided into eight equal doses is given on day 2-5, melphalan 140 mg/m2 is given on day 6. On day 7, collected stem cells from peripheral blood (see Induction treatment part 1) are infused back to the patient. This is called autologous transplantation (ASCT). Filgrastim 5 ug/kg is given from day 14 (start of the chemotherapy being day 1) until neutrophil recovery.<br>Radiation: Consolidation treatment part 2: Radiotherapy<br>* Radiotherapy is started given 4-8 weeks after the autologous transplantation. It is given to patients with initially bulky disease (>10 cm at diagnosis) or to patients with residual disease after Induction treatment part 1-3 and Consolidation treatment part 1. 30-40 Gy are given in 2 Gy fractions over 3-4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission and overall response rate |  | One year | 
| Overall survival |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, B-cell, Immunotherapy, passive, Remission induction, Autologous transplantation