R-MegaCHOP-ESHAP-BEAM in Patients With High-Risk Aggressive B-Cell Lymphomas (R-MCEB)
|Diffuse Large B-Cell Lymphoma. Primary Mediastinal B-Cell Lymphoma Follicular Lymphoma Grade III||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||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Intensive Induction (R-MegaCHOP/ESHAP)Followed By Intensive Consolidation (BEAM) In Treatment Of High-Risk Aggressive B-Cell Lymphomas|
- Progression-free survival [ Time Frame: 3 years ]
- Complete remission and overall response rate [ Time Frame: One year ]
- Overall survival [ Time Frame: 3 years ]
|Study Start Date:||May 2002|
|Study Completion Date:||October 2006|
Intensive induction followed by high-dose consolidation with stem cell support ± radiotherapy
Procedure: Induction treatment part 1
Given together with induction chemotherapy:
Rituximab - 375 mg/m2 iv every 3 weeks, 4-6 doses
Procedure: Induction treatment part 2 with PBPC collection
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.
Procedure: Induction treatment part 3
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.
Procedure: Consolidation treatment part 1: HD-chemotherapy with ASCT
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.
Radiation: Consolidation treatment part 2: Radiotherapy
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00558220
|University Hospital Brno-Bohunice|
|Brno, Czech Republic, 625 00|
|Chomutov, Czech Republic, 430 12|
|University Hospital Hradec Králové|
|Hradec Králové, Czech Republic, 500 05|
|University Hospital Královské Vinohrady|
|Prague, Czech Republic, 100 34|
|General University Hospital|
|Prague, Czech Republic, 128 08|
|University Hospital Motol|
|Prague, Czech Republic, 150 00|
|Hospital Ústí nad Labem|
|Usti nad Labem, Czech Republic, 401 13|
|Hospital České Budějovice|
|České Budějovice, Czech Republic|
|Principal Investigator:||Pytlik Robert, M.D.||1st Department of Medicine, General University Hospital, Prague|
|Study Director:||Marek Trněný, M.D., PhD.||General University Hospital, Prague|