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

This study has been completed.
Sponsor:
Collaborators:
Ministry of Health, Czech Republic
Hoffmann-La Roche
Information provided by:
Czech Lymphoma Study Group
ClinicalTrials.gov Identifier:
NCT00558220
First received: February 12, 2007
Last updated: November 10, 2007
Last verified: November 2007
  Purpose

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.


Condition Intervention Phase
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 Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Czech Lymphoma Study Group:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 3 years ]

Secondary Outcome Measures:
  • Complete remission and overall response rate [ Time Frame: One year ]
  • Overall survival [ Time Frame: 3 years ]

Enrollment: 106
Study Start Date: May 2002
Study Completion Date: October 2006
Arms Assigned Interventions
Experimental: A
Intensive induction followed by high-dose consolidation with stem cell support ± radiotherapy
Procedure: immunotherapy

Given together with induction chemotherapy:

Rituximab - 375 mg/m2 iv every 3 weeks, 4-6 doses

Procedure: Induction treatment part 1

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 2 with PBPC collection

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: Induction treatment part 3

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.

Procedure: Consolidation treatment part 1: HD-chemotherapy with ASCT

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.

Radiation: Consolidation treatment part 2: Radiotherapy
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558220

Locations
Czech Republic
University Hospital Brno-Bohunice
Brno, Czech Republic, 625 00
Hospital Chomutov
Chomutov, Czech Republic, 430 12
University Hospital Hradec Králové
Hradec Králové, Czech Republic, 500 05
General University Hospital
Prague, Czech Republic, 128 08
University Hospital Motol
Prague, Czech Republic, 150 00
University Hospital Královské Vinohrady
Prague, Czech Republic, 100 34
Hospital Ústí nad Labem
Usti nad Labem, Czech Republic, 401 13
Hospital České Budějovice
České Budějovice, Czech Republic
Sponsors and Collaborators
Czech Lymphoma Study Group
Ministry of Health, Czech Republic
Hoffmann-La Roche
Investigators
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
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00558220     History of Changes
Other Study ID Numbers: CLSG 5_02, NR-8231/3
Study First Received: February 12, 2007
Last Updated: November 10, 2007
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by Czech Lymphoma Study Group:
Lymphoma, B-cell
Immunotherapy, passive
Remission induction
Autologous transplantation

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 23, 2014