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

November 10, 2007 updated by: Czech Lymphoma Study Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

106

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czech Republic
      • Brno, Czech Republic, 625 00
        • University Hospital Brno-Bohunice
      • Chomutov, Czech Republic, 430 12
        • Hospital Chomutov
      • Hradec Králové, Czech Republic, 500 05
        • University Hospital Hradec Kralove
      • Prague, Czech Republic, 100 34
        • University Hospital Kralovske Vinohrady
      • Prague, Czech Republic, 128 08
        • General University Hospital
      • Prague, Czech Republic, 150 00
        • University Hospital Motol
      • Usti nad Labem, Czech Republic, 401 13
        • Hospital Usti nad Labem
      • České Budějovice, Czech Republic
        • Hospital České Budějovice

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 3 years
3 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Czech Lymphoma Study Group

Collaborators

Hoffmann-La Roche
Ministry of Health, Czech Republic

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Study Completion (Actual)

October 1, 2006

Study Registration Dates

First Submitted

February 12, 2007

First Submitted That Met QC Criteria

November 10, 2007

First Posted (Estimate)

November 14, 2007

Study Record Updates

Last Update Posted (Estimate)

November 14, 2007

Last Update Submitted That Met QC Criteria

November 10, 2007

Last Verified

November 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLSG 5_02
  • NR-8231/3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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