Mega-CHOEP: Conventional Chemo Vs HD Chemo Followed by Auto SCT in Younger Pts With Aggressive Non-Hodgkin's Lymphoma

A Randomized Phase III Study to Compare Conventional Chemotherapy (CHOEP-14) + Rituximab vs High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation (Mega-CHOEP-21) + Rituximab in Younger Patients With Aggressive NHL

According to amendment 3 this study addresses the question if intensification of administration of rituximab in standard treatment for patients with newly diagnosed aggressive B-Non Hodgkin Lymphoma (B-NHL) and high risk (aaIPI 2 or 3) results in a better time to treatment failure (TTTF)

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma (NHL)
• Intervention / Treatment: Drug: R-CHOEP 14 with 12x Rituximab

Detailed Description

This study was primarily designed to compare aggressive conventional chemotherapy with a repetitive high-dose (HD) therapy program using identical, effective drugs at highest possible dose and dose intensity with/without addition of rituximab (initially 4 treatment arms). In 2004 the first amendment had to be added in order to close two treatment arms without rituximab due to recent data revealing a significant advantage for rituximab-treated patients with CD20+lymphoma.

A planned interim analysis in 2010 revealed inferiority of the high-dose treatment thus in the 2nd amendment the high-dose arm was closed and additionally the rituximab frequency was raised from 6 to 12 administrations as recent publications gave hint for advantage. The last amendment was added in 2010 to adjust for delayed recruitment mainly due to organisation problems.

As the high-dose arm was closed only CD20+ B-lymphoma were included past amendment 2.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20099
    • AK St. Georg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-60 years of age
• Risk group International Prognostic Index (IPI) 2 and 3 (age adjusted)
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-3
• Patient's written informed consent
• Aggressive non-Hodgkin's lymphoma with CD20+ histology

Exclusion Criteria:

• Already initiated lymphoma therapy
• Serious accompanying disorder or impaired organ function
• Bone marrow involvement > 25%
• Known hypersensibility to the medications to be used
• Known HIV-positivity
• Active hepatitis infection
• Suspicion that patient compliance will be poor
• Simultaneous participation in other trials
• Prior chemo- or radiotherapy for previous disorder
• Other concomitant tumour disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R-CHOEP14 with 12x Rituximab; 8 cycles of standard CHOP with etoposide in 14-day intervals. Patients with CD20+ lymphoma receive 12 doses of Rituximab (day 0,1,4,8 of cycle 1, day 1 and 8 of cycle 2, day1 of cycle 3-8 )	Drug: R-CHOEP 14 with 12x Rituximab; after amendment 3 patients receive 4x 375mg/m2 in cycle 1 (day 0,1,4,8), 2x 375/m2 in cycle 2 (day1,8) and 1x 375mg/m2 cycle 3-8 (day 1 of each cycle); Other Names: 12 x Rituximab with 8 cycles of standard CHOEP-14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to treatment failure	At 3 year follow up rate of treatments and time to treatment failure will be determined	3 years after study inclusion

Collaborators and Investigators

• Sponsor: German High-Grade Non-Hodgkin's Lymphoma Study Group
• Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany)
• Investigators: Principal Investigator: Norbert Schmitz, Prof., German High-Grade Non-Hodgkin's Lymphoma Study Group

Publications and helpful links

General Publications

• Frontzek F, Ziepert M, Nickelsen M, Altmann B, Glass B, Haenel M, Truemper L, Held G, Bentz M, Borchmann P, Dreyling M, Viardot A, Kroschinsky FP, Metzner B, Staiger AM, Horn H, Ott G, Rosenwald A, Loeffler M, Lenz G, Schmitz N. Rituximab plus high-dose chemotherapy (MegaCHOEP) or conventional chemotherapy (CHOEP-14) in young, high-risk patients with aggressive B-cell lymphoma: 10-year follow-up of a randomised, open-label, phase 3 trial. Lancet Haematol. 2021 Apr;8(4):e267-e277. doi: 10.1016/S2352-3026(21)00022-3. Epub 2021 Mar 2.
• Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-9. doi: 10.1016/S1470-2045(12)70481-3. Epub 2012 Nov 16.

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: August 10, 2005
• First Submitted That Met QC Criteria: August 10, 2005
• First Posted (Estimated): August 11, 2005

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: DSHNHL 2002-1