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

• ClinicalTrials.gov Identifier: NCT00129090
• Recruitment Status: Completed
• First Posted: August 11, 2005
• Last Update Posted: May 25, 2023
• Sponsor: German High-Grade Non-Hodgkin's Lymphoma Study Group
• Collaborator: Deutsche Krebshilfe e.V., Bonn (Germany)
• Information provided by (Responsible Party): Universität des Saarlandes ( German High-Grade Non-Hodgkin's Lymphoma Study Group )

Tracking Information

• First Submitted Date: August 10, 2005
• First Posted Date: August 11, 2005
• Last Update Posted Date: May 25, 2023
• Study Start Date: March 2003
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 8, 2015)

time to treatment failure [ Time Frame: 3 years after study inclusion ]

At 3 year follow up rate of treatments and time to treatment failure will be determined

• Original Primary Outcome Measures (submitted: August 10, 2005): time to treatment failure
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Mega-CHOEP: Conventional Chemo Vs HD Chemo Followed by Auto SCT in Younger Pts With Aggressive Non-Hodgkin's Lymphoma
• Official Title: 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
• Brief Summary: 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)

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
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Hodgkin's Lymphoma (NHL)

Intervention

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 Name: 12 x Rituximab with 8 cycles of standard CHOEP-14

Study Arms

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 )

Intervention: Drug: R-CHOEP 14 with 12x Rituximab

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 8, 2015): 450
• Original Enrollment (submitted: August 10, 2005): 396
• Actual Study Completion Date: October 2017
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT00129090
• Other Study ID Numbers: DSHNHL 2002-1
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Universität des Saarlandes ( German High-Grade Non-Hodgkin's Lymphoma Study Group )
• Original Responsible Party: Not Provided
• Current Study Sponsor: German High-Grade Non-Hodgkin's Lymphoma Study Group
• Original Study Sponsor: Same as current
• Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany)

Investigators

• Principal Investigator: Norbert Schmitz, Prof.; German High-Grade Non-Hodgkin's Lymphoma Study Group

• PRS Account: Universität des Saarlandes
• Verification Date: May 2023