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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Non-Hodgkin's Lymphoma (NHL)

Intervention / Treatment
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* Drug: R-CHOEP 14 with 12x Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-CHOEP14 with 12x Rituximab<br>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<br>* 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)<br>* Other names: 12 x Rituximab with 8 cycles of standard CHOEP-14;|

What is the study measuring?
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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 |