NCT00278408|CompletedPhase 3Results

Rituximab and Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

Randomized Study Comparing an Immuno-Chemotherapy With 6 Cycles of the Monoclonal Anti-CD20 Antibody Rituximab in Combination With 6 Cycles of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) at 21-day Intervals or 14-day Intervals, Both With or Without Consolidating Radiotherapy or Large Tumour Masses (≥7.5 cm) and/or Extranodal Involvement in Patients With Aggressive CD20 B-Cell Lymphoma Aged 18 to 60 Years With Age-Adjusted IPI=1 (All) or IPI=0 With a Large Tumour Mass (≥7.5 cm) [UNFOLDER 21/14 Study]

German High-Grade Non-Hodgkin's Lymphoma Study Group ClinicalTrials.gov

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4 other identifiers

CDR0000459796DSHNHL-2004-3EUDRACT-2005-005218-19EU-205111

Study Type

interventional

Target

700

Locations

4 countries

Sites

152

Timeline

RegisteredJan 2006

StartedJan 2006

CompletionFeb 2018

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving rituximab and combination chemotherapy together with radiation therapy may kill more cancer cells. It is not yet known which schedule of rituximab and combination chemotherapy is more effective when given with or without radiation therapy in treating non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy with or without radiation therapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

700

participants targeted

Target at P75+ for phase_3 lymphoma

Timeline

Completed

Started Jan 2006

Longer than P75 for phase_3 lymphoma

Geographic Reach

4 countries

152 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

12.1 years study duration

Study Start

First participant enrolled

January 2, 2006

Completed

14 days until next milestone

First Submitted

Initial submission to the registry

January 16, 2006

Completed

2 days until next milestone

First Posted

Study publicly available on registry

January 18, 2006

Completed

12 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2018

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2018

Completed

7.6 years until next milestone

Results Posted

Study results publicly available

August 26, 2025

Completed

Last Updated

August 26, 2025

Status Verified

May 1, 2025

Enrollment Period

12.1 years

First QC Date

January 16, 2006

Results QC Date

July 2, 2021

Last Update Submit

August 7, 2025

Conditions

Lymphoma

Keywords

contiguous stage II grade 3 follicular lymphomanoncontiguous stage II grade 3 follicular lymphomastage I grade 3 follicular lymphomastage III grade 3 follicular lymphomastage IV grade 3 follicular lymphomacontiguous stage II adult diffuse large cell lymphomacontiguous stage II adult diffuse mixed cell lymphomanoncontiguous stage II adult diffuse large cell lymphomanoncontiguous stage II adult diffuse mixed cell lymphomastage I adult diffuse large cell lymphomastage I adult diffuse mixed cell lymphomastage III adult diffuse large cell lymphomastage III adult diffuse mixed cell lymphomastage IV adult diffuse large cell lymphomastage IV adult diffuse mixed cell lymphomanodal marginal zone B-cell lymphomaanaplastic large cell lymphomacontiguous stage II adult immunoblastic large cell lymphomanoncontiguous stage II adult immunoblastic large cell lymphomastage I adult immunoblastic large cell lymphomastage III adult immunoblastic large cell lymphomastage IV adult immunoblastic large cell lymphomacontiguous stage II adult Burkitt lymphomacontiguous stage II mantle cell lymphomanoncontiguous stage II adult Burkitt lymphomanoncontiguous stage II mantle cell lymphomastage I adult Burkitt lymphomastage I mantle cell lymphomastage III adult Burkitt lymphomastage III mantle cell lymphomastage IV adult Burkitt lymphomastage IV mantle cell lymphomacontiguous stage II marginal zone lymphomanoncontiguous stage II marginal zone lymphomastage I marginal zone lymphomastage III marginal zone lymphomastage IV marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

3 Years Event-free Survival
Event-free survival was the primary endpoint, which was defined as the time from randomization until one of the following events had occurred: progression during therapy, partial response, no change, unknown status at the end of study therapy, relapse after complete response or unconfirmed complete response, death from any cause; or additional treatment, whichever came first.
Each patient will be observed for 3 years starting from completion of treatment.

Secondary Outcomes (9)

3 Years Progression-free Survival
Each patient will be observed for 3 years starting from completion of treatment.
3 Years Overall Survival
Each patient will be observed for 3 years starting from completion of treatment.
Rate of Complete Remissions and Progressive Disease
Each patient will be observed for 3 years starting from completion of treatment.
Number of Patients With a Relapse After a CR/CRu
Each patient will be observed for 3 years starting from completion of treatment.
Safety (Adverse Events, Serious Adverse Events, Rate of Secondary Neoplasia, Selected Laboratory Parameters, Including Leucocytes, Thrombocytes, and Haemoglobin)
Each patient will be observed for 3 years starting from completion of treatment.
+4 more secondary outcomes

Study Arms (4)

Interventional: 6 R-CHOP-21

ACTIVE COMPARATOR

Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: rituximabDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: prednisoneDrug: vincristine sulfate

Interventional: 6 R-CHOP-21 + radiotherapy

ACTIVE COMPARATOR

Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.

Biological: rituximabDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: prednisoneDrug: vincristine sulfateRadiation: radiation therapy

Interventional: 6 R-CHOP-14

ACTIVE COMPARATOR

Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: filgrastimBiological: rituximabDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: prednisoneDrug: vincristine sulfate

Interventional: 6 R-CHOP-14 and radiotherapy

ACTIVE COMPARATOR

Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.

Biological: filgrastimBiological: rituximabDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: prednisoneDrug: vincristine sulfateRadiation: radiation therapy