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

Registration Number
NCT00278408
Lead Sponsor
German High-Grade Non-Hodgkin's Lymphoma Study Group
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.

Detailed Description

OBJECTIVES:

Primary

* Compare the time to treatment failure in patients with previously untreated, low-risk, aggressive, B-cell non-Hodgkin's lymphoma treated with 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone with vs without radiotherapy.

Secondary

* Compare the time to progression in patients treated with these regimens.

* Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.

* Compare the complete response rate in patients treated with these regimens.

* Compare the tumor control in patients treated with these regimens.

* Compare the safety of these regimens in these patients.

* Compare the pharmacoeconomics of these regimens.

* Compare patient adherence to these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to study center, serum lactic dehydrogenase level (≤ upper limit of normal \[ULN\] vs \> ULN), disease stage (I or II vs III or IV), ECOG performance status (0-1 vs 2-3), bulky disease, and extranodal involvement. Patients with initial bulky disease and/or qualifying extranodal involvement are randomized to 1 of 4 treatment arms. Patients with non-bulky disease are randomized to treatment arms I or III.

All patients will be given the option of receiving a 1-week course of pretreatment therapy comprising vincristine IV once on day -6 and oral prednisone once daily on days -6 to 0.

* 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.

* 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.

* 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.

* 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.

Patients in all arms undergo restaging of their disease after courses 3 and 6 of R-CHOP. Patients with stable disease after 6 courses or disease progression after courses 3 or 6 proceed to salvage chemotherapy off study. Patients achieving a partial remission or an unconfirmed CR after 6 courses undergo additional restaging 4 weeks later. Patients with disease progression proceed to salvage chemotherapy off study. Patients who achieve CR after 6 courses of R-CHOP or have a confirmed CR after the additional restaging undergo radiotherapy according to randomization (as above).

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,072 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
700
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Interventional: 6 R-CHOP-21vincristine sulfateArm 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.
Interventional: 6 R-CHOP-21 + radiotherapyvincristine sulfateArm 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.
Interventional: 6 R-CHOP-21 + radiotherapyradiation therapyArm 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.
Interventional: 6 R-CHOP-14vincristine sulfateArm 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.
Interventional: 6 R-CHOP-14 and radiotherapyvincristine sulfateArm 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.
Interventional: 6 R-CHOP-14 and radiotherapyradiation therapyArm 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.
Interventional: 6 R-CHOP-21rituximabArm 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.
Interventional: 6 R-CHOP-14 and radiotherapyfilgrastimArm 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.
Interventional: 6 R-CHOP-21 + radiotherapyrituximabArm 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.
Interventional: 6 R-CHOP-14 and radiotherapyrituximabArm 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.
Interventional: 6 R-CHOP-14rituximabArm 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.
Interventional: 6 R-CHOP-14filgrastimArm 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.
Interventional: 6 R-CHOP-21cyclophosphamideArm 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.
Interventional: 6 R-CHOP-21doxorubicin hydrochlorideArm 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.
Interventional: 6 R-CHOP-21 + radiotherapycyclophosphamideArm 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.
Interventional: 6 R-CHOP-21prednisoneArm 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.
Interventional: 6 R-CHOP-21 + radiotherapydoxorubicin hydrochlorideArm 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.
Interventional: 6 R-CHOP-21 + radiotherapyprednisoneArm 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.
Interventional: 6 R-CHOP-14cyclophosphamideArm 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.
Interventional: 6 R-CHOP-14doxorubicin hydrochlorideArm 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.
Interventional: 6 R-CHOP-14prednisoneArm 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.
Interventional: 6 R-CHOP-14 and radiotherapycyclophosphamideArm 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.
Interventional: 6 R-CHOP-14 and radiotherapydoxorubicin hydrochlorideArm 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.
Interventional: 6 R-CHOP-14 and radiotherapyprednisoneArm 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.
Primary Outcome Measures
NameTimeMethod
3 Years Event-free SurvivalEach patient will be observed for 3 years starting from completion of treatment.

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.

Secondary Outcome Measures
NameTimeMethod
3 Years Progression-free SurvivalEach patient will be observed for 3 years starting from completion of treatment.

Progression of disease is defined as: recurrence of disease symptoms, development of new lymphatic or extralymphatic lesions or marked increase in lymphoma manifestation size by more than 25% in comparison with baseline.

3 Years Overall SurvivalEach patient will be observed for 3 years starting from completion of treatment.

Overall survival was defined as the time from randomization to death of any cause.

Rate of Complete Remissions and Progressive DiseaseEach patient will be observed for 3 years starting from completion of treatment.
Number of Patients With a Relapse After a CR/CRuEach patient will be observed for 3 years starting from completion of treatment.

Relapse is defined as, recurrence of disease symptoms, development of new lymphatic or extralymphatic lesions or a marked increase in lymphoma manifestation size by more thyn 25% after at least 2 months CR or CRu from the time point of the final restaging examination

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.
Adherence to Protocol - Absolute Dose Vincristine and Prednisone in mg (Median)Each patient will be observed for 3 years starting from completion of treatment.
Health-economic Aspects - Number of Patients Who Received Antibiotic Intervention and/or Red Blood Cell and Platelet TransfusionEach patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Total Duration of Chemotherapy in Days (Median)Each patient will be observed for 3 years starting from completion of treatment.
Adherence to Protocol - Absolute Dose Cyclophosphamide, Doxorubicin and Rituximab in mg/m² (Median)Each patient will be observed for 3 years starting from completion of treatment.

Trial Locations

Locations (152)

Rigshospitalet, Department of Hematology

🇩🇰

Copenhagen, Denmark

Amtssygehuset i Herlev

🇩🇰

Herlev, Denmark

GMP Tummes/Weinberg

🇩🇪

Aachen, Germany

Klinikum St. Marien

🇩🇪

Amberg, Germany

Klinikum Augsburg

🇩🇪

Augsburg, Germany

Kreiskrankenhaus Aurich

🇩🇪

Aurich, Germany

Klinikum Bayreuth

🇩🇪

Bayreuth, Germany

Charite - Campus Charite Mitte

🇩🇪

Berlin, Germany

Charite University Hospital - Campus Virchow Klinikum

🇩🇪

Berlin, Germany

Helios Klinikum Berlin-Buch, Department of Hematology and Stem Cell Transplantation

🇩🇪

Berlin, Germany

Scroll for more (142 remaining)
Rigshospitalet, Department of Hematology
🇩🇰Copenhagen, Denmark

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