Trial Information

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]

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.