Trial Information

Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas

OBJECTIVES:

Primary

- Compare the event-free survival of patients with previously untreated de novo diffuse
large B-cell non-Hodgkin's lymphoma treated with R-CHOP comprising rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone vs EPOCH-R comprising
etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.

- Determine molecular predictors of outcome (using molecular profiling) in patients
treated with these regimens.

Secondary

- Compare the response rate and overall survival of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Correlate the clinical parameters (i.e., toxicity, response, survival outcomes, and
laboratory results) with molecular profiling in patients treated with these regimens.

- Assess the use of molecular profiling for pathological diagnosis in patients treated
with these regimens.

- Identify new therapeutic targets using molecular profiling.

- Perform a comprehensive analysis of somatic alterations to the tumor genome in order to
understand which genomic alterations are somatically acquired by the tumor and which
are encoded in the germ line of the patient.

- Identify biomarkers of response to chemotherapy by FDG-PET/CT imaging that are
predictive of histopathologic remissions and survival in patients with stage I
(mediastinal), II, III, or IV untreated DLBCL.

- Evaluate the use of semiquantitative measurements of FDG uptake in defining
FDG-PET/CT-based biomarkers of response to chemotherapy in patients with DLBCL.

- Determine whether FDG-PET/CT measurements of tumor response after the second cycle of
chemotherapy can predict clinical response.

- Establish a standardized protocol for FDG-PET/CT image acquisition.

- Determine additional FDG-PET/CT parameters (e.g., the ratio of tumor SUVmax to liver
SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine
physician's assessment) and evaluate their utility in refining FDG-PET/CT based
biomarkers of response to therapy.

- Evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this
indication.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms.

- Arm I (R-CHOP): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin IV over
3-5 minutes, and vincristine IV on day 1 and oral prednisone once daily on days 1-5.
Treatment repeats every 21 days for 6 courses in the absence of disease progression or
unacceptable toxicity.

- Arm II (EPOCH-R): Patients receive rituximab IV on day 1, doxorubicin IV, etoposide IV,
and vincristine IV continuously over 96 hours on days 1-4, cyclophosphamide IV on day
5, and oral prednisone twice daily on days 1-5. Patients also receive filgrastim
(G-CSF) once daily on days 2-11 or until blood counts recover. Treatment repeats every
21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

As of July 1, 2012, the FDG-PET/CT imaging companion study CALGB-580603 will be required of
all patients enrolling on this study. FDG-PET/CT scans of abdomen/chest/pelvis are collected
at baseline, post-course 2, and post-course 6.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 478 patients (239 per treatment arm) will be accrued for this
study within 4.5 years.