Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma
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|ClinicalTrials.gov Identifier: NCT00118209|
Recruitment Status : Completed
First Posted : July 11, 2005
Results First Posted : April 17, 2020
Last Update Posted : November 17, 2021
This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.
|Condition or disease||Intervention/treatment||Phase|
|Large B Cell Lymphoma||Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin Drug: vincristine Drug: prednisone Drug: etoposide Drug: filgrastim Drug: pegfilgrastim||Phase 3|
I. To compare the event-free survival of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP) versus dose-adjusted (DA-) etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, and rituximab (EPOCH-R) chemotherapy in untreated cluster of differentiation (CD)20 positive (+) diffuse large B-cell lymphomas.
II. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling.
I. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R.
II. To define the pharmacogenomics of untreated diffuse large B-cell lymphoma (DLBCL) and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling.
III. To assess the use of molecular profiling for pathological diagnosis. IV. To identify new therapeutic targets using molecular profiling. V. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.
VI. To identify biomarkers of response to chemotherapy by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.
VII. To evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT based biomarkers of response to chemotherapy in patients with DLBCL.
VIII. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.
IX. To establish a standardized protocol for FDG-PET/CT image acquisition. X. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor maximum standard uptake value [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.
XI. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||524 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas|
|Actual Study Start Date :||May 2005|
|Actual Primary Completion Date :||October 2017|
|Actual Study Completion Date :||November 15, 2021|
Active Comparator: Arm A - R-CHOP
Patients receive the following treatment:
Required ancillary medications is administered during all cycles as defined in the protocol.
Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.
IV or CIVI
IV or CIVI
Experimental: Arm B - DA-EPOCH-R
Patients receive the following treatment:
Cycle 1 Doses:
Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.
Required ancillary medications are administered during all cycles as defined in the protocol.
Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.
IV or CIVI
IV or CIVI
- Progression-Free Survival Rate at 2 and 5 Years [ Time Frame: Up to 5 years post-registration ]
Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse>
- ≥ 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.>
- Appearance of any new lesion during or after completion of therapy.>
- PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.>
The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.
- Response Rate [ Time Frame: Up to 5 years post-registration ]The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)
- Overall Survival Rate at 2 and 5 Years [ Time Frame: Up to 5 years post-registration ]Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.
- Whether the Gene Expression Signatures That Were Previously Associated With Survival Following CHOP Therapy Are Associated With Survival in Either of the Treatment Arms of the Prospective Trial [ Time Frame: Up to 5 years post-registration ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00118209
|Study Chair:||Wyndham H. Wilson, MD, PhD||National Cancer Institute (NCI)|
|Study Chair:||Andrew D. Zelenetz, MD, PhD||Memorial Sloan Kettering Cancer Center|