R-CHOP Alone vs. R-CHOP Plus Radiotherapy for Localized CD20+ DLBCL

Study Overview
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Brief Summary
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To compare the efficacy and safety of chemotherapy alone and combined modality therapy in the treatment of localized CD20 (+) diffuse large B-cell lymphoma

Official Title
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Randomized Phase III Trial Comparing R-CHOP Alone and R-CHOP Plus Radiotherapy for Localized CD20+ Diffuse Large B-cell Lymphoma (DLBCL)

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: R-CHOP
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Histologically confirmed CD20-positive Diffuse Large B-cell Lymphoma (DLBCL), NOS Immunostains for CD20, CD5, CD3, CD10, MUM-1, BCL-6, BCL-2 and Ki-67 and the in situ hybridization for Epstein-Barr virus are recommended for diagnosis of DLBCL, NOS. No prior treatment for DLBCL Stage I or contiguous II disease (Involvement of two adjacent lymph node regions or organ involvement with regional lymph nodes) Performance status: ECOG 0-2. Age ≥ 18 years Cardiac ejection fraction ≥ 45% as measured by MUGA or 2D ECHO without clinically significant abnormalities Adequate renal function: serum creatinine level < 2 mg/dL Adequate liver functions Adequate hematological function: hemoglobin ≥ 9.0 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone marrow involvement by lymphoma Life expectancy >= 6 months A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause. Female patients of child bearing potential must use an effective method of birth control (i.e. hormonal contraceptive, intrauterine device,diaphragm with spermicide, condom with spermicide or abstinence) during treatment period and 1 month thereafter; Males must use an effective method of birth control during treatment period and 3 months thereafter. Exclusion Criteria: Other subtypes NHL than CD20 (+) DLBCL, NOS Transformed DLBCL from follicular lymphoma or other indolent lymphomas Bulky disease ( longest diameter >=10 cm) Previous treatment for DLBCL with immunotherapy or chemotherapy except for short-term corticosteroids (duration of ≤ 8 days) before inclusion CNS involvement by lymphoma or any evidence of spinal cord compression. Primary Central Nervous System (CNS) DLBCL Primary testicular lymphoma Primary breast lymphoma Patients with a known history of HIV seropositivity or HCV (+). (Patients who have HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine, etc) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period.) Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin, early gastric cancer or carcinoma in situ of the cervix or breast or untreated prostatic cancer without any plan for a treatment) unless the patient has been free of the disease for ≥ 3 years Pregnant or lactating women Men who are not surgically sterile and women of childbearing potential not employing adequate contraception Other serious illness or medical conditions Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry History of significant neurological or psychiatric disorders including dementia or seizures Active uncontrolled infection (viral, bacterial or fungal infection) Other serious medical illnesses Known hypersensitivity to any of the study drugs or its ingredients Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Total 6 cycles of R-CHOP<br> | Drug: R-CHOP<br>* R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or prednisolone))<br>|
| Experimental: Total 3 cycles of R-CHOP + RT<br>Total 3 cycles of R-CHOP followed by radiotherapy (involved field or involved site radiotherapy, 30-50 Gy/ 15-25 fractions) | Drug: R-CHOP<br>* R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or prednisolone))<br>Radiation: Radiotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare 3-year event-free survival | definition of events: failure to achieve CR after completion of planned 1st-line treatment, progression of disease, relapse, institution of a new anticancer treatment or any cause of death) rate in patients with CD20 (+) diffuse large B-cell lymphoma treated with either R-CHOP chemotherapy alone or R-CHOP plus radiotherapy | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate and compare OS between the two arms |  | 3 years | 
| To evaluate and compare the ORR and CR rate |  | after completion of treatment | 
| To evaluate and compare disease-free survival (DFS) |  | 3 years | 
| To evaluate treatment-failure pattern |  | 3 years | 
| Number of Participants with Adverse Events in each arm |  | 3 years | 
| To assess patient-reported outcomes (PROs) in both arms |  | 3 years | 
| A role of interim PET after 3 cycles of R-CHOP chemotherapy: correlation with PFS and OS |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized, diffuse large B-cell lymphoma, R-CHOP chemotherapy, radiotherapy