R-CHOP Versus R-CDOP as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma

Study Overview
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Brief Summary
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The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP regimen) has been the first-line chemotherapy for elderly patients with diffuse large B-cell lymphoma (DLBCL). The treatment-related toxicities, especially the severe cardiac toxicities induced by anthracycline drugs (doxorubicin), have become a major concern among elderly patients. Pegylated liposomal doxorubicin is a formulation of doxorubicin with a prolonged circulation time and unique toxicity profile. Previous single arm studies of elderly patients with lymphoma used pegylated liposomal doxorubicin instead of traditional doxorubicin in combination with rituximab, cyclophosphamide, vincristine, and prednisone (the novel R-CDOP regimen), and demonstrated better safety profile, including less bone marrow suppression and less cardiac toxicities, while maintaining the efficacy. However, the efficacy and safety of these two regimens (R-CHOP and R-CDOP) have not been head-to-head compared in a randomized study. The aim of this study is to compare the efficacy and safety of R-CDOP (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated elderly patients with DLBCL.

Official Title
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Rituximab, Cyclophosphamide, Vincristine, and Prednisone in Combination With Doxorubicin (R-CHOP) Versus in Combination With Pegylated-liposomal Doxorubicin (R-CDOP) as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma: a Randomised, Multicentre, Non-inferiority Study

Conditions
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Lymphoma, Large B-Cell, Diffuse

Intervention / Treatment
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* Drug: Pegylated liposomal doxorubicin
* Drug: Doxorubicin
* Drug: Rituximab
* Drug: Cyclophophamide
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed diagnosis of CD20-positive diffuse large B-cell lymphoma 60 80 years old Ann Arbor stage I IV ECOG physical score of 0 2 Have not received previous treatment to lymphoma, including chemotherapy, radiotherapy, or biotherapy Have at least one clinically measurable lesion: >= 2cm under physical examination, or >= 1.5cm under computed tomography (CT) or magnetic resonance (MR) Life expectancy of >= 3 months Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase and total bilirubin <= 2 × upper limit of normal (ULN) Glomerular filtration rate (MDRD method) >= 30ml/min No abnormalities in blood coagulative function Generally normal bone marrow function: while blood cell >= 3,000/μL, absolute neutrophil count >= 1,500/μL, hemoglobin >= 100g/L, platelet >= 75,000/μL No evidence of active hepatitis B or C virus, or human immunodeficiency virus infection Left ventricular ejection fraction (LVEF) >= 45% measured by two dimensional echocardiography or multi-gated acquisition (MUGA) scan Cardiac function of class I-II in New York Heart Association (NYHA) classification Exclusion Criteria: Patients with indolent lymphoma Positive results for in situ hybridization for Epstein-Barr virus encoded RNA (EBER) Serum Epstein-Barr virus DNA >= 1,000 copies/ml Double-hit lymphoma confirmed by fluorescence in situ hybridization (FISH) Primary mediastinal B-cell lymphoma Involvement of central nervous system Bulky disease (>= 10cm) History of cardiac disease, including clinically significant ventricular tachycardia, atrial fibrillation, conduction block, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease which needs medication Known allergic reaction to any component of the agents used in the chemotherapeutic regimens that are used in the study Previous exposure to anthracycline drugs, rituximab, or chemotherapy for lymphoma History of malignant carcinoma within 5 years (except carcinoma in situ of the skin and uterine cervix, and prostatic carcinoma) Currently enrolled in other clinical studies Other conditions that the investigators consider as inappropriate for enrolling into this study

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: R-CHOP<br>This group received R-CHOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Doxorubicin, 50mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met. | Drug: Doxorubicin<br>* 50 mg/m2, IV (in the vein) on day 1 of each 21 day cycle<br>Drug: Rituximab<br>* 375 mg/m2, IV (in the vein) on day 0 of each 21 day cycle<br>Drug: Cyclophophamide<br>* 750 mg/m2, IV (in the vein) on day 1 of each 21 day cycle<br>Drug: Vincristine<br>* 1.4 mg/m2 (2mg in maxium), IV (in the vein) on day 1 of each 21 day cycle<br>Drug: Prednisone<br>* 100mg/d, PO on day 1-5 of each 21 day cycle<br>|
| Experimental: R-CDOP<br>This group received R-CDOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Pegylated liposomal doxorubicin, 30mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met. | Drug: Pegylated liposomal doxorubicin<br>* 30 mg/m2, IV (in the vein) on day 1 of each 21 day cycle<br>Drug: Rituximab<br>* 375 mg/m2, IV (in the vein) on day 0 of each 21 day cycle<br>Drug: Cyclophophamide<br>* 750 mg/m2, IV (in the vein) on day 1 of each 21 day cycle<br>Drug: Vincristine<br>* 1.4 mg/m2 (2mg in maxium), IV (in the vein) on day 1 of each 21 day cycle<br>Drug: Prednisone<br>* 100mg/d, PO on day 1-5 of each 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event-free survival (EFS) | Defined as time from the date of randomization to the date of disease progression, death due to any cause, termination of treatment, or the most recent follow-up | two year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR) | defined as the proportion of patients whose best overall response is either complete remission (CR) or partial remission (PR), which was evaluated in accordance with the International Working Group Recommendations for Response Criteria for non-Hodgkin's lymphoma | at week 6, 12, 18, and 24 after randomization | 
| complete remission (CR) rate | defined as the proportion of patients whose best overall response is complete remission, which was evaluated in accordance with the International Working Group Recommendations for Response Criteria for non-Hodgkin's lymphoma | at week 6, 12, 18, and 24 after randomization | 
| overall survival (OS) | defined as time from the date of randomization to the date of death due to any cause or the most recent follow-up | two year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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doxorubicin, Lymphoma, Large B-Cell, Diffuse, liposomal doxorubicin, event-free survival