Lymphoma, Large B-Cell, Diffuse
Conditions
Keywords
Lymphoma, Large B-Cell, Diffuse, liposomal doxorubicin, doxorubicin, event-free survival
Brief summary
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.
Interventions
DRUGPegylated liposomal doxorubicin
30 mg/m2, IV (in the vein) on day 1 of each 21 day cycle
DRUGDoxorubicin
50 mg/m2, IV (in the vein) on day 1 of each 21 day cycle
DRUGRituximab
375 mg/m2, IV (in the vein) on day 0 of each 21 day cycle
DRUGCyclophophamide
750 mg/m2, IV (in the vein) on day 1 of each 21 day cycle
DRUGVincristine
1.4 mg/m2 (2mg in maxium), IV (in the vein) on day 1 of each 21 day cycle
DRUGPrednisone
100mg/d, PO on day 1-5 of each 21 day cycle
Sponsors
Wenqi Jiang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| event-free survival (EFS) | two year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate (ORR) | at week 6, 12, 18, and 24 after randomization | 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 |
| complete remission (CR) rate | at week 6, 12, 18, and 24 after randomization | 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 |
| overall survival (OS) | two year | defined as time from the date of randomization to the date of death due to any cause or the most recent follow-up |
Countries
China
Contacts
Primary ContactWen-qi Jiang, M.D.
Backup ContactXi-wen Bi, M.D.
Outcome results
None listed