Lymphoma, Large B-Cell, Diffuse
Conditions
Keywords
Non-germinal b-cell-like, R-ACVBP, DA-EPOCH-R
Brief summary
This is a randomized, open-label, multi-center, phase 3 study evaluating the efficacy of R-ACVBP and DA-EPOCH-R in patients with newly diagnosed non-germinal b-cell-like diffuse large B-cell lymphoma
Detailed description
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. According to Hans' algorithms, DLBCL can be identified as 2 subtypes: germinal b-cell-like(GCB) and non-germinal b-cell-like(non-GCB). Approximately 50 to 60% of diffuse large-B cell lymphoma(DLBCL) was non-GCB subtype DLBCL. Although the introduction of rituximab in immunochemotherapy has dramatically improved the outcome of patients with DLBCL, The survival was still poor in non-GCB DLBCL patients treated with R-CHOP. The LNH03-2B study has shown that R-ACVBP regimen gave a longer PFS (93% vs. 74% at 3 years, p=0.0074) and a longer OS (97% vs. 83% at 3 years, p=0.0067) than R-CHOP in young patients with non-GCB DLBCL. It also showed that R-ACVBP regimen gave a longer PFS (87% vs. 73% at 3 years, p=0.0074) and a longer OS (92% vs. 84% at 3 years, p=0.0067) than R-CHOP in young low-intermediate risk DLBCL patients. The LNH2003-3 study has shown that in high-risk (2/3 IPI factors) DLBCL patients treated with R-ACVBP followed by auto-ASCT results in a 74% PFS and 76% OS. Hematological toxic effects of the intensive regimen were raised but manageable. The CALGB study showed that in DLBCL patients at least 18 years of age and at least stage II, DA-EPOCH-R regimen is effective in both GCB and non-GCB subtypes, with a 5-years TTP 67%, EFS 58% and OS 68% in non-GCB subtype DLBCL. It is encouraging that PETHEMA Group study showed that in the long-term follow-up of untreated DLBCL patients with poor prognosis, DA-EPOCH-R achieved a 70.8% EFS and 76.4% OS at 10 years in non-GCB subtype DLBCL. However the efficacy of R-ACVBP compared to DA-EPOCH-R in patients with newly diagnosed non-germinal b-cell-like diffuse large B-cell lymphoma remains unknown. All the above-mentioned results led us to propose a randomized trial comparing R-ACVBP to DA-EPOCH-R in previously untreated patients with non-GCB DLBCL.
Interventions
DRUGRituximab
rituximab (375 mg/m2) given intravenously (IV) on day 0
DRUGEtoposide
Etoposide(50 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)
DRUGDoxorubicin
Doxorubicin(10 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)
DRUGVincristine
Vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)
DRUGCyclophosphamide
Cyclophosphamide(750 mg/m2)/dayg IV on days 5
DRUGPrednisone
prednisone (100 mg) given orally bid on days 1 through to 5.
DRUGVindesine
Vindesine (2 mg/m2) given on days 1 and 5
DRUGBleomycin
Bleomycin (10 mg) given IV on days 1 and 5
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patient with histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification), * aaIPI\>1, * Age \>18 and \< 61 years, * Negative HIV serologies 4 weeks * Ability to understand and willingness to sign a written informed consent
Exclusion criteria
* Any other histological type of lymphoma. Any history of treated or non-treated indolent lymphoma. * Central nervous system or meningeal involvement by lymphoma. * Contraindication to any drug contained in the chemotherapy regimens. * Any serious active disease (according to the investigator's decision). * Poor renal function (creatinin level\>150µmol/l), poor hepatic function (total bilirubin level\>30mmol/l, transaminases\>2.5 maximum normal level) unless these abnormalities are related to the lymphoma. * Poor bone marrow reserve as defined by neutrophils \<1.5 G/l or platelets \<100 G/l, unless related to bone marrow infiltration. * Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study. * Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 3 years | — |
| Complete remission rate | about 13 weeks after initial chemotherapy | 4 cycles after chemotherapy |
Countries
China
Contacts
Primary ContactRu Feng, M.D.
Backup ContactXiaolei Wei, PH.D.
Outcome results
None listed