R-ACVBP and DA-EPOCH-R in Patients With Non-GCB DLBCL

Lymphoma, Large B-Cell, Diffuse Clinical Trial

Official title:

Study of R-ACVBP and DA-EPOCH-R in Patients With Newly Diagnosed Non-germinal Center B-cell-like Diffuse Large B-cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03018626
• Other study ID #: NFL2016-B1
• Status: Recruiting
• Phase: Phase 3
• First received: November 2, 2016
• Last updated: July 26, 2017
• Start date: July 27, 2017
• Est. completion date: January 2021

Study information

• Verified date: July 2017
• Source: Nanfang Hospital of Southern Medical University
• Contact: Ru Feng, M.D.
• Email: ruth1626[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 402
• Est. completion date: January 2021
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
rituximab (375 mg/m2) given intravenously (IV) on day 0
• Etoposide
Etoposide(50 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)
• Doxorubicin
Doxorubicin(10 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)
• Vincristine
Vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)
• Cyclophosphamide
Cyclophosphamide(750 mg/m2)/dayg IV on days 5
• Prednisone
prednisone (100 mg) given orally bid on days 1 through to 5.
• Doxorubicin
Doxorubicin (75 mg/m2) given intravenously (IV) on day 1,
• Cyclophosphamide
Cyclophosphamide (1,200 mg/m2) given intravenously (IV) on day 1,
• Vindesine
Vindesine (2 mg/m2) given on days 1 and 5
• Bleomycin
Bleomycin (10 mg) given IV on days 1 and 5

Locations

Country	Name	City	State
China	Ru Feng	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (10)

Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G, Feugier P, Ferme C, Ysebaert L, Gabarre J, Herbrecht R, Janvier M, Van Den Neste E, Morschhauser F, Casasnovas O, Ghesquieres H, Anglaret B, Brechignac S, Haioun C, Gisselbrecht C. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. Haematologica. 2011 Aug;96(8):1136-43. doi: 10.3324/haematol.2010.038109. Epub 2011 May 5. — View Citation

Gutiérrez-García G, Cardesa-Salzmann T, Climent F, González-Barca E, Mercadal S, Mate JL, Sancho JM, Arenillas L, Serrano S, Escoda L, Martínez S, Valera A, Martínez A, Jares P, Pinyol M, García-Herrera A, Martínez-Trillos A, Giné E, Villamor N, Campo E, Colomo L, López-Guillermo A; Grup per l'Estudi dels Limfomes de Catalunya I Balears (GELCAB). Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood. 2011 May 5;117(18):4836-43. doi: 10.1182/blood-2010-12-322362. Epub 2011 Mar 25. — View Citation

Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010 Apr 15;362(15):1417-29. doi: 10.1056/NEJMra0807082. Review. — View Citation

Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. doi: 10.1200/JCO.2013.54.9493. Epub 2014 Nov 10. — View Citation

Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br J Haematol. 2015 Apr;169(2):188-98. doi: 10.1111/bjh.13273. Epub 2014 Dec 18. — View Citation

Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. doi: 10.1016/S0140-6736(11)61040-4. — View Citation

Shiozawa E, Yamochi-Onizuka T, Takimoto M, Ota H. The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian countries. Leuk Res. 2007 Nov;31(11):1579-83. Epub 2007 Apr 19. — View Citation

Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. doi: 10.1200/JCO.2007.13.1391. Epub 2008 Mar 31. — View Citation

Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. — View Citation

Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. doi: 10.3324/haematol.2011.056531. Epub 2011 Dec 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		3 years
Secondary	Overall survival		3 years
Secondary	Complete remission rate	4 cycles after chemotherapy	about 13 weeks after initial chemotherapy