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

NCT03018626 | Unknown Phase 3 DMC

• 1 other identifier: NFL2016-B1
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 1

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

Conditions

Lymphoma, Large B-Cell, Diffuse

Keywords

Non-germinal b-cell-like; R-ACVBP; DA-EPOCH-R

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  3 years

Secondary Outcomes (2)

• Overall survival

  3 years

• Complete remission rate

  about 13 weeks after initial chemotherapy

Study Arms (2)

DA-EPOCH-R

ACTIVE COMPARATOR

DA-EPOCH-R regimen: rituximab (375 mg/m2) given intravenously (IV) on day 0, etoposide(50 mg/m2), doxorubicin(10 mg/m2) and vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours), cyclophosphamide(750 mg/m2)/dayg IV on days 5, prednisone (60 mg/m2) given orally bid on days 1 through to 5.All patients received granulocyte colony-stimulating factor (G-CSF) beginning on day 6 and continued until the ANC was more than 5 × 109/L above the nadir level. The adjustment paradigm was based on the ANC nadir in the previous cycle as previously described(Wilson, Grossbard et al. 2002)

Drug: Rituximab; Drug: Etoposide; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Prednisone

Modified R-ACVBP

EXPERIMENTAL

R-ACVBP regimen: rituximab (375 mg/m2) given intravenously (IV) on day 0, doxorubicin (75 mg/m2) and cyclophosphamide (1,200 mg/m2) given intravenously (IV) on day 1, vindesine (2 mg/m2) given on days 1 and 5, bleomycin (10 mg) given IV on days 1 and 5, prednisone (60 mg/m2) given orally on days 1 through to 5.

Drug: Rituximab; Drug: Prednisone; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Vindesine; Drug: Bleomycin

Interventions

Rituximab DRUG

rituximab (375 mg/m2) given intravenously (IV) on day 0

DA-EPOCH-R; Modified R-ACVBP

Etoposide DRUG

Etoposide(50 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)

DA-EPOCH-R

Doxorubicin DRUG

Doxorubicin(10 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)

DA-EPOCH-R

Vincristine DRUG

Vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)

DA-EPOCH-R

Cyclophosphamide DRUG

Cyclophosphamide(750 mg/m2)/dayg IV on days 5

DA-EPOCH-R

Prednisone DRUG

prednisone (100 mg) given orally bid on days 1 through to 5.

DA-EPOCH-R; Modified R-ACVBP

Vindesine DRUG

Vindesine (2 mg/m2) given on days 1 and 5

Modified R-ACVBP

Bleomycin DRUG

Bleomycin (10 mg) given IV on days 1 and 5

Modified R-ACVBP

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Ru Feng

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (10)

• 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. doi: 10.1182/blood.v99.8.2685.

  PMID: 11929754 BACKGROUND

• Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, Thieblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquieres 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.

  PMID: 22118442 BACKGROUND

• 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.

  PMID: 21546499 BACKGROUND

• Molina TJ, Canioni D, Copie-Bergman C, Recher C, Briere J, Haioun C, Berger F, Ferme 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.

  PMID: 25385729 BACKGROUND

• 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.

  PMID: 22133772 BACKGROUND

• 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.

  PMID: 18378569 BACKGROUND

• Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, Garcia-Marco JA, Castellvi 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.

  PMID: 25521006 BACKGROUND

• 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. doi: 10.1016/j.leukres.2007.03.017. Epub 2007 Apr 19.

  PMID: 17448534 BACKGROUND

• Gutierrez-Garcia G, Cardesa-Salzmann T, Climent F, Gonzalez-Barca E, Mercadal S, Mate JL, Sancho JM, Arenillas L, Serrano S, Escoda L, Martinez S, Valera A, Martinez A, Jares P, Pinyol M, Garcia-Herrera A, Martinez-Trillos A, Gine E, Villamor N, Campo E, Colomo L, Lopez-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.

  PMID: 21441466 BACKGROUND

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

  PMID: 20393178 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Etoposide; Doxorubicin; Vincristine; Cyclophosphamide; Prednisone; Vindesine; Bleomycin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Glycopeptides; Glycoconjugates; Peptides

Study Officials

• Ru Feng, M.D.

  Department of Hematology, Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ru Feng, M.D.

CONTACT

ruth1626@hotmail.com

Xiaolei Wei, PH.D.

CONTACT

smuxiaoleiwei@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: January 12, 2017
• Study Start: July 27, 2017
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2021
• Last Updated: July 28, 2017

Record last verified: 2017-07

Locations

CN (1)