Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin's Lymphoma

NCT02268045 | Completed Phase 3 Results DMC

• 1 other identifier: RTXM83-AC-01-11
• Study Type: interventional
• Target: 272
• Locations: 12 countries
• Sites: 87

Brief Summary

This is a multicenter, double-blind, randomized study comparing the efficacy, pharmacokinetics (PK)/pharmacodynamics (PD), safety and immunogenicity profile of RTXM83 (rituximab biosimilar) vs reference rituximab (MabThera®), both with CHOP, as first-line treatment of Diffuse-Large-B-Cell-Lymphoma (DLBCL). Rituximab biosimilar and MabThera® were both administered intravenously on Day 1 of each 3-week cycle with CHOP chemotherapy for six cycles. Two additional cycles of treatment were permitted at the Investigator's discretion. Patients were followed up for 9 months after last study dose.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Non-Hodgkin Lymphoma; DLBCL; Diffuse large b-cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL

  Per International Working Group (IWG) revised criteria for Malignant Lymphomas (Cheson et al. 2007) and assessed by positron-emission tomography scan, or by computed tomography scan and/or magnetic resonance imaging if Positron Emission Tomography (PET) scan was not feasible. Tumor response was classified according to the International Working Group criteria, as Complete Remission (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; Partial Response (PR): At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses; Stable disease (SD) or; Progressive disease. Response rate was the sum of CR and PR.

  Tumor response assessed after Cycle 6 or at the end of treatment

Secondary Outcomes (8)

• AUC 0-∞ (h μg/mL) at Cycle 1 of RTXM83 and Mabthera®

  Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15

• AUC 0-∞ (h μg/mL) at Cycle 6 of RTXM83 and Mabthera®

  Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21

• Cmax (μg/mL) at Cycle 1 of RTXM83 and Mabthera®

  Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15

• Cmax (μg/mL) at Cycle 6 of RTXM83 and Mabthera®

  Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21

• Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera®

  Up to follow-up 3 (FU3); 9 months after last dose of treatment

Study Arms (2)

RTXM83

EXPERIMENTAL

Active Ingredient: Rituximab (Biosimilar)

Biological: RTXM83

MabThera

ACTIVE COMPARATOR

Active Ingredient: Rituximab

Biological: Mabthera

Interventions

RTXM83 BIOLOGICAL

Rituximab biosimilar (RTXM83) will be administered in combination with CHOP chemotherapy regimen (Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 up to a maximum of 2 mg on Day 1 plus Prednisone 40 mg/m2 or 100 mg per day from Day 1 to 5) at a dose of 375 mg/m2 on Day 1 of each 3 week cycle, for 6 cycles, although the administration of 2 additional cycles may be allowed.

Also known as: Rituximab Biosimilar

RTXM83

Mabthera BIOLOGICAL

Mabthera will be administered in combination with CHOP chemotherapy regimen (Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 up to a maximum of 2 mg on Day 1 plus Prednisone 40 mg/m2 or 100 mg per day from Day 1 to 5) at a dose of 375 mg/m2 on Day 1 of each 3 week cycle, for 6 cycles, although the administration of 2 additional cycles may be allowed.

Also known as: Reference rituximab

MabThera

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with measurable disease defined as existence of a unidimensional or bidimensional lesion greater than 2 cm in its longest diameter or malignant lymphocytosis greater than 5x109/L. Any other procedure for measurable disease in particular cases, may be allowed upon Sponsor approval
• Newly diagnosed patients with a confirmed pathologic diagnosis of Diffuse large B cell-non-Hodgkin's lymphoma (DLBCL) with untreated CD20+ receptor (CD20+). Defined by the local Haematopathologist at the local laboratory according to World Health Organization (WHO) criteria
• Stage II-III or IV or stage I with bulk defined by the referring physician on the basis of the Cotswolds modification of the Ann Arbor classification 2
• Age-adjusted International Prognostic Index (IPI) score 0 or 1
• Age ≥18 to ≤65 years of age
• Performance status according to Eastern Cooperative Oncology Group (ECOG) of ≤2
• Written informed consent obtained before starting any study-specific procedure
• Females of child-bearing potential must test negative on standard serum pregnancy test and must be willing to practice appropriate contraceptive methods for the duration of the study (e.g. oral contraceptive, double barrier method, intra-uterine device, intra-muscular contraceptive)
• All male patients must take adequate contraceptive precautions during the course of the study

You may not qualify if:

• Life expectancy of less than three months
• Any other lymphoma other than CD20+ DLBCL
• Indolent lymphoma, Primary central nervous system (CNS) Lymphoma or gastro-intestinal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma
• Known hypersensitivity to active ingredients, excipients and murine and foreign proteins
• Concurrent disease or general status that would exclude giving the treatment as outlined in the protocol
• Active uncontrolled infection requiring systemic treatment with antibiotics or antiviral agents at Screening or history of documented recurrent clinically significant infection (e.g. 2 or more viral, bacterial or fungal infections requiring inpatient treatment)
• Cardiac contra-indication to Doxorubicin therapy: non-compensated heart failure, dilated cardiomyopathy, coronary heart disease with ST segment depression on electrocardiogram (ECG), myocardial infarction in the last 6 months
• Neurologic contra-indication to Vincristine as it is indicated in the Summary of Product Characteristics (SmPC): (e.g. peripheral neuropathy)
• Chronic lung disease with hypoxemia measured by pulse oximetry (gasometry is not mandatory)
• Severe uncontrolled hypertension, despite optimal medical treatment
• Severe uncontrolled diabetes mellitus, despite optimal medical treatment
• Renal insufficiency (Serum Creatinine \>2 x Upper Normal Limit \[UNL\])
• Hepatic insufficiency: aspartate aminotransferase (AST)/ alanine aminotransferase (ALT)\>3 x UNL or \>5 x UNL with involvement of the liver, total bilirubin \>34.2 µmol/L, or both) not related to lymphoma
• Clinical signs of cerebral dysfunction
• Severe psychiatric disease

Sponsors & Collaborators

• mAbxience Research S.L.: lead
• Pisa® Farmacéutica: collaborator
• Laboratorios de Productos Éticos C.E.I.S.A.: collaborator
• Laboratorio Elea Phoenix S.A.: collaborator
• Tecnoquimicas S.A: collaborator
• Innogene Kalbiotech Pte. Ltd: collaborator
• Libbs Farmacêutica LTDA: collaborator
• Key Oncologics (Pty) Ltd: collaborator
• Nanolek LLC: collaborator
• Actoverco: collaborator

Study Sites (87)

Hosp. Interzonal "R" Carrillo

Ciudadela, Bariloche, Argentina

Location

Clinica Radiologica del Sur

Cipolletti, Río Negro Province, Argentina

Location

Clinica Viedma

Viedma, Río Negro Province, Argentina

Location

Hospital Britanico

Buenos Aires, Argentina

Location

Hospital Gral. de Agudos Donación Francisco Santojanni

Buenos Aires, Argentina

Location

Instituto Roffo

Buenos Aires, Argentina

Location

Centro Oncologico Riojano Integral (CORI)

Córdoba, Argentina

Location

Hospital Nacional de Clinicas

Córdoba, Argentina

Location

Hospital Privado de Cordoba

Córdoba, Argentina

Location

Sanatorio Allende

Córdoba, Argentina

Location

Ctr. Oncologico de Rosario

Rosario, Argentina

Location

Inst. Cardiovascular Rosario

Rosario, Argentina

Location

Instituto de Hematología y Medicina Clínica Dr. Rubén Dávoli

Rosario, Argentina

Location

Sanatorio Parque

Rosario, Argentina

Location

Hospital Angel Padilla

San Miguel de Tucumán, Argentina

Location

Fundación ARS Médica

San Salvador de Jujuy, Argentina

Location

Hospital J. B. Iturraspe

Santa Fe, Argentina

Location

Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, Brazil

Location

Hospital da Cidade de Passo Fundo

Passo Fundo, Rio Grande do Sul, Brazil

Location

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital Clinicas Porto Alegre

Pôrto Alegre, Rio Grande do Sul, Brazil

Location

Hospital Santa Marcelina

Itaquera, São Paulo, Brazil

Location

Hospital Amaral Carvalho Jaú

Jaú, São Paulo, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo-HCFMRP

Ribeirão Preto, São Paulo, Brazil

Location

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia / Faculdade de Medicina do ABC

Santo André, São Paulo, Brazil

Location

Fundação Antônio Prudente - AC Camargo Câncer Center

São Paulo, São Paulo, Brazil

Location

Hospital das Clinicas-UFMG

Belo Horizonte, Brazil

Location

UNICAMP-Univ Zeferino Vaz

Campinas, Brazil

Location

Hospital Uniao Oeste Paranaense de Estudos e Comabte ao Cancer (UOPECCAN)

Cascavel, Brazil

Location

Hospital Erasto Gaertner CEPEP

Curitiba, Brazil

Location

Hospital das Clínicas da Universidade Federal de Goiás

Goiânia, Brazil

Location

Santa Casa de Porto Alegre

Porto Alegre, Brazil

Location

Hospital Universitário Clemente Fraga Filho - UFRJ

Rio de Janeiro, Brazil

Location

Instituto COI de Educação e Pesquisa

Rio de Janeiro, Brazil

Location

Instituto Est. de Hematologia Arthur de Siqueira Cavalcanti

Rio de Janeiro, Brazil

Location

Monte Tabor - Hospital São Rafael

Salvador, Brazil

Location

Hospital de Base de São José

São José do Vale do Rio Preto, Brazil

Location

Centro de Pesquisa do Instituto Brasileiro de Controle do Câncer - IBCC

São Paulo, Brazil

Location

Hospital Clinica Faculdade Medicina USP

São Paulo, Brazil

Location

Inst. Nacional de Cancerologia

Bogotá, Colombia

Location

Fundación Valle de Lili

Cali, Colombia

Location

Hospital Pablo Tobon Uribe

Medellín, Colombia

Location

Srinivasam Cancer Care Hospital

Bangalore, India

Location

Cancer Institute

Chennai, India

Location

Rajiv Gandhi Cancer Institute and Research Centre

Delhi, India

Location

Bibi General Hospital&Canc Ct

Hyderabad, India

Location

Birla Cancer Center - SMS Hospital

Jaipur, India

Location

Health Point Multi-specialty Hospital

Kolkata, India

Location

Institute of Hematology and Transfusion Medicine

Kolkata, India

Location

Netaji Subhash Chandra Bose Cancer Research Institute

Kolkata, India

Location

Acharya Tulsi Regional Cancer Treatment and Research Institute

Madurai, India

Location

Guru Hospital

Madurai, India

Location

Meenakshi Mission Hospital

Madurai, India

Location

Kailash Cancer Hospital and Research Centre

Vadodara, India

Location

Dr. Hasan Sadikin Hospital

Bandung, Indonesia

Location

Dharmais N. C. Center

Jakarta, Indonesia

Location

Imam Khomeini Complex Hospital - Cancer Institute

Tehrān, Iran

Location

Hospital Sultanah Aminah

Johor Bahru, Malaysia

Location

University Malaya Medical Centre - UMMC

Kuala Lumpur, 59100, Malaysia

Location

Mount Miriam Cancer Hospital

Pulau Pinang, 11200, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, Malaysia

Location

Insituto Nacional de Cancerología

Mexico City, Mexico

Location

Instituto Privado de Hematologia e Investigaciona Clinica

Asunción, Paraguay

Location

Cebu Doctors University Hospital

Cebu, Philippines

Location

Perpetual Succour Hospital

Cebu, Philippines

Location

Davao Doctors Hospital

Davao City, Philippines

Location

National Kidney and Transplant Institute

Quezon City, Philippines

Location

Veterans Memorial Medical Center

Quezon City, Philippines

Location

Arkhangelsk Clinical Oncology Dispensary

Arkhangelsk, Russia

Location

Kursk regional clinical oncology dispensary

Kursk, Russia

Location

N.N. Blokhin Russian Cancer Research Cente

Moscow, Russia

Location

National Medical Surgical Center n.a. N.I. Pirogov

Moscow, Russia

Location

Murmansk regional oncology dispensary

Murmansk, Russia

Location

State Budgetary Healthcare Institution of Stavropol region "Pyatigorsk oncology center"

Pyatigorsk, Russia

Location

Rostov Scientific Research Oncology Institute

Rostov-on-Don, Russia

Location

Russian Research Center for Radiology and Surgical Technologies

Saint Petersburg, Russia

Location

Saint-Petersburg State Budgetary Institution "City Clinical Oncology Dispensary"

Saint Petersburg, Russia

Location

Scientific Research Institute of Oncology n.a. N.N. Petrov

Saint Petersburg, Russia

Location

Oncology Center # 2

Sochi, Russia

Location

Komi Republican Oncology Dispensary

Syktyvkar, Russia

Location

State Healthcare Institution of Tula region "Tula regional clinical hospital"

Tula, Russia

Location

Republican Clinical Oncology Dispensary

Ufa, Russia

Location

Volgograd Regional Clinical Oncology Center

Volgograd, Russia

Location

Tygerberg Academic Hosp

Cape Town, South Africa

Location

Rainbow Oncology Centre

eManzimtoti, South Africa

Location

GVI Oncology

Port Elizabeth, South Africa

Location

Chris Hani Baragwanath Hospital

Soweto, South Africa

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; 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

Results Point of Contact

• Title: Susana Millan
• Organization: mAbxience

Susana.Millan@mabxience.com

+34917711500

Study Officials

• Susana Millán, Phd

  mAbxience Research S.L.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2014
• First Posted: October 20, 2014
• Study Start: May 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: July 1, 2017
• Last Updated: September 26, 2019
• Results First Posted: September 26, 2019

Record last verified: 2019-08

Locations

IN (12); AR (17); IR (1); ME (1); RU (15); PA (1); PH (5); MY (4); BR (22); ZA (4); CO (3); ID (2)