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

NCT ID: NCT02268045

Last Updated: 2019-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2017-07-31

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.

Detailed Description

The primary endpoint of the investigation is to determine if the response rate obtained with RTXM83 combined with CHOP is non inferior to the response rate obtained with reference rituximab combined with CHOP.

The present study is a non inferiority trial and the study hypothesis is the following: H0: pc ≥ pe + δ vs. H1: pc < pe + δ where, pe: proportion of successes in the experimental group (RTXM83+CHOP) pc: proportion of successes in the control group (Reference Rituximab+CHOP) Type I error: the difference pc-pe is less than δ when in fact the difference is greater than or equal to δ ie, the investigators choose the experimental treatment when the control treatment is actually substantially better.

Type II error: the difference -pe is greater than or equal to δ when it is actually lest than δ ie, the investigators choose the control treatment when the experimental treatment is essentially just as good.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

RTXM83

Active Ingredient: Rituximab (Biosimilar)

Group Type: EXPERIMENTAL

RTXM83

Intervention Type: 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.

MabThera

Active Ingredient: Rituximab

Group Type: ACTIVE_COMPARATOR

Mabthera

Intervention Type: 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.

Interventions

RTXM83

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.

Intervention Type: BIOLOGICAL

Mabthera

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Rituximab Biosimilar; Reference rituximab

Eligibility Criteria

Inclusion Criteria

1. 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

2. 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

3. 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

4. Age-adjusted International Prognostic Index (IPI) score 0 or 1

5. Age ≥18 to ≤65 years of age

6. Performance status according to Eastern Cooperative Oncology Group (ECOG) of ≤2

7. Written informed consent obtained before starting any study-specific procedure

8. 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)

9. All male patients must take adequate contraceptive precautions during the course of the study

Exclusion Criteria

1. Life expectancy of less than three months

2. Any other lymphoma other than CD20+ DLBCL

3. Indolent lymphoma, Primary central nervous system (CNS) Lymphoma or gastro-intestinal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma

4. Known hypersensitivity to active ingredients, excipients and murine and foreign proteins

5. Concurrent disease or general status that would exclude giving the treatment as outlined in the protocol

6. 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)

7. 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

8. Neurologic contra-indication to Vincristine as it is indicated in the Summary of Product Characteristics (SmPC): (e.g. peripheral neuropathy)

9. Chronic lung disease with hypoxemia measured by pulse oximetry (gasometry is not mandatory)

10. Severe uncontrolled hypertension, despite optimal medical treatment

11. Severe uncontrolled diabetes mellitus, despite optimal medical treatment

12. Renal insufficiency (Serum Creatinine >2 x Upper Normal Limit [UNL])

13. 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

14. Clinical signs of cerebral dysfunction

15. Severe psychiatric disease

16. Known human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C

17. Abnormal bone marrow function (platelets <100x109/L, neutrophils <1.5x109/L and Haemoglobin <9g/dL)

18. Post-transplantation lymphoproliferative disease

19. Pregnant or lactating women or women that intend to get pregnant during study or within 12 months following the last infusion

20. Treatment with any investigational product in the 30 days period before inclusion in the study

21. Prior radiotherapy to treat the DLBCL Non-Hodgkin's Lymphoma (NHL)

22. Limitation of the patient's ability to comply with the treatment or follow-up protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pisa® Farmacéutica

UNKNOWN

Sponsor Role: collaborator

Laboratorios de Productos Éticos C.E.I.S.A.

UNKNOWN

Sponsor Role: collaborator

Laboratorio Elea Phoenix S.A.

INDUSTRY

Sponsor Role: collaborator

Tecnoquimicas S.A

UNKNOWN

Sponsor Role: collaborator

Innogene Kalbiotech Pte. Ltd

INDUSTRY

Sponsor Role: collaborator

Libbs Farmacêutica LTDA

INDUSTRY

Sponsor Role: collaborator

Key Oncologics (Pty) Ltd

UNKNOWN

Sponsor Role: collaborator

Nanolek LLC

OTHER

Sponsor Role: collaborator

Actoverco

OTHER

Sponsor Role: collaborator

mAbxience Research S.L.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susana Millán, Phd

Role: STUDY_DIRECTOR

mAbxience Research S.L.

Locations

Hosp. Interzonal "R" Carrillo

Ciudadela, Bariloche, Argentina

Clinica Radiologica del Sur

Cipolletti, Río Negro Province, Argentina

Clinica Viedma

Viedma, Río Negro Province, Argentina

Hospital Britanico

Buenos Aires, , Argentina

Hospital Gral. de Agudos Donación Francisco Santojanni

Buenos Aires, , Argentina

Instituto Roffo

Buenos Aires, , Argentina

Centro Oncologico Riojano Integral (CORI)

Córdoba, , Argentina

Hospital Nacional de Clinicas

Córdoba, , Argentina

Hospital Privado de Cordoba

Córdoba, , Argentina

Sanatorio Allende

Córdoba, , Argentina

Ctr. Oncologico de Rosario

Rosario, , Argentina

Inst. Cardiovascular Rosario

Rosario, , Argentina

Instituto de Hematología y Medicina Clínica Dr. Rubén Dávoli

Rosario, , Argentina

Sanatorio Parque

Rosario, , Argentina

Hospital Angel Padilla

San Miguel de Tucumán, , Argentina

Fundación ARS Médica

San Salvador de Jujuy, , Argentina

Hospital J. B. Iturraspe

Santa Fe, , Argentina

Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, Brazil

Hospital da Cidade de Passo Fundo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Clinicas Porto Alegre

Pôrto Alegre, Rio Grande do Sul, Brazil

Hospital Santa Marcelina

Itaquera, São Paulo, Brazil

Hospital Amaral Carvalho Jaú

Jaú, São Paulo, Brazil

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

Ribeirão Preto, São Paulo, Brazil

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

Santo André, São Paulo, Brazil

Fundação Antônio Prudente - AC Camargo Câncer Center

São Paulo, São Paulo, Brazil

Hospital das Clinicas-UFMG

Belo Horizonte, , Brazil

UNICAMP-Univ Zeferino Vaz

Campinas, , Brazil

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

Cascavel, , Brazil

Hospital Erasto Gaertner CEPEP

Curitiba, , Brazil

Hospital das Clínicas da Universidade Federal de Goiás

Goiânia, , Brazil

Santa Casa de Porto Alegre

Porto Alegre, , Brazil

Hospital Universitário Clemente Fraga Filho - UFRJ

Rio de Janeiro, , Brazil

Instituto COI de Educação e Pesquisa

Rio de Janeiro, , Brazil

Instituto Est. de Hematologia Arthur de Siqueira Cavalcanti

Rio de Janeiro, , Brazil

Monte Tabor - Hospital São Rafael

Salvador, , Brazil

Hospital de Base de São José

São José do Vale do Rio Preto, , Brazil

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

São Paulo, , Brazil

Hospital Clinica Faculdade Medicina USP

São Paulo, , Brazil

Inst. Nacional de Cancerologia

Bogotá, , Colombia

Fundación Valle de Lili

Cali, , Colombia

Hospital Pablo Tobon Uribe

Medellín, , Colombia

Srinivasam Cancer Care Hospital

Bangalore, , India

Cancer Institute

Chennai, , India

Rajiv Gandhi Cancer Institute and Research Centre

Delhi, , India

Bibi General Hospital&Canc Ct

Hyderabad, , India

Birla Cancer Center - SMS Hospital

Jaipur, , India

Health Point Multi-specialty Hospital

Kolkata, , India

Institute of Hematology and Transfusion Medicine

Kolkata, , India

Netaji Subhash Chandra Bose Cancer Research Institute

Kolkata, , India

Acharya Tulsi Regional Cancer Treatment and Research Institute

Madurai, , India

Guru Hospital

Madurai, , India

Meenakshi Mission Hospital

Madurai, , India

Kailash Cancer Hospital and Research Centre

Vadodara, , India

Dr. Hasan Sadikin Hospital

Bandung, , Indonesia

Dharmais N. C. Center

Jakarta, , Indonesia

Imam Khomeini Complex Hospital - Cancer Institute

Tehrān, , Iran

Hospital Sultanah Aminah

Johor Bahru, , Malaysia

University Malaya Medical Centre - UMMC

Kuala Lumpur, , Malaysia

Mount Miriam Cancer Hospital

Pulau Pinang, , Malaysia

Hospital Pulau Pinang

Pulau Pinang, , Malaysia

Insituto Nacional de Cancerología

Mexico City, , Mexico

Instituto Privado de Hematologia e Investigaciona Clinica

Asunción, , Paraguay

Cebu Doctors University Hospital

Cebu, , Philippines

Perpetual Succour Hospital

Cebu, , Philippines

Davao Doctors Hospital

Davao City, , Philippines

National Kidney and Transplant Institute

Quezon City, , Philippines

Veterans Memorial Medical Center

Quezon City, , Philippines

Arkhangelsk Clinical Oncology Dispensary

Arkhangelsk, , Russia

Kursk regional clinical oncology dispensary

Kursk, , Russia

N.N. Blokhin Russian Cancer Research Cente

Moscow, , Russia

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

Moscow, , Russia

Murmansk regional oncology dispensary

Murmansk, , Russia

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

Pyatigorsk, , Russia

Rostov Scientific Research Oncology Institute

Rostov-on-Don, , Russia

Russian Research Center for Radiology and Surgical Technologies

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Oncology Center # 2

Sochi, , Russia

Komi Republican Oncology Dispensary

Syktyvkar, , Russia

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

Tula, , Russia

Republican Clinical Oncology Dispensary

Ufa, , Russia

Volgograd Regional Clinical Oncology Center

Volgograd, , Russia

Tygerberg Academic Hosp

Cape Town, , South Africa

Rainbow Oncology Centre

eManzimtoti, , South Africa

GVI Oncology

Port Elizabeth, , South Africa

Chris Hani Baragwanath Hospital

Soweto, , South Africa

Countries

Argentina; Brazil; Colombia; India; Indonesia; Iran; Malaysia; Mexico; Paraguay; Philippines; Russia; South Africa

Other Identifiers

RTXM83-AC-01-11

Identifier Type: -

Identifier Source: org_study_id