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Diffuse Large B-cell LymphomaPhase 3NCT02268045

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

A Phase 3 study testing RTXM83 and Mabthera in people with Diffuse Large B-cell Lymphoma, run by mAbxience Research S.L. at 87 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
RTXM83 and Mabthera
Could I receive a placebo?
No, everyone receives an active treatment
How many people
272 participants
Where
87 sitesin 12 countries
Study dates
May 2013to Jul 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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)
Show all 22Show fewer
  • 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
  • Known human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C
  • Abnormal bone marrow function (platelets <100x109/L, neutrophils <1.5x109/L and Haemoglobin <9g/dL)
  • Post-transplantation lymphoproliferative disease
  • Pregnant or lactating women or women that intend to get pregnant during study or within 12 months following the last infusion
  • Treatment with any investigational product in the 30 days period before inclusion in the study
  • Prior radiotherapy to treat the DLBCL Non-Hodgkin's Lymphoma (NHL)
  • Limitation of the patient's ability to comply with the treatment or follow-up protocol

Trial locations and contacts

87 sites in 12 countries.

87 sites in 12 countries

Brazil22 sites

  • Hospital das Clinicas-UFMG

    Belo Horizonte

  • UNICAMP-Univ Zeferino Vaz

    Campinas

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

    Cascavel

  • Hospital Erasto Gaertner CEPEP

    Curitiba

  • Hospital das Clínicas da Universidade Federal de Goiás

    Goiânia

  • Hospital de Caridade de Ijuí

    Ijuí, Rio Grande do Sul

  • Hospital Santa Marcelina

    Itaquera, São Paulo

  • Hospital Amaral Carvalho Jaú

    Jaú, São Paulo

  • Hospital da Cidade de Passo Fundo

    Passo Fundo, Rio Grande do Sul

  • Hospital São Lucas da PUCRS

    Porto Alegre, Rio Grande do Sul

  • Santa Casa de Porto Alegre

    Porto Alegre

  • Hospital Clinicas Porto Alegre

    Pôrto Alegre, Rio Grande do Sul

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

    Ribeirão Preto, São Paulo

  • Hospital Universitário Clemente Fraga Filho - UFRJ

    Rio de Janeiro

  • Instituto COI de Educação e Pesquisa

    Rio de Janeiro

  • Instituto Est. de Hematologia Arthur de Siqueira Cavalcanti

    Rio de Janeiro

  • Monte Tabor - Hospital São Rafael

    Salvador

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

    Santo André, São Paulo

  • Hospital de Base de São José

    São José do Vale do Rio Preto

  • Fundação Antônio Prudente - AC Camargo Câncer Center

    São Paulo, São Paulo

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

    São Paulo

  • Hospital Clinica Faculdade Medicina USP

    São Paulo

Other trials in Brazil

Argentina17 sites

  • Hospital Britanico

    Buenos Aires

  • Hospital Gral. de Agudos Donación Francisco Santojanni

    Buenos Aires

  • Instituto Roffo

    Buenos Aires

  • Clinica Radiologica del Sur

    Cipolletti, Río Negro Province

  • Hosp. Interzonal "R" Carrillo

    Ciudadela, Bariloche

  • Centro Oncologico Riojano Integral (CORI)

    Córdoba

  • Hospital Nacional de Clinicas

    Córdoba

  • Hospital Privado de Cordoba

    Córdoba

  • Sanatorio Allende

    Córdoba

  • Ctr. Oncologico de Rosario

    Rosario

  • Inst. Cardiovascular Rosario

    Rosario

  • Instituto de Hematología y Medicina Clínica Dr. Rubén Dávoli

    Rosario

  • Sanatorio Parque

    Rosario

  • Hospital Angel Padilla

    San Miguel de Tucumán

  • Fundación ARS Médica

    San Salvador de Jujuy

  • Hospital J. B. Iturraspe

    Santa Fe

  • Clinica Viedma

    Viedma, Río Negro Province

Other trials in Argentina

Russia15 sites

  • Arkhangelsk Clinical Oncology Dispensary

    Arkhangelsk

  • Kursk regional clinical oncology dispensary

    Kursk

  • N.N. Blokhin Russian Cancer Research Cente

    Moscow

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

    Moscow

  • Murmansk regional oncology dispensary

    Murmansk

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

    Pyatigorsk

  • Rostov Scientific Research Oncology Institute

    Rostov-on-Don

  • Russian Research Center for Radiology and Surgical Technologies

    Saint Petersburg

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

    Saint Petersburg

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

    Saint Petersburg

  • Oncology Center # 2

    Sochi

  • Komi Republican Oncology Dispensary

    Syktyvkar

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

    Tula

  • Republican Clinical Oncology Dispensary

    Ufa

  • Volgograd Regional Clinical Oncology Center

    Volgograd

Other trials in Russia

India12 sites

  • Srinivasam Cancer Care Hospital

    Bangalore

  • Cancer Institute

    Chennai

  • Rajiv Gandhi Cancer Institute and Research Centre

    Delhi

  • Bibi General Hospital&Canc Ct

    Hyderabad

  • Birla Cancer Center - SMS Hospital

    Jaipur

  • Health Point Multi-specialty Hospital

    Kolkata

  • Institute of Hematology and Transfusion Medicine

    Kolkata

  • Netaji Subhash Chandra Bose Cancer Research Institute

    Kolkata

  • Acharya Tulsi Regional Cancer Treatment and Research Institute

    Madurai

  • Guru Hospital

    Madurai

  • Meenakshi Mission Hospital

    Madurai

  • Kailash Cancer Hospital and Research Centre

    Vadodara

Other trials in India

Philippines5 sites

  • Cebu Doctors University Hospital

    Cebu

  • Perpetual Succour Hospital

    Cebu

  • Davao Doctors Hospital

    Davao City

  • National Kidney and Transplant Institute

    Quezon City

  • Veterans Memorial Medical Center

    Quezon City

Other trials in Philippines

Malaysia4 sites

  • Hospital Sultanah Aminah

    Johor Bahru

  • University Malaya Medical Centre - UMMC

    Kuala Lumpur, 59100

  • Mount Miriam Cancer Hospital

    Pulau Pinang, 11200

  • Hospital Pulau Pinang

    Pulau Pinang

Other trials in Malaysia

South Africa4 sites

  • Tygerberg Academic Hosp

    Cape Town

  • Rainbow Oncology Centre

    eManzimtoti

  • GVI Oncology

    Port Elizabeth

  • Chris Hani Baragwanath Hospital

    Soweto

Other trials in South Africa

Colombia3 sites

  • Inst. Nacional de Cancerologia

    Bogotá

  • Fundación Valle de Lili

    Cali

  • Hospital Pablo Tobon Uribe

    Medellín

Other trials in Colombia

Indonesia2 sites

  • Dr. Hasan Sadikin Hospital

    Bandung

  • Dharmais N. C. Center

    Jakarta

Other trials in Indonesia

Iran1 site

  • Imam Khomeini Complex Hospital - Cancer Institute

    Tehrān

Other trials in Iran

Mexico1 site

  • Insituto Nacional de Cancerología

    Mexico City

Other trials in Mexico

Paraguay1 site

  • Instituto Privado de Hematologia e Investigaciona Clinica

    Asunción

Other trials in Paraguay

About this study

Official title: A Randomized, Double-blind, Phase III Study Comparing Biosimilar Rituximab (RTXM83) Plus CHOP Chemotherapy Versus a Reference Rituximab Plus CHOP (R-CHOP) in Patients With Diffuse Large B-cell Lymphoma (DLBCL) Given as First Line

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.

Read the 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.

Being tested
RTXM83, Mabthera
Keywords
Non-Hodgkin Lymphoma, DLBCL, Diffuse large b-cell lymphoma
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RTXM83Biological

    Also called Rituximab Biosimilar

    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.

  • MabtheraBiological

    Also called Reference rituximab

    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.

Study groups in NCT02268045
Study groupRoleWhat they receive
RTXM83ExperimentalActive Ingredient: Rituximab (Biosimilar)
Receives: Biological: RTXM83
MabTheraActive comparatorActive Ingredient: Rituximab
Receives: Biological: Mabthera

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)

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

    Compare the pharmacokinetic (PK) parameter (AUC 0-∞) calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1) in a population PK model.

    For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%.

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

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

    Compare the PK parameter (AUC 0-∞) calculated from start of the first infusion until Day 21 of administration of Cycle 6 in a population PK model.

    For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%.

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

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

    Compare the PK parameter (Cmax) calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1) in a population PK model.

    For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (Cmax) falls completely within the range 80%-125%.

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

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

    Compare the PK parameter (Cmax) calculated from start of the first infusion until Day 21 of administration of Cycle 6 in a population PK model.

    For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%.

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

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

    CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+.

    To compare the percent Change From Baseline ((Cycle 1 pre-dose) in pharmacodynamic markers (CD19+ and CD20+ Cells) in Peripheral Blood achieved in RTXM83 and Mabthera® arms at Cycle 1 end of infusion (EOI), 6 months and 9 months after last dose of treatment.

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

  6. Comparable Safety Profile in Both Treatment Arms

    Compare the frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) reported in each treatment arm.

    Measured: Up to FU3; 9 months after last dose of treatment

  7. Comparable Immunogenicity Profile Between RTXM83 and Mabthera®

    Anti-Drug Antibody (ADA) developed de novo (seroconversion) after 6 cycles of treatment and 9 months of follow-up.

    Measured: Up to FU3; 9 months after last dose of treatment

  8. Event Free Survival (EFS) in RTXM83 Arm and Mabthera® Arm

    Time from randomization to any of the following events: progressive disease, no achievement of CR, PR associated with treatment in excess of that per protocol, SD, relapse after achievement of CR, or death from any cause, whichever comes first.

    Measured: Up to FU3; 9 months after last dose of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2014 (estimated)
  2. Study startMay 2013
  3. Primary completionMay 2016
  4. Study completionJul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
272 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02268045
Sponsor's protocol ID
RTXM83-AC-01-11
Status last verified
Aug 2019
First submitted
19 Sep 2014
Last updated
26 Sep 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RTXM83 and Mabthera in people with Diffuse Large B-cell Lymphoma, run by mAbxience Research S.L. at 87 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 87 sites in Brazil, Argentina, Russia, India, Philippines and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Tumor response assessed after Cycle 6 or at the end of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02268045.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2019; AzTrials last refreshed its copy on 26 Oct 2026.

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