Safety and Efficacy Study of BCD-020 in Therapy of Indolent Non-Hodgkin's Lymphoma

November 2, 2017 updated by: Biocad

A Multicenter Open-label Randomized Study of BCD-020 (Rituximab, CJSC BIOCAD, Russia) Efficacy and Safety in Comparison With MabThera (F. Hoffmann-La Roche Ltd., Switzerland) in Monotherapy of CD20-positive Indolent Non-Hodgkin's Lymphoma

This international multi-center, randomized, controlled, open-label study investigated the pharmacokinetics, pharmacodynamics, efficacy and safety of BCD-020 (INN: rituximab, CJSC Biocad) versus MabThera® (INN: rituximab, F. Hoffmann La Roche, Ltd.) both administered as a monotherapy of patients with indolent non-Hodgkin's lymphoma.

Patients were randomized to receive 375 mg/m² BCD-020 as intravenous infusion once a week for 4 weeks or MabThera® at the same regimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

174

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Colombia
      • Bogotá, Colombia
        • Instituto Nacional De Cancerologia
      • Cali, Colombia
        • Fundación Reina Isabel
      • Medellín, Colombia
        • Hospital Pablo Tobon Uribe
  • India
      • Ahmedabad, India, 380006
        • HCG Multi Specialty Hospitals
      • Ahmedabad, India, 380009
        • Department of Medical Oncology, Navneet Memorial Hospital, "Sushrusha"
      • Amaravati, India
        • Sujan Surgicals
      • Bangalore, India, 560027
        • HCG Bangalore Institute of Oncology
      • Bangalore, India, 560099
        • Narayana Hrudayalaya Hospitals
      • Bangalore, India
        • Srinivasam Cancer Care Hospital
      • Bangalore, India, 560034
        • Department of Medicine (Haemotology), St.John's Medical College Hospital
      • Bhubaneswar, India
        • All India Institute Of Medical Sciences (AIIMS)
      • Bikaner, India
        • Acharya Tulasi Regional Cancer Treatment and Research Centre
      • Coimbatore, India, 641037
        • G.Kuppuswamy Naidu Memorial Hospital
      • Hubli, India, 580025
        • Medical Oncology Department, The Karnatak Cancer Therapy and Research Institute
      • Hyderabad, India, 500024
        • BIBI General hospital & cancer center
      • Hyderabad, India, 500034
        • Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute
      • Hyderabad, India, 500034
        • Omega Hospitals
      • Kolkata, India
        • Nilratan Siracar Medical College & Hospital
      • Lucknow, India
        • King George Medical University
      • Madurai, India, 625107
        • Department of Radiation Oncology, Meenakshi Mission Hospital & Research Centre
      • Nashik, India
        • Manas Super Speciality Hospital
      • Vijayawada, India
        • City Cancer Center
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163045
        • Arkhangelsk District Clinical Oncology Dispensary
      • Barnaul, Russian Federation, 656010
        • City Hospital N8
      • Ekaterinburg, Russian Federation, 620137
        • Municipal Institution "Central City Hospital № 7"
      • Irkutsk, Russian Federation, 664035
        • Public health facility "Irkutsk Regional Oncology Center"
      • Ivanovo, Russian Federation, 153013
        • Ivanovo Regional Oncology Center
      • Izhevsk, Russian Federation, 426009
        • State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic
      • Kemerovo, Russian Federation, 650066
        • Public health facility "Kemerovo Regional Hospital"
      • Krasnodar, Russian Federation, 350040
        • Clinical Oncology Dispensary N1
      • Kursk, Russian Federation, 305035
        • Public health facility "Kursk Regional Cancer Center," Health Committee of Kursk region
      • Lipetsk, Russian Federation, 398005
        • Public health facility "Lipetsk Regional Oncology Center"
      • Moscow, Russian Federation, 105229
        • N.N. Burdenko General Military Clinical Hospital
      • Moscow, Russian Federation, 123995
        • Russian Medical Academy of Post-Graduate Education, Ministry of Health and Social Development of the Russian Federation
      • Moscow, Russian Federation, 125167
        • Research Center for Hematology MHSD RF
      • Moscow, Russian Federation, 125284
        • Official body of the health of the city of Moscow "Moscow City Clinical Hospital named after S. P. Botkin"
      • Obninsk, Russian Federation, 249036
        • Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation
      • Oryol, Russian Federation, 302028
        • Regional government health care "Oryol Regional Hospital"
      • Perm, Russian Federation, 614066
        • Perm Region Oncology Dispensary
      • Petrozavodsk, Russian Federation, 185000
        • V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
      • Pyatigorsk, Russian Federation, 357502
        • Pyatigorsk Oncology Center
      • Saint Petersburg, Russian Federation, 197022
        • Saint Petersburg City Clinical Oncology Center
      • Saint Petersburg, Russian Federation, 191024
        • Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency
      • Saint Petersburg, Russian Federation, 193312
        • St. Petersburg State Health Care Institution "Alexander City Hospital"
      • Saint Petersburg, Russian Federation, 197022
        • Saint Petersburg Pavlov State Medical University
      • Saint Petersburg, Russian Federation, 197341
        • V.A. Almazov Federal Center for Heart, Blood and Endocrinology, Ministry of Health and Social Development of the Russian Federation
      • Saint Petersurg, Russian Federation, 194044
        • The federal government military educational institution of higher education, "Military Medical Academy named after SM Kirov's' Ministry of Defense"
      • Smolensk, Russian Federation, 214000
        • Provincial health official body "Smolensk Regional Clinical Oncological Dispensary"
      • Sochi, Russian Federation, 354057
        • Oncology Dispensary 2
      • St.Petersburg, Russian Federation, 197758
        • N.N.Petrov Oncology Research Center
      • St.Petersburg, Russian Federation
        • Russian scientific center of radiology and surgery technologies
      • Tambov, Russian Federation, 390013
        • Tambov Regional Oncology Center
      • Togliatti, Russian Federation, 445846
        • Municipal Health "Clinical Hospital № 5" Togliatti
      • Tula, Russian Federation, 300053
        • Tula Regional Hospital
      • Tyumen, Russian Federation, 625041
        • Public health care setting of the Tyumen region "Regional Oncology Center"
      • Ufa, Russian Federation, 450054
        • Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan
      • Ufa, Russian Federation, 450005
        • State Health Care Institution Republican Clinical Hospital named after G. G. Kuvatova
      • Volgograd, Russian Federation, 400138
        • Volgograd District Oncology Dispensary №1
  • South Africa
      • Vereeniging, South Africa
        • Medi-Clinic Vereeniging
  • Ukraine
      • Khmel'nyts'kyy, Ukraine, 29000
        • Khmel'nyts'kyy Regional Hospital, Hematology Department
      • Kiev, Ukraine, 03022
        • National Cancer Institute of Ukraine, Oncohematology Department
      • L'viv, Ukraine, 79044
        • State Institution "Institute of Blood Pathology and Transfusion Medicine AMS of Ukraine", Hematology Department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Having signed a written informed consent;
  • Patients' age is 18 years or more;
  • Diagnosis of CD20-positive indolent non-Hodgkin lymphoma of following morphological types:Follicular non-Hodgkin lymphoma stage II-IV according to Ann Arbor, grade I-II;Nodal marginal zone lymphoma stage II-IV according to Ann Arbor; Splenic marginal zone lymphoma.
  • Life expectancy of not less than 3 months after the enrollment in the study;
  • Morphological and immunohistochemical examination of the tumor (both lymph node biopsy and bone marrow biopsy) - within 3 months before the enrollment in the study ;
  • Performance status ≤2 on the ECOG scale;
  • Hemoglobin > 80 g/l; leukocyte count ≥ 3.0×109/l but less than 25×109/l, absolute neutrophil count ≥1.5×109/l, platelet count ≥100×109/l;
  • Presence of at least one measurable lesion;
  • Patient's ability in the investigator's opinion to comply with the protocol procedures;
  • Willingness of patients with preserved reproductive function to use reliable contraception methods (at least two contraception methods in women, e.g., spermicide and condom).

Exclusion Criteria:

  • Bulky disease - size of any single lesion more than 10 cm in the greatest diameter;
  • Secondary transformation to high-grade lymphoma;
  • Other types of non-Hodgkin lymphomas apart from follicular non-Hodgkin stage II-IV lymphoma according to Ann Arbor, grade 1,2; nodal marginal zone lymphoma stage II-IV according to Ann Arbor; splenic marginal zone lymphoma.
  • Patients regularly taking corticosteroids during 1 month preceding the enrollment in the study;
  • Occurrence of other (aside from NHL) diseases that can distort the assessment of the main disease symptoms expression; mask, enhance, modify the main disease symptoms or induce clinical and laboratory-instrumental symptoms similar to the non-Hodgkin lymphomas; Severe resistant hypertension; Decompensated forms of heart (NYHA class ХСН III, IV), liver and kidney disorders (creatinine level >133 µmol/l, AST, ALT, and bilirubin level 3 times exceeding the norm) except for the cases where the symptom is caused by lymphoma; Decompensated respiratory failure; Tumor infiltration of the lungs; Decompensated diabetes mellitus; Active autoimmune diseases; Ongoing infections requiring antimicrobial therapy.
  • Usage of the drugs:

At any time prior to the enrollment into the study - interferon-based drugs or monoclonal antibodies for the treatment of NHL; Chemotherapy or radiotherapy was completed less than 21 day prior to the enrollment into the study; Vaccination within 1 week prior to the enrollment into the study;

  • Presence of any psychiatric disorders including major depressive conditions and/or suicidal thoughts in anamnesis that in opinion of the investigator may put a patient at an excessive risk or influence the ability of patients to fulfill the study protocol;
  • Myocardial infarction less than 1 month before the enrollment into the study;
  • Severe CNS or PNS dysfunctions;
  • Drug and alcohol addiction;
  • Known HIV, HBV, HCV infection, syphilis;
  • Known primary or secondary immunodeficiency;
  • Primary CNS lymphoma or metastasis in the CNS;
  • Known intolerance or allergy to mouse proteins or any components of the study drugs, and also to the premedication drugs;
  • Pregnancy or lactation;
  • Prior or concomitant malignances except for adequately treated basal cell carcinoma and in situ cervical cancer;
  • Any restraints or impossibility to administer the study drug via an intravenous infusion;
  • Major surgery within 1 week prior to the enrollment into the study;
  • Simultaneous participation in any other clinical study or any preceding participation in other studies within 3 months prior to enrollment in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: MabThera
Reference rituximab at a dose of 375 mg/m2 intravenously once a week for four weeks (on days 1, 8, 15 and 22)
Biological: rituximab
Patients will receive rituximab at a dose of 375 mg/m2 intravenously once a week for 4 weeks (on day 1,8,15,22)
Other Names:
  • Biological: BCD-020, MabThera
Experimental: BCD-020
Proposed rituximab biosimilar at a dose of 375 mg/m2 intravenously once a week for four weeks (on days 1, 8, 15 and 22)
Biological: rituximab
Patients will receive rituximab at a dose of 375 mg/m2 intravenously once a week for 4 weeks (on day 1,8,15,22)
Other Names:
  • Biological: BCD-020, MabThera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: day 50 (cycle 4)
Estimation of the overall response rate in each treatment arm at the end of treatment
day 50 (cycle 4)
CD20-positive cells count
Time Frame: day 50
Comparison of peripheral blood B-cell depletion and repletion after BCD-020 and MabThera intravenous administration
day 50

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax
Time Frame: day 22
Estimation of maximum rituximab serum concentrations after administration of BCD-020 to that obtained after administration of MabThera
day 22
AUC(0-168)
Time Frame: 168 hours
Estimation of rituximab exposition after administration of BCD-020 to that obtained after administration of MabThera
168 hours
Complete response rate
Time Frame: day 50
Assessment of complete response rates of BCD-020 and MabThera given as a monotherapy at the end/completion of the treatment
day 50
Frequency of AEs/sAEs grade 3-4 (CTCAE v.4.03)
Time Frame: day 50
Evaluation of the safety profiles of BCD-020 and MabThera
day 50
Levels of binding and neutralizing antibodies to rituximab
Time Frame: day 50
Immunogenicity assessment of BCD-020 and MabThera
day 50
AUC(0-1176), AUC(0-inf)
Time Frame: day 50
Estimation of rituximab serum concentrations after administration of BCD-020 to that obtained after administration of MabThera
day 50

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biocad

Investigators

  • Study Director: Roman Ivanov, PhD,MD, CJSC Biocad

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

October 3, 2012

First Submitted That Met QC Criteria

October 3, 2012

First Posted (Estimate)

October 5, 2012

Study Record Updates

Last Update Posted (Actual)

November 6, 2017

Last Update Submitted That Met QC Criteria

November 2, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BIORIX (BCD-020-3)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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