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

NCT01701232 | Completed Phase 3

• 1 other identifier: BIORIX (BCD-020-3)
• Study Type: interventional
• Target: 174
• Locations: 5 countries
• Sites: 62

Brief Summary

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.

Conditions

Follicular Non-Hodgkin's Lymphoma; Nodal Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma

Keywords

lymphoma, non-Hodgkin's

Outcome Measures

Primary Outcomes (2)

• Overall response rate

  Estimation of the overall response rate in each treatment arm at the end of treatment

  day 50 (cycle 4)

• CD20-positive cells count

  Comparison of peripheral blood B-cell depletion and repletion after BCD-020 and MabThera intravenous administration

  day 50

Secondary Outcomes (6)

• Cmax

  day 22

• AUC(0-168)

  168 hours

• Complete response rate

  day 50

• Frequency of AEs/sAEs grade 3-4 (CTCAE v.4.03)

  day 50

• Levels of binding and neutralizing antibodies to rituximab

  day 50

Study Arms (2)

MabThera

ACTIVE COMPARATOR

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

BCD-020

EXPERIMENTAL

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

Interventions

rituximab BIOLOGICAL

Patients will receive rituximab at a dose of 375 mg/m2 intravenously once a week for 4 weeks (on day 1,8,15,22)

Also known as: Biological: BCD-020, MabThera

BCD-020; MabThera

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• Biocad: lead

Study Sites (62)

Instituto Nacional de Cancerología

Bogotá, Colombia

Location

Fundación Reina Isabel

Cali, Colombia

Location

Hospital Pablo Tobon Uribe

Medellín, Colombia

Location

HCG Multi Specialty Hospitals

Ahmedabad, 380006, India

Location

Department of Medical Oncology, Navneet Memorial Hospital, "Sushrusha"

Ahmedabad, 380009, India

Location

Sujan Surgicals

Amaravati, India

Location

HCG Bangalore Institute of Oncology

Bangalore, 560027, India

Location

Department of Medicine (Haemotology), St.John's Medical College Hospital

Bangalore, 560034, India

Location

Narayana Hrudayalaya Hospitals

Bangalore, 560099, India

Location

Srinivasam Cancer Care Hospital

Bangalore, India

Location

All India Institute of medical Sciences (AIIMS)

Bhubaneswar, India

Location

Acharya Tulasi Regional Cancer Treatment and Research Centre

Bikaner, India

Location

G.Kuppuswamy Naidu Memorial Hospital

Coimbatore, 641037, India

Location

Medical Oncology Department, The Karnatak Cancer Therapy and Research Institute

Hubli, 580025, India

Location

BIBI General hospital & cancer center

Hyderabad, 500024, India

Location

Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute

Hyderabad, 500034, India

Location

Omega Hospitals

Hyderabad, 500034, India

Location

Nilratan Siracar Medical College & Hospital

Kolkata, India

Location

King George Medical University

Lucknow, India

Location

Department of Radiation Oncology, Meenakshi Mission Hospital & Research Centre

Madurai, 625107, India

Location

Manas Super Speciality Hospital

Nashik, India

Location

City Cancer Center

Vijayawada, India

Location

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, 163045, Russia

Location

City Hospital N8

Barnaul, 656010, Russia

Location

Public health facility "Irkutsk Regional Oncology Center"

Irkutsk, 664035, Russia

Location

Ivanovo Regional Oncology Center

Ivanovo, 153013, Russia

Location

State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic

Izhevsk, 426009, Russia

Location

Public health facility "Kemerovo Regional Hospital"

Kemerovo, 650066, Russia

Location

Clinical Oncology Dispensary N1

Krasnodar, 350040, Russia

Location

Public health facility "Kursk Regional Cancer Center," Health Committee of Kursk region

Kursk, 305035, Russia

Location

Public health facility "Lipetsk Regional Oncology Center"

Lipetsk, 398005, Russia

Location

N.N. Burdenko General Military Clinical Hospital

Moscow, 105229, Russia

Location

Russian Medical Academy of Post-Graduate Education, Ministry of Health and Social Development of the Russian Federation

Moscow, 123995, Russia

Location

Research Center for Hematology MHSD RF

Moscow, 125167, Russia

Location

Official body of the health of the city of Moscow "Moscow City Clinical Hospital named after S. P. Botkin"

Moscow, 125284, Russia

Location

Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation

Obninsk, 249036, Russia

Location

Regional government health care "Oryol Regional Hospital"

Oryol, 302028, Russia

Location

Perm Region Oncology Dispensary

Perm, 614066, Russia

Location

V.A. Baranov Republican Hospital of Ministry of Health republic Karelia

Petrozavodsk, 185000, Russia

Location

Pyatigorsk Oncology Center

Pyatigorsk, 357502, Russia

Location

Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency

Saint Petersburg, 191024, Russia

Location

St. Petersburg State Health Care Institution "Alexander City Hospital"

Saint Petersburg, 193312, Russia

Location

Saint Petersburg City Clinical Oncology Center

Saint Petersburg, 197022, Russia

Location

Saint Petersburg Pavlov State Medical University

Saint Petersburg, 197022, Russia

Location

V.A. Almazov Federal Center for Heart, Blood and Endocrinology, Ministry of Health and Social Development of the Russian Federation

Saint Petersburg, 197341, Russia

Location

N.N.Petrov Oncology Research Center

Saint Petersburg, 197758, Russia

Location

Russian scientific center of radiology and surgery technologies

Saint Petersburg, Russia

Location

The federal government military educational institution of higher education, "Military Medical Academy named after SM Kirov's' Ministry of Defense"

Saint Petersurg, 194044, Russia

Location

Provincial health official body "Smolensk Regional Clinical Oncological Dispensary"

Smolensk, 214000, Russia

Location

Oncology Dispensary 2

Sochi, 354057, Russia

Location

Tambov Regional Oncology Center

Tambov, 390013, Russia

Location

Municipal Health "Clinical Hospital № 5" Togliatti

Tolyatti, 445846, Russia

Location

Tula Regional Hospital

Tula, 300053, Russia

Location

Public health care setting of the Tyumen region "Regional Oncology Center"

Tyumen, 625041, Russia

Location

State Health Care Institution Republican Clinical Hospital named after G. G. Kuvatova

Ufa, 450005, Russia

Location

Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan

Ufa, 450054, Russia

Location

Volgograd District Oncology Dispensary №1

Volgograd, 400138, Russia

Location

Municipal Institution "Central City Hospital № 7"

Yekaterinburg, 620137, Russia

Location

Medi-Clinic Vereeniging

Vereeniging, South Africa

Location

Khmel'nyts'kyy Regional Hospital, Hematology Department

Khmelnytskyi, 29000, Ukraine

Location

National Cancer Institute of Ukraine, Oncohematology Department

Kiev, 03022, Ukraine

Location

State Institution "Institute of Blood Pathology and Transfusion Medicine AMS of Ukraine", Hematology Department

Lviv, 79044, Ukraine

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin

Interventions

Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roman Ivanov, PhD,MD

  CJSC Biocad

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2012
• First Posted: October 5, 2012
• Study Start: September 1, 2011
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

UA (3); CO (3); IN (19); RU (36); ZA (1)