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

Phase 3

Completed

• Conditions: Nodal Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Follicular Non-Hodgkin's Lymphoma
• Interventions: Biological: rituximab

• Registration Number: NCT01701232
• Lead Sponsor: Biocad

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2012-10-03
• Study First Submitted QC: 2012-10-03
• Study First Posted: 2012-10-05
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-02
• Last Update Posted: 2017-11-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 174

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MabThera	rituximab	Reference rituximab at a dose of 375 mg/m2 intravenously once a week for four weeks (on days 1, 8, 15 and 22)
BCD-020	rituximab	Proposed rituximab biosimilar at a dose of 375 mg/m2 intravenously once a week for four weeks (on days 1, 8, 15 and 22)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (62)

HCG Bangalore Institute of Oncology; 🇮🇳 Bangalore, India

Acharya Tulasi Regional Cancer Treatment and Research Centre; 🇮🇳 Bikaner, India

Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute; 🇮🇳 Hyderabad, India

Public health facility "Irkutsk Regional Oncology Center"; 🇷🇺 Irkutsk, Russian Federation

State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic; 🇷🇺 Izhevsk, Russian Federation

Research Center for Hematology MHSD RF; 🇷🇺 Moscow, Russian Federation

Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation; 🇷🇺 Obninsk, Russian Federation

V.A. Baranov Republican Hospital of Ministry of Health republic Karelia; 🇷🇺 Petrozavodsk, Russian Federation

Official body of the health of the city of Moscow "Moscow City Clinical Hospital named after S. P. Botkin"; 🇷🇺 Moscow, Russian Federation

Regional government health care "Oryol Regional Hospital"; 🇷🇺 Oryol, Russian Federation

Saint Petersburg Pavlov State Medical University; 🇷🇺 Saint Petersburg, Russian Federation

Russian scientific center of radiology and surgery technologies; 🇷🇺 St.Petersburg, Russian Federation

Tula Regional Hospital; 🇷🇺 Tula, Russian Federation

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

Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan; 🇷🇺 Ufa, Russian Federation

Khmel'nyts'kyy Regional Hospital, Hematology Department; 🇺🇦 Khmel'nyts'kyy, Ukraine

National Cancer Institute of Ukraine, Oncohematology Department; 🇺🇦 Kiev, Ukraine

Omega Hospitals; 🇮🇳 Hyderabad, India

Fundación Reina Isabel; 🇨🇴 Cali, Colombia

Department of Medicine (Haemotology), St.John's Medical College Hospital; 🇮🇳 Bangalore, India

All India Institute of medical Sciences (AIIMS); 🇮🇳 Bhubaneswar, India

Medical Oncology Department, The Karnatak Cancer Therapy and Research Institute; 🇮🇳 Hubli, India

BIBI General hospital & cancer center; 🇮🇳 Hyderabad, India

City Cancer Center; 🇮🇳 Vijayawada, India

Municipal Institution "Central City Hospital № 7"; 🇷🇺 Ekaterinburg, Russian Federation

Arkhangelsk District Clinical Oncology Dispensary; 🇷🇺 Arkhangelsk, Russian Federation

City Hospital N8; 🇷🇺 Barnaul, Russian Federation

Clinical Oncology Dispensary N1; 🇷🇺 Krasnodar, Russian Federation

Public health facility "Lipetsk Regional Oncology Center"; 🇷🇺 Lipetsk, Russian Federation

N.N. Burdenko General Military Clinical Hospital; 🇷🇺 Moscow, Russian Federation

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

Public health facility "Kursk Regional Cancer Center," Health Committee of Kursk region; 🇷🇺 Kursk, Russian Federation

Perm Region Oncology Dispensary; 🇷🇺 Perm, Russian Federation

Pyatigorsk Oncology Center; 🇷🇺 Pyatigorsk, Russian Federation

Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency; 🇷🇺 Saint Petersburg, Russian Federation

St. Petersburg State Health Care Institution "Alexander City Hospital"; 🇷🇺 Saint Petersburg, Russian Federation

The federal government military educational institution of higher education, "Military Medical Academy named after SM Kirov's' Ministry of Defense"; 🇷🇺 Saint Petersurg, Russian Federation

Provincial health official body "Smolensk Regional Clinical Oncological Dispensary"; 🇷🇺 Smolensk, Russian Federation

Oncology Dispensary 2; 🇷🇺 Sochi, Russian Federation

Tambov Regional Oncology Center; 🇷🇺 Tambov, Russian Federation

Hospital Pablo Tobon Uribe; 🇨🇴 Medellín, Colombia

Sujan Surgicals; 🇮🇳 Amaravati, India

Nilratan Siracar Medical College & Hospital; 🇮🇳 Kolkata, India

King George Medical University; 🇮🇳 Lucknow, India

Department of Medical Oncology, Navneet Memorial Hospital, "Sushrusha"; 🇮🇳 Ahmedabad, India

HCG Multi Specialty Hospitals; 🇮🇳 Ahmedabad, India

Instituto Nacional de Cancerología; 🇨🇴 Bogotá, Colombia

Narayana Hrudayalaya Hospitals; 🇮🇳 Bangalore, India

Srinivasam Cancer Care Hospital; 🇮🇳 Bangalore, India

G.Kuppuswamy Naidu Memorial Hospital; 🇮🇳 Coimbatore, India

Department of Radiation Oncology, Meenakshi Mission Hospital & Research Centre; 🇮🇳 Madurai, India

Manas Super Speciality Hospital; 🇮🇳 Nashik, India

Municipal Health "Clinical Hospital № 5" Togliatti; 🇷🇺 Togliatti, Russian Federation

Public health care setting of the Tyumen region "Regional Oncology Center"; 🇷🇺 Tyumen, Russian Federation

State Institution "Institute of Blood Pathology and Transfusion Medicine AMS of Ukraine", Hematology Department; 🇺🇦 L'viv, Ukraine

Ivanovo Regional Oncology Center; 🇷🇺 Ivanovo, Russian Federation

Public health facility "Kemerovo Regional Hospital"; 🇷🇺 Kemerovo, Russian Federation

Saint Petersburg City Clinical Oncology Center; 🇷🇺 Saint Petersburg, Russian Federation

State Health Care Institution Republican Clinical Hospital named after G. G. Kuvatova; 🇷🇺 Ufa, Russian Federation

Volgograd District Oncology Dispensary №1; 🇷🇺 Volgograd, Russian Federation

N.N.Petrov Oncology Research Center; 🇷🇺 St.Petersburg, Russian Federation

Medi-Clinic Vereeniging; 🇿🇦 Vereeniging, South Africa