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

Sponsor
Biocad (Industry)
Overall Status
Completed
CT.gov ID
NCT01701232
Collaborator
(none)
174
62
2
64
2.8
0

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: rituximab
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
174 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
Jan 1, 2017
Actual Study Completion Date :
Jan 1, 2017

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Overall response rate [day 50 (cycle 4)]

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

    2. 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

    1. Cmax [day 22]

      Estimation of maximum rituximab serum concentrations after administration of BCD-020 to that obtained after administration of MabThera

    2. AUC(0-168) [168 hours]

      Estimation of rituximab exposition after administration of BCD-020 to that obtained after administration of MabThera

    3. 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

    4. Frequency of AEs/sAEs grade 3-4 (CTCAE v.4.03) [day 50]

      Evaluation of the safety profiles of BCD-020 and MabThera

    5. Levels of binding and neutralizing antibodies to rituximab [day 50]

      Immunogenicity assessment of BCD-020 and MabThera

    6. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 95 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Biocad

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Biocad
    ClinicalTrials.gov Identifier:
    NCT01701232
    Other Study ID Numbers:
    • BIORIX (BCD-020-3)
    First Posted:
    Oct 5, 2012
    Last Update Posted:
    Nov 6, 2017
    Last Verified:
    Nov 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Biocad
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 6, 2017