Safety and Efficacy Study of BCD-020 in Therapy of Indolent Non-Hodgkin's Lymphoma
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 |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Having signed a written informed consent;
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Patients' age is 18 years or more;
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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.
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Life expectancy of not less than 3 months after the enrollment in the study;
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Morphological and immunohistochemical examination of the tumor (both lymph node biopsy and bone marrow biopsy) - within 3 months before the enrollment in the study ;
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Performance status ≤2 on the ECOG scale;
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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;
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Presence of at least one measurable lesion;
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Patient's ability in the investigator's opinion to comply with the protocol procedures;
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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:
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Bulky disease - size of any single lesion more than 10 cm in the greatest diameter;
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Secondary transformation to high-grade lymphoma;
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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.
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Patients regularly taking corticosteroids during 1 month preceding the enrollment in the study;
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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.
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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;
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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;
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Myocardial infarction less than 1 month before the enrollment into the study;
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Severe CNS or PNS dysfunctions;
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Drug and alcohol addiction;
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Known HIV, HBV, HCV infection, syphilis;
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Known primary or secondary immunodeficiency;
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Primary CNS lymphoma or metastasis in the CNS;
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Known intolerance or allergy to mouse proteins or any components of the study drugs, and also to the premedication drugs;
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Pregnancy or lactation;
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Prior or concomitant malignances except for adequately treated basal cell carcinoma and in situ cervical cancer;
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Any restraints or impossibility to administer the study drug via an intravenous infusion;
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Major surgery within 1 week prior to the enrollment into the study;
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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 | |
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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.- BIORIX (BCD-020-3)