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

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.

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.