Follicular Non-Hodgkin's Lymphoma, Nodal Marginal Zone Lymphoma, Splenic Marginal Zone Lymphoma
Conditions
Keywords
lymphoma, non-Hodgkin's
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.
Interventions
BIOLOGICALrituximab
Patients will receive rituximab at a dose of 375 mg/m2 intravenously once a week for 4 weeks (on day 1,8,15,22)
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Colombia, India, Russia, South Africa, Ukraine
Outcome results
None listed