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

Splenic Marginal Zone Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01701232
• Other study ID #: BIORIX (BCD-020-3)
• Status: Completed
• Phase: Phase 3
• First received: October 3, 2012
• Last updated: November 2, 2017
• Start date: September 2011
• Est. completion date: January 2017

Study information

• Verified date: November 2017
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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 ??? 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.

Related Conditions & MeSH terms

• Follicular Non-Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin
• Nodal Marginal Zone Lymphoma
• Splenic Marginal Zone Lymphoma

Intervention

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)

Locations

Country	Name	City	State
Colombia	Instituto Nacional de Cancerología	Bogotá
Colombia	Fundación Reina Isabel	Cali
Colombia	Hospital Pablo Tobon Uribe	Medellín
India	Department of Medical Oncology, Navneet Memorial Hospital, "Sushrusha"	Ahmedabad
India	HCG Multi Specialty Hospitals	Ahmedabad
India	Sujan Surgicals	Amaravati
India	Department of Medicine (Haemotology), St.John's Medical College Hospital	Bangalore
India	HCG Bangalore Institute of Oncology	Bangalore
India	Narayana Hrudayalaya Hospitals	Bangalore
India	Srinivasam Cancer Care Hospital	Bangalore
India	All India Institute of medical Sciences (AIIMS)	Bhubaneswar
India	Acharya Tulasi Regional Cancer Treatment and Research Centre	Bikaner
India	G.Kuppuswamy Naidu Memorial Hospital	Coimbatore
India	Medical Oncology Department, The Karnatak Cancer Therapy and Research Institute	Hubli
India	BIBI General hospital & cancer center	Hyderabad
India	Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute	Hyderabad
India	Omega Hospitals	Hyderabad
India	Nilratan Siracar Medical College & Hospital	Kolkata
India	King George Medical University	Lucknow
India	Department of Radiation Oncology, Meenakshi Mission Hospital & Research Centre	Madurai
India	Manas Super Speciality Hospital	Nashik
India	City Cancer Center	Vijayawada
Russian Federation	Arkhangelsk District Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	City Hospital N8	Barnaul
Russian Federation	Municipal Institution "Central City Hospital ? 7"	Ekaterinburg
Russian Federation	Public health facility "Irkutsk Regional Oncology Center"	Irkutsk
Russian Federation	Ivanovo Regional Oncology Center	Ivanovo
Russian Federation	State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic	Izhevsk
Russian Federation	Public health facility "Kemerovo Regional Hospital"	Kemerovo
Russian Federation	Clinical Oncology Dispensary N1	Krasnodar
Russian Federation	Public health facility "Kursk Regional Cancer Center," Health Committee of Kursk region	Kursk
Russian Federation	Public health facility "Lipetsk Regional Oncology Center"	Lipetsk
Russian Federation	N.N. Burdenko General Military Clinical Hospital	Moscow
Russian Federation	Official body of the health of the city of Moscow "Moscow City Clinical Hospital named after S. P. Botkin"	Moscow
Russian Federation	Research Center for Hematology MHSD RF	Moscow
Russian Federation	Russian Medical Academy of Post-Graduate Education, Ministry of Health and Social Development of the Russian Federation	Moscow
Russian Federation	Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation	Obninsk
Russian Federation	Regional government health care "Oryol Regional Hospital"	Oryol
Russian Federation	Perm Region Oncology Dispensary	Perm
Russian Federation	V.A. Baranov Republican Hospital of Ministry of Health republic Karelia	Petrozavodsk
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	Saint Petersburg City Clinical Oncology Center	Saint Petersburg
Russian Federation	Saint Petersburg Pavlov State Medical University	Saint Petersburg
Russian Federation	St. Petersburg State Health Care Institution "Alexander City Hospital"	Saint Petersburg
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	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	N.N.Petrov Oncology Research Center	St.Petersburg
Russian Federation	Russian scientific center of radiology and surgery technologies	St.Petersburg
Russian Federation	Tambov Regional Oncology Center	Tambov
Russian Federation	Municipal Health "Clinical Hospital ? 5" Togliatti	Togliatti
Russian Federation	Tula Regional Hospital	Tula
Russian Federation	Public health care setting of the Tyumen region "Regional Oncology Center"	Tyumen
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan	Ufa
Russian Federation	State Health Care Institution Republican Clinical Hospital named after G. G. Kuvatova	Ufa
Russian Federation	Volgograd District Oncology Dispensary ?1	Volgograd
South Africa	Medi-Clinic Vereeniging	Vereeniging
Ukraine	Khmel'nyts'kyy Regional Hospital, Hematology Department	Khmel'nyts'kyy
Ukraine	National Cancer Institute of Ukraine, Oncohematology Department	Kiev
Ukraine	State Institution "Institute of Blood Pathology and Transfusion Medicine AMS of Ukraine", Hematology Department	L'viv

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Colombia,  India,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Estimation of the overall response rate in each treatment arm at the end of treatment	day 50 (cycle 4)
Primary	CD20-positive cells count	Comparison of peripheral blood B-cell depletion and repletion after BCD-020 and MabThera intravenous administration	day 50
Secondary	Cmax	Estimation of maximum rituximab serum concentrations after administration of BCD-020 to that obtained after administration of MabThera	day 22
Secondary	AUC(0-168)	Estimation of rituximab exposition after administration of BCD-020 to that obtained after administration of MabThera	168 hours
Secondary	Complete response rate	Assessment of complete response rates of BCD-020 and MabThera given as a monotherapy at the end/completion of the treatment	day 50
Secondary	Frequency of AEs/sAEs grade 3-4 (CTCAE v.4.03)	Evaluation of the safety profiles of BCD-020 and MabThera	day 50
Secondary	Levels of binding and neutralizing antibodies to rituximab	Immunogenicity assessment of BCD-020 and MabThera	day 50
Secondary	AUC(0-1176), AUC(0-inf)	Estimation of rituximab serum concentrations after administration of BCD-020 to that obtained after administration of MabThera	day 50

External Links

•   Biocad official website