Clinical trial NCT01701232: Safety and Efficacy Study of BCD-020 in Therapy of Indolent Non-Hodgkin's Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Follicular Non-Hodgkin's Lymphoma
Nodal Marginal Zone Lymphoma
Splenic Marginal Zone Lymphoma
Keywords: lymphoma, non-Hodgkin's
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2012-10-05
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate
timeFrame: day 50 (cycle 4)
measure: CD20-positive cells count
timeFrame: day 50
Secondary outcomes:
measure: Cmax
timeFrame: day 22
measure: AUC(0-168)
timeFrame: 168 hours
measure: Complete response rate
timeFrame: day 50
measure: Frequency of AEs/sAEs grade 3-4 (CTCAE v.4.03)
timeFrame: day 50
measure: Levels of binding and neutralizing antibodies to rituximab
timeFrame: day 50
measure: AUC(0-1176), AUC(0-inf)
timeFrame: day 50
Other outcomes:
Locations:
city: Bogotá
country: Colombia
facility: Instituto Nacional de Cancerología
city: Cali
country: Colombia
facility: Fundación Reina Isabel
city: Medellín
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Ahmedabad
country: India
facility: HCG Multi Specialty Hospitals
city: Ahmedabad
country: India
facility: Department of Medical Oncology, Navneet Memorial Hospital, "Sushrusha"
city: Amaravati
country: India
facility: Sujan Surgicals
city: Bangalore
country: India
facility: HCG Bangalore Institute of Oncology
city: Bangalore
country: India
facility: Department of Medicine (Haemotology), St.John's Medical College Hospital
city: Bangalore
country: India
facility: Narayana Hrudayalaya Hospitals
city: Bangalore
country: India
facility: Srinivasam Cancer Care Hospital
city: Bhubaneswar
country: India
facility: All India Institute of medical Sciences (AIIMS)
city: Bikaner
country: India
facility: Acharya Tulasi Regional Cancer Treatment and Research Centre
city: Coimbatore
country: India
facility: G.Kuppuswamy Naidu Memorial Hospital
city: Hubli
country: India
facility: Medical Oncology Department, The Karnatak Cancer Therapy and Research Institute
city: Hyderabad
country: India
facility: BIBI General hospital & cancer center
city: Hyderabad
country: India
facility: Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute
city: Hyderabad
country: India
facility: Omega Hospitals
city: Kolkata
country: India
facility: Nilratan Siracar Medical College & Hospital
city: Lucknow
country: India
facility: King George Medical University
city: Madurai
country: India
facility: Department of Radiation Oncology, Meenakshi Mission Hospital & Research Centre
city: Nashik
country: India
facility: Manas Super Speciality Hospital
city: Vijayawada
country: India
facility: City Cancer Center
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk District Clinical Oncology Dispensary
city: Barnaul
country: Russian Federation
facility: City Hospital N8
city: Ekaterinburg
country: Russian Federation
facility: Municipal Institution "Central City Hospital № 7"
city: Irkutsk
country: Russian Federation
facility: Public health facility "Irkutsk Regional Oncology Center"
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Center
city: Izhevsk
country: Russian Federation
facility: State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic
city: Kemerovo
country: Russian Federation
facility: Public health facility "Kemerovo Regional Hospital"
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Dispensary N1
city: Kursk
country: Russian Federation
facility: Public health facility "Kursk Regional Cancer Center," Health Committee of Kursk region
city: Lipetsk
country: Russian Federation
facility: Public health facility "Lipetsk Regional Oncology Center"
city: Moscow
country: Russian Federation
facility: N.N. Burdenko General Military Clinical Hospital
city: Moscow
country: Russian Federation
facility: Russian Medical Academy of Post-Graduate Education, Ministry of Health and Social Development of the Russian Federation
city: Moscow
country: Russian Federation
facility: Research Center for Hematology MHSD RF
city: Moscow
country: Russian Federation
facility: Official body of the health of the city of Moscow "Moscow City Clinical Hospital named after S. P. Botkin"
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center, Ministry of Health and Social Development of the Russian Federation
city: Oryol
country: Russian Federation
facility: Regional government health care "Oryol Regional Hospital"
city: Perm
country: Russian Federation
facility: Perm Region Oncology Dispensary
city: Petrozavodsk
country: Russian Federation
facility: V.A. Baranov Republican Hospital of Ministry of Health republic Karelia
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Transfusiology Federal State Institution of Federal Medical and Biological Agency
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Health Care Institution "Alexander City Hospital"
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg City Clinical Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg Pavlov State Medical University
city: Saint Petersburg
country: Russian Federation
facility: V.A. Almazov Federal Center for Heart, Blood and Endocrinology, Ministry of Health and Social Development of the Russian Federation
city: Saint Petersurg
country: Russian Federation
facility: The federal government military educational institution of higher education, "Military Medical Academy named after SM Kirov's' Ministry of Defense"
city: Smolensk
country: Russian Federation
facility: Provincial health official body "Smolensk Regional Clinical Oncological Dispensary"
city: Sochi
country: Russian Federation
facility: Oncology Dispensary 2
city: St.Petersburg
country: Russian Federation
facility: N.N.Petrov Oncology Research Center
city: St.Petersburg
country: Russian Federation
facility: Russian scientific center of radiology and surgery technologies
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncology Center
city: Togliatti
country: Russian Federation
facility: Municipal Health "Clinical Hospital № 5" Togliatti
city: Tula
country: Russian Federation
facility: Tula Regional Hospital
city: Tyumen
country: Russian Federation
facility: Public health care setting of the Tyumen region "Regional Oncology Center"
city: Ufa
country: Russian Federation
facility: State Health Care Institution Republican Clinical Hospital named after G. G. Kuvatova
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan
city: Volgograd
country: Russian Federation
facility: Volgograd District Oncology Dispensary №1
city: Vereeniging
country: South Africa
facility: Medi-Clinic Vereeniging
city: Khmel'nyts'kyy
country: Ukraine
facility: Khmel'nyts'kyy Regional Hospital, Hematology Department
city: Kiev
country: Ukraine
facility: National Cancer Institute of Ukraine, Oncohematology Department
city: L'viv
country: Ukraine
facility: State Institution "Institute of Blood Pathology and Transfusion Medicine AMS of Ukraine", Hematology Department
Study officials:
affiliation: CJSC Biocad
name: Roman Ivanov, PhD,MD
role: STUDY_DIRECTOR
References: