MedPath

MabionCD20 Compared to MabThera in Lymphoma Patients

Phase 3
Completed
Conditions
Diffuse Large B-Cell Lymphoma
Interventions
Registration Number
NCT02617485
Lead Sponsor
Mabion SA
Brief Summary

The aim of the study is to demonstrate the high level of biosimilarity between MabionCD20 (MABION SA) and the reference product: MabThera (rituximab by Hoffman-La Roche) in patients with CD20-positive diffuse large B-cell lymphoma.

Detailed Description

Patients who meet criteria for participation in this study receive 8 intravenous infusions of MabionCD20® or MabThera® 21 days interval in combination with standard dosage regimen of CHOP. The duration of the study is 12 months. The treatment and observation period will last 26 weeks starting from Day 1, until Week 26 - one month after last IMP infusion.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
143
Inclusion Criteria
  1. Patients with histological confirmed CD20 (cluster of differentiation 20) positive diffuse large B cell lymphoma (DLBCL)
  2. Patients that had been diagnosed according to the WHO classification;
  3. Performance status ≤ 2 on the ECOG (Eastern Cooperative Oncology Group) / WHO (world Health Organization) scale, performance status of 3 will be accepted if impairment is caused by DLBCL complications and improvement is expected once therapy is initiated;
Exclusion Criteria
  1. Life expectance less than 6 months;
  2. Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment;
  3. Rituximab, other anti-CD20 mAb (Monoclonal Antibodies) drug treatment, treatment with any cell depleting therapies - e.g., anti-CD4 (cluster of differentiation 4) anti-CD5 (cluster of differentiation 5), anti-CD3 (cluster of differentiation 3), anti-CD19 (cluster of differentiation 19), anti CD11 (cluster of differentiation 11), anti-CD22 (cluster of differentiation 11), BLys/BAFF (B Lymphocyte Stimulator/B-cell activating factor) within 1,5 years before screening;

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MabionCD20CyclophosphamideA course of MabionCD20 consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabTheraVincristineA course of MabThera consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabionCD20VincristineA course of MabionCD20 consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabTheraprednisoneA course of MabThera consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabionCD20RituximabA course of MabionCD20 consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabionCD20DoxorubicinA course of MabionCD20 consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabionCD20prednisoneA course of MabionCD20 consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabTheraRituximabA course of MabThera consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabTheraDoxorubicinA course of MabThera consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
MabTheraCyclophosphamideA course of MabThera consists of intravenous infusions in dose 375 mg/m2 body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles. Intervention: Drug: Rituximab
Primary Outcome Measures
NameTimeMethod
Area Under the Serum Concentration-time Curve From Day 1 to Week 4 (AUC[1-4])Baseline to Week 4

Area under the serum concentration-time curve from time zero (Day 1) to final time point measured after the first administration (Week 1) until Week 4 (AUC(W1-W4)). PK blood samples for this endpoint were drawn at Day 1 (before and after the first infusion), Day 8 ± 1 (7 days after first infusion), Day 15 ± 1 (14 days after first infusion), Day 22 ± 2 (before and after completion of the second infusion).

Area Under the Serum Concentration-time Curve From Week 13 to Week 26 (AUC[W13-W26])Week 13 to Week 26

Area under the serum concentration-time curve from time zero to final time point measured from Week 13 until Week 26 (AUC\[W13-W26\]). PK blood samples for this endpoint were drawn at Day 85 ± 4 (before and after completion of the fifth infusion), Day 106 ± 4 (before and after completion of sixth infusion), Day 127 ± 4 (before and after completion of the seventh infusion), Day 148 ± 4 (before and after completion of the eight infusion), Day 155 ± 4 (one week after last infusion) and Day 176 ± 4 (one month after last infusion).

Secondary Outcome Measures
NameTimeMethod
Kel (Post 5th and 8th Infusions)Week 13 (5th infusion) and Week 22 (8th infusion)

Elimination Rate Constant at steady stade after the 5th and 8th infusions.

CLss (Post 5th and 8th Infusions)Week 13 to Week 16 and Week 22 to Week 26

Clearance at steady state after the 5th and 8th infusions.

Ctrough (Before 8th Infusion)Week 22

Trough serum concentration measured at the end of a dosing interval at steady state, taken directly before eighth infusion.

Efficacy Assessment at Week 26Week 26

An efficacy assessment was made after 8 treatment cycles (at Week 26) based on tumour responses classified according to the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas (Cheson et al. 1999). Response was assessed based on clinical, radiologic (CT scan) and pathologic (bone marrow) criteria. Possible efficacy responses were: complete response, partial response, stable disease, and progressive disease. Efficacy reported here includes all patients included in the ITT set.

Adverse Eventsfrom baseline to Week 46

Percentage of patients with at least one AE in a given category. Data from the entire follow-up are included (Period 1 and Period 2).

T1/2 (Post 5th and 8th Infusions)Week 13 to Week 16 and Week 22 to Week 26

Elimination half-life at steady state after the 5th and 8th infusions.

Cmax (Post 5th and 8th Infusion)Week 13 (5th infusion) and Week 22 (8th infusion)

Maximum serum drug concentration (Cmax) at steady state after the 5th and 8th infusions.

AUC (W1-W26)Week 1 until Week 26

Area under the serum concentration-time curve measured after the first administration (Week 1) until Week 26 (AUC(1-26))

AUC (W1-W26) B-cellbaseline to Week 26

Area under the serum concentration-time curve of CD19+ B cell counts, measured from the first administration to the final time point at Week 26 (AUC(1-26) B-cell).

Trial Locations

Locations (35)

Medulla - Chemotherapy and Immunotherapy Clinic

🇬🇪

Tbilisi, Georgia

GH "dr.Josip Bencevic"

🇭🇷

Slavonski Brod, Croatia

CHC Zagreb

🇭🇷

Zagreb, Croatia

Clinical Hospital Center Zvezdara

🇷🇸

Belgrade, Serbia

Szpital Wojewódzki w Opolu, Oddział Hematologii i Onkologii Hematologicznej

🇵🇱

Opole, Poland

Clinical Hospital Center Zemun

🇷🇸

Belgrade, Serbia

Regional Clinical Oncology Dispensary, Chemotherapy Department

🇺🇦

Ivano-Frankivsk, Ukraine

University Clinical Center Banja Luka

🇧🇦

Banja Luka, Bosnia and Herzegovina

HEMA

🇬🇪

Tbilisi, Georgia

CH Merkur

🇭🇷

Zagreb, Croatia

Institut of Oncology, Hematology Department

🇲🇩

Chisinau, Moldova, Republic of

Wojewódzki Szpital Specjalistyczny w Legnicy, Oddział Hematologiczny

🇵🇱

Legnica, Poland

Samodzielny Publiczny Szpital Kliniczny nr1, Klinika Hematologii i Transplantacji Szpiku

🇵🇱

Lublin, Poland

Military Hospital Academy

🇷🇸

Belgrade, Serbia

Regional clinical Hospital named after Novak, Hematology Department

🇺🇦

Uzhgorod, Ukraine

Vinnitsya Regional Clinical Oncology Dispensary, Chemotherapy Department,

🇺🇦

Vinnitsya, Ukraine

National Institute of Cancer, Department of chemotherapy

🇺🇦

Kiev, Ukraine

University Clinical Center Sarajevo

🇧🇦

Sarajevo, Bosnia and Herzegovina

Kiev City Clinical Oncological Center, Department of chemotherapy #2

🇺🇦

Kiev, Ukraine

Kryvyi Rih Oncology Dispensary, Dnipropetrovsk Highway

🇺🇦

Kryvyi Rih, Ukraine

General Hospital Zenica

🇧🇦

Zenica, Bosnia and Herzegovina

S. Khechinashvili state University clinic

🇬🇪

Tbilisi, Georgia

MTZ Clinical Research Sp. Z o.o.

🇵🇱

Warsaw, Poland

Regional Clinical Hospital of Ivano-Frankivsk, Hematology Department.

🇺🇦

Ivano-Frankivsk, Ukraine

Mykolayiv Region Clinical Hospital, Heamotology department

🇺🇦

Mykolayiv, Ukraine

Poltava regional oncology hospital, heamotherapy department

🇺🇦

Poltava, Ukraine

Regional Oncology dispensary

🇺🇦

Zaporizhzhia, Ukraine

University Clinical Center Tuzla

🇧🇦

Tuzla, Bosnia and Herzegovina

Municipal Institution "Dnipropetrovsk City multi-field Clinical Hospital #4", Oncology and medical radiology department

🇺🇦

Dnipropetrovsk, Ukraine

Kharkiv Regional Clinical Oncology Centre, Deartment of haematology

🇺🇦

Kharkiv, Ukraine

Public utility "Chernivtsi regional clinical oncology dispensary", Day patient department

🇺🇦

Chernivtsi, Ukraine

Utility Enterprise "Kirovograd regional oncology dispensary"

🇺🇦

Kirovohrad, Ukraine

Volyn' Regional clinical hospital, Haematology Department

🇺🇦

Lutsk, Ukraine

State institution "Institute for haemotopathology and haemotransfusion of National Academy of science of Ukraine

🇺🇦

Lviv, Ukraine

Zaporizhzhya Regional Clinical Hospital, Deartment of haematology and intensive therapy

🇺🇦

Zaporizhzhia, Ukraine

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