MabionCD20 Compared to MabThera in Lymphoma Patients

Phase 3

Completed

Conditions: Diffuse Large B-Cell Lymphoma

Interventions: Drug: Rituximab
Drug: Doxorubicin
Drug: Vincristine
Drug: Cyclophosphamide
Drug: prednisone

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

Patients with histological confirmed CD20 (cluster of differentiation 20) positive diffuse large B cell lymphoma (DLBCL)
Patients that had been diagnosed according to the WHO classification;
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

Life expectance less than 6 months;
Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment;
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

Group	Intervention	Description
MabionCD20	Cyclophosphamide	A 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
MabThera	Vincristine	A 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
MabionCD20	Vincristine	A 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
MabThera	prednisone	A 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
MabionCD20	Rituximab	A 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
MabionCD20	Doxorubicin	A 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
MabionCD20	prednisone	A 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
MabThera	Rituximab	A 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
MabThera	Doxorubicin	A 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
MabThera	Cyclophosphamide	A 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

Name	Time	Method
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

Name	Time	Method
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 26	Week 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 Events	from 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-cell	baseline 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): University Clinical Center Banja Luka
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Banja Luka, Bosnia and Herzegovina
University Clinical Center Sarajevo
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Sarajevo, Bosnia and Herzegovina
University Clinical Center Tuzla
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Tuzla, Bosnia and Herzegovina
General Hospital Zenica
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Zenica, Bosnia and Herzegovina
GH "dr.Josip Bencevic"
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Slavonski Brod, Croatia
CH Merkur
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Zagreb, Croatia
CHC Zagreb
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Zagreb, Croatia
HEMA
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Tbilisi, Georgia
S. Khechinashvili state University clinic
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Tbilisi, Georgia
Medulla - Chemotherapy and Immunotherapy Clinic
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Tbilisi, Georgia
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University Clinical Center Banja Luka
🇧🇦Banja Luka, Bosnia and Herzegovina