MabionCD20 Compared to MabThera in Lymphoma Patients (MADILYM)

Randomized, Parallel-group, Double-blind, Comparative Bioequivalence Trial of MabionCD20 Compared to MabThera (Rituximab by Hoffman-La Roche) in Patients With Diffuse Large B-cell Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: prednisone

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.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78 000
    • University Clinical Center Banja Luka
  • Sarajevo, Bosnia and Herzegovina, 71 000
    • University Clinical Center Sarajevo
  • Tuzla, Bosnia and Herzegovina, 75 000
    • University Clinical Center Tuzla
  • Zenica, Bosnia and Herzegovina, 72 000
    • General Hospital Zenica
• Croatia
  • Slavonski Brod, Croatia, 35000
    • GH "dr.Josip Bencevic"
  • Zagreb, Croatia, 10000
    • CHC Zagreb
  • Zagreb, Croatia, 10000
    • CH Merkur
• Georgia
  • Tbilisi, Georgia, 0112
    • HEMA
  • Tbilisi, Georgia, 0179
    • S. Khechinashvili state University clinic
  • Tbilisi, Georgia, 0186
    • Medulla - Chemotherapy and Immunotherapy Clinic
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • Institut of Oncology, Hematology Department
• Poland
  • Legnica, Poland, 59-220
    • Wojewódzki Szpital Specjalistyczny w Legnicy, Oddział Hematologiczny
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr1, Klinika Hematologii i Transplantacji Szpiku
  • Opole, Poland, 45-061
    • Szpital Wojewódzki w Opolu, Oddział Hematologii i Onkologii Hematologicznej
  • Warsaw, Poland, 02-106
    • MTZ Clinical Research Sp. z o.o.
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zvezdara
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zemun
  • Belgrade, Serbia, 11000
    • Military Hospital Academy
• Ukraine
  • Chernivtsi, Ukraine, 58013
    • Public utility "Chernivtsi regional clinical oncology dispensary", Day patient department
  • Dnipropetrovsk, Ukraine, 49102
    • Municipal Institution "Dnipropetrovsk City multi-field Clinical Hospital #4", Oncology and medical radiology department
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital of Ivano-Frankivsk, Hematology Department.
  • Ivano-Frankivsk, Ukraine, 76018
    • Regional Clinical Oncology Dispensary, Chemotherapy Department
  • Kharkiv, Ukraine, 61070
    • Kharkiv Regional Clinical Oncology Centre, Deartment of haematology
  • Kiev, Ukraine, 03022
    • National Institute of Cancer, Department of chemotherapy
  • Kiev, Ukraine, 03115
    • Kiev City Clinical Oncological Center, Department of chemotherapy #2
  • Kirovohrad, Ukraine, 25011
    • Utility Enterprise "Kirovograd regional oncology dispensary"
  • Kryvyi Rih, Ukraine, 50048
    • Kryvyi Rih Oncology Dispensary, Dnipropetrovsk Highway
  • Lutsk, Ukraine, 45634
    • Volyn' Regional clinical hospital, Haematology Department
  • Lviv, Ukraine, 79044
    • State institution "Institute for haemotopathology and haemotransfusion of National Academy of science of Ukraine
  • Mykolayiv, Ukraine, 54058
    • Mykolayiv Region Clinical Hospital, Heamotology department
  • Poltava, Ukraine, 36011
    • Poltava regional oncology hospital, heamotherapy department
  • Uzhgorod, Ukraine, 88000
    • Regional clinical Hospital named after Novak, Hematology Department
  • Vinnitsya, Ukraine, 21029
    • Vinnitsya Regional Clinical Oncology Dispensary, Chemotherapy Department,
  • Zaporizhzhia, Ukraine, 69040
    • Regional Oncology Dispensary
  • Zaporizhzhia, Ukraine, 69600
    • Zaporizhzhya Regional Clinical Hospital, Deartment of haematology and intensive therapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MabionCD20; 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	Drug: Rituximab; 375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8.; Other Names: MabThera®, MabionCD20®; Drug: Doxorubicin; 50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle; Other Names: Hydroxydaunorubicin; Drug: Vincristine; 1.4 mg of vincristine per square meter, up to a maximal dose of 2 mg, administrated IV on day 1 of each chemotherapy cycle; Other Names: Oncovine; Drug: Cyclophosphamide; 750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle; Drug: prednisone; 100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle
Active Comparator: MabThera; 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	Drug: Rituximab; 375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8.; Other Names: MabThera®, MabionCD20®; Drug: Doxorubicin; 50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle; Other Names: Hydroxydaunorubicin; Drug: Vincristine; 1.4 mg of vincristine per square meter, up to a maximal dose of 2 mg, administrated IV on day 1 of each chemotherapy cycle; Other Names: Oncovine; Drug: Cyclophosphamide; 750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle; Drug: prednisone; 100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Serum Concentration-time Curve From Day 1 to Week 4 (AUC[1-4])	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).	Baseline to Week 4
Area Under the Serum Concentration-time Curve From Week 13 to Week 26 (AUC[W13-W26])	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).	Week 13 to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ctrough (Before 8th Infusion)	Trough serum concentration measured at the end of a dosing interval at steady state, taken directly before eighth infusion.	Week 22
Cmax (Post 5th and 8th Infusion)	Maximum serum drug concentration (Cmax) at steady state after the 5th and 8th infusions.	Week 13 (5th infusion) and Week 22 (8th infusion)
Kel (Post 5th and 8th Infusions)	Elimination Rate Constant at steady stade after the 5th and 8th infusions.	Week 13 (5th infusion) and Week 22 (8th infusion)
T1/2 (Post 5th and 8th Infusions)	Elimination half-life at steady state after the 5th and 8th infusions.	Week 13 to Week 16 and Week 22 to Week 26
CLss (Post 5th and 8th Infusions)	Clearance at steady state after the 5th and 8th infusions.	Week 13 to Week 16 and Week 22 to Week 26
AUC (W1-W26) B-cell	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).	baseline to Week 26
AUC (W1-W26)	Area under the serum concentration-time curve measured after the first administration (Week 1) until Week 26 (AUC(1-26))	Week 1 until Week 26
Efficacy Assessment at 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.	Week 26
Adverse Events	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).	from baseline to Week 46

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Percentage of patients with positive ADA or NAb results in a given category. Data pertain to the entire follow-up period (from Baseline to Week 46).	from baseline to Week 46

Collaborators and Investigators

• Sponsor: Mabion SA

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: November 12, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimated): December 1, 2015

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: MabionCD20-002NHL