Back to resultsMabionCD20 Compared to MabThera in Lymphoma Patients (MADILYM)
Primary Purpose
Diffuse Large B-Cell Lymphoma
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rituximab
Doxorubicin
Vincristine
Cyclophosphamide
prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma
Eligibility Criteria
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;
Sites / Locations
- University Clinical Center Banja Luka
- University Clinical Center Sarajevo
- University Clinical Center Tuzla
- General Hospital Zenica
- GH "dr.Josip Bencevic"
- CH Merkur
- CHC Zagreb
- HEMA
- S. Khechinashvili state University clinic
- Medulla - Chemotherapy and Immunotherapy Clinic
- Institut of Oncology, Hematology Department
- Wojewódzki Szpital Specjalistyczny w Legnicy, Oddział Hematologiczny
- Samodzielny Publiczny Szpital Kliniczny nr1, Klinika Hematologii i Transplantacji Szpiku
- Szpital Wojewódzki w Opolu, Oddział Hematologii i Onkologii Hematologicznej
- MTZ Clinical Research Sp. Z o.o.
- Clinical Hospital Center Zemun
- Clinical Hospital Center Zvezdara
- Military Hospital Academy
- Public utility "Chernivtsi regional clinical oncology dispensary", Day patient department
- Municipal Institution "Dnipropetrovsk City multi-field Clinical Hospital #4", Oncology and medical radiology department
- Regional Clinical Hospital of Ivano-Frankivsk, Hematology Department.
- Regional Clinical Oncology Dispensary, Chemotherapy Department
- Kharkiv Regional Clinical Oncology Centre, Deartment of haematology
- National Institute of Cancer, Department of chemotherapy
- Kiev City Clinical Oncological Center, Department of chemotherapy #2
- Utility Enterprise "Kirovograd regional oncology dispensary"
- Kryvyi Rih Oncology Dispensary, Dnipropetrovsk Highway
- Volyn' Regional clinical hospital, Haematology Department
- State institution "Institute for haemotopathology and haemotransfusion of National Academy of science of Ukraine
- Mykolayiv Region Clinical Hospital, Heamotology department
- Poltava regional oncology hospital, heamotherapy department
- Regional clinical Hospital named after Novak, Hematology Department
- Vinnitsya Regional Clinical Oncology Dispensary, Chemotherapy Department,
- Regional Oncology dispensary
- Zaporizhzhya Regional Clinical Hospital, Deartment of haematology and intensive therapy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
MabionCD20
MabThera
Arm Description
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
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
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
Ctrough (Before 8th Infusion)
Trough serum concentration measured at the end of a dosing interval at steady state, taken directly before eighth infusion.
Cmax (Post 5th and 8th Infusion)
Maximum serum drug concentration (Cmax) at steady state after the 5th and 8th infusions.
Kel (Post 5th and 8th Infusions)
Elimination Rate Constant at steady stade after the 5th and 8th infusions.
T1/2 (Post 5th and 8th Infusions)
Elimination half-life at steady state after the 5th and 8th infusions.
CLss (Post 5th and 8th Infusions)
Clearance at steady state after the 5th and 8th infusions.
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).
AUC (W1-W26)
Area under the serum concentration-time curve measured after the first administration (Week 1) until Week 26 (AUC(1-26))
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02617485
Brief Title
MabionCD20 Compared to MabThera in Lymphoma Patients
Acronym
MADILYM
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
December 2015 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
January 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mabion SA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
143 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MabionCD20
Arm Type
Experimental
Arm Description
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
Arm Title
MabThera
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera®, MabionCD20®
Intervention Description
375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Hydroxydaunorubicin
Intervention Description
50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle
Primary Outcome Measure Information:
Title
Area Under the Serum Concentration-time Curve From Day 1 to Week 4 (AUC[1-4])
Description
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).
Time Frame
Baseline to Week 4
Title
Area Under the Serum Concentration-time Curve From Week 13 to Week 26 (AUC[W13-W26])
Description
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).
Time Frame
Week 13 to Week 26
Secondary Outcome Measure Information:
Title
Ctrough (Before 8th Infusion)
Description
Trough serum concentration measured at the end of a dosing interval at steady state, taken directly before eighth infusion.
Time Frame
Week 22
Title
Cmax (Post 5th and 8th Infusion)
Description
Maximum serum drug concentration (Cmax) at steady state after the 5th and 8th infusions.
Time Frame
Week 13 (5th infusion) and Week 22 (8th infusion)
Title
Kel (Post 5th and 8th Infusions)
Description
Elimination Rate Constant at steady stade after the 5th and 8th infusions.
Time Frame
Week 13 (5th infusion) and Week 22 (8th infusion)
Title
T1/2 (Post 5th and 8th Infusions)
Description
Elimination half-life at steady state after the 5th and 8th infusions.
Time Frame
Week 13 to Week 16 and Week 22 to Week 26
Title
CLss (Post 5th and 8th Infusions)
Description
Clearance at steady state after the 5th and 8th infusions.
Time Frame
Week 13 to Week 16 and Week 22 to Week 26
Title
AUC (W1-W26) B-cell
Description
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).
Time Frame
baseline to Week 26
Title
AUC (W1-W26)
Description
Area under the serum concentration-time curve measured after the first administration (Week 1) until Week 26 (AUC(1-26))
Time Frame
Week 1 until Week 26
Title
Efficacy Assessment at Week 26
Description
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.
Time Frame
Week 26
Title
Adverse Events
Description
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).
Time Frame
from baseline to Week 46
Other Pre-specified Outcome Measures:
Title
Immunogenicity
Description
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).
Time Frame
from baseline to Week 46
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Facility Information:
Facility Name
University Clinical Center Banja Luka
City
Banja Luka
ZIP/Postal Code
78 000
Country
Bosnia and Herzegovina
Facility Name
University Clinical Center Sarajevo
City
Sarajevo
ZIP/Postal Code
71 000
Country
Bosnia and Herzegovina
Facility Name
University Clinical Center Tuzla
City
Tuzla
ZIP/Postal Code
75 000
Country
Bosnia and Herzegovina
Facility Name
General Hospital Zenica
City
Zenica
ZIP/Postal Code
72 000
Country
Bosnia and Herzegovina
Facility Name
GH "dr.Josip Bencevic"
City
Slavonski Brod
ZIP/Postal Code
35000
Country
Croatia
Facility Name
CH Merkur
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
CHC Zagreb
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
HEMA
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
S. Khechinashvili state University clinic
City
Tbilisi
ZIP/Postal Code
0179
Country
Georgia
Facility Name
Medulla - Chemotherapy and Immunotherapy Clinic
City
Tbilisi
ZIP/Postal Code
0186
Country
Georgia
Facility Name
Institut of Oncology, Hematology Department
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Wojewódzki Szpital Specjalistyczny w Legnicy, Oddział Hematologiczny
City
Legnica
ZIP/Postal Code
59-220
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny nr1, Klinika Hematologii i Transplantacji Szpiku
City
Lublin
ZIP/Postal Code
20-081
Country
Poland
Facility Name
Szpital Wojewódzki w Opolu, Oddział Hematologii i Onkologii Hematologicznej
City
Opole
ZIP/Postal Code
45-061
Country
Poland
Facility Name
MTZ Clinical Research Sp. Z o.o.
City
Warsaw
ZIP/Postal Code
02-106
Country
Poland
Facility Name
Clinical Hospital Center Zemun
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Clinical Hospital Center Zvezdara
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Military Hospital Academy
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Public utility "Chernivtsi regional clinical oncology dispensary", Day patient department
City
Chernivtsi
ZIP/Postal Code
58013
Country
Ukraine
Facility Name
Municipal Institution "Dnipropetrovsk City multi-field Clinical Hospital #4", Oncology and medical radiology department
City
Dnipropetrovsk
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Regional Clinical Hospital of Ivano-Frankivsk, Hematology Department.
City
Ivano-Frankivsk
ZIP/Postal Code
76008
Country
Ukraine
Facility Name
Regional Clinical Oncology Dispensary, Chemotherapy Department
City
Ivano-Frankivsk
ZIP/Postal Code
76018
Country
Ukraine
Facility Name
Kharkiv Regional Clinical Oncology Centre, Deartment of haematology
City
Kharkiv
ZIP/Postal Code
61070
Country
Ukraine
Facility Name
National Institute of Cancer, Department of chemotherapy
City
Kiev
ZIP/Postal Code
03022
Country
Ukraine
Facility Name
Kiev City Clinical Oncological Center, Department of chemotherapy #2
City
Kiev
ZIP/Postal Code
03115
Country
Ukraine
Facility Name
Utility Enterprise "Kirovograd regional oncology dispensary"
City
Kirovohrad
ZIP/Postal Code
25011
Country
Ukraine
Facility Name
Kryvyi Rih Oncology Dispensary, Dnipropetrovsk Highway
City
Kryvyi Rih
ZIP/Postal Code
50048
Country
Ukraine
Facility Name
Volyn' Regional clinical hospital, Haematology Department
City
Lutsk
ZIP/Postal Code
45634
Country
Ukraine
Facility Name
State institution "Institute for haemotopathology and haemotransfusion of National Academy of science of Ukraine
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
Facility Name
Mykolayiv Region Clinical Hospital, Heamotology department
City
Mykolayiv
ZIP/Postal Code
54058
Country
Ukraine
Facility Name
Poltava regional oncology hospital, heamotherapy department
City
Poltava
ZIP/Postal Code
36011
Country
Ukraine
Facility Name
Regional clinical Hospital named after Novak, Hematology Department
City
Uzhgorod
ZIP/Postal Code
88000
Country
Ukraine
Facility Name
Vinnitsya Regional Clinical Oncology Dispensary, Chemotherapy Department,
City
Vinnitsya
ZIP/Postal Code
21029
Country
Ukraine
Facility Name
Regional Oncology dispensary
City
Zaporizhzhia
ZIP/Postal Code
69040
Country
Ukraine
Facility Name
Zaporizhzhya Regional Clinical Hospital, Deartment of haematology and intensive therapy
City
Zaporizhzhia
ZIP/Postal Code
69600
Country
Ukraine
12. IPD Sharing Statement
Learn more about this trial
MabionCD20 Compared to MabThera in Lymphoma Patients
We'll reach out to this number within 24 hrs