Diffuse Large B-Cell LymphomaPhase 3MADILYMNCT02617485
MabionCD20 Compared to MabThera in Lymphoma Patients
A Phase 3 study testing Rituximab, Doxorubicin and Vincristine in people with Diffuse Large B-Cell Lymphoma, run by Mabion SA at 35 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- Rituximab, Doxorubicin and Vincristine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 35 sitesin 7 countries
- Study dates
- Dec 2015to Jan 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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;
Trial locations and contacts
35 sites in 7 countries.
35 sites in 7 countries
Ukraine17 sites
Public utility "Chernivtsi regional clinical oncology dispensary", Day patient department
Chernivtsi, 58013
Municipal Institution "Dnipropetrovsk City multi-field Clinical Hospital #4", Oncology and medical radiology department
Dnipropetrovsk, 49102
Regional Clinical Hospital of Ivano-Frankivsk, Hematology Department.
Ivano-Frankivsk, 76008
Regional Clinical Oncology Dispensary, Chemotherapy Department
Ivano-Frankivsk, 76018
Kharkiv Regional Clinical Oncology Centre, Deartment of haematology
Kharkiv, 61070
National Institute of Cancer, Department of chemotherapy
Kiev, 03022
Kiev City Clinical Oncological Center, Department of chemotherapy #2
Kiev, 03115
Utility Enterprise "Kirovograd regional oncology dispensary"
Kirovohrad, 25011
Kryvyi Rih Oncology Dispensary, Dnipropetrovsk Highway
Kryvyi Rih, 50048
Volyn' Regional clinical hospital, Haematology Department
Lutsk, 45634
State institution "Institute for haemotopathology and haemotransfusion of National Academy of science of Ukraine
Lviv, 79044
Mykolayiv Region Clinical Hospital, Heamotology department
Mykolayiv, 54058
Poltava regional oncology hospital, heamotherapy department
Poltava, 36011
Regional clinical Hospital named after Novak, Hematology Department
Uzhhorod, 88000
Vinnitsya Regional Clinical Oncology Dispensary, Chemotherapy Department,
Vinnitsya, 21029
Regional Oncology dispensary
Zaporizhzhya, 69040
Zaporizhzhya Regional Clinical Hospital, Deartment of haematology and intensive therapy
Zaporizhzhya, 69600
Bosnia and Herzegovina4 sites
University Clinical Center Banja Luka
Banja Luka, 78 000
University Clinical Center Sarajevo
Sarajevo, 71 000
University Clinical Center Tuzla
Tuzla, 75 000
General Hospital Zenica
Zenica, 72 000
Poland4 sites
Wojewódzki Szpital Specjalistyczny w Legnicy, Oddział Hematologiczny
Legnica, 59-220
Samodzielny Publiczny Szpital Kliniczny nr1, Klinika Hematologii i Transplantacji Szpiku
Lublin, 20-081
Szpital Wojewódzki w Opolu, Oddział Hematologii i Onkologii Hematologicznej
Opole, 45-061
MTZ Clinical Research Sp. Z o.o.
Warsaw, 02-106
Croatia3 sites
GH "dr.Josip Bencevic"
Slavonski Brod, 35000
CH Merkur
Zagreb, 10000
CHC Zagreb
Zagreb, 10000
Georgia3 sites
HEMA
Tbilisi, 0112
S. Khechinashvili state University clinic
Tbilisi, 0179
Medulla - Chemotherapy and Immunotherapy Clinic
Tbilisi, 0186
Serbia3 sites
Clinical Hospital Center Zemun
Belgrade, 11000
Clinical Hospital Center Zvezdara
Belgrade, 11000
Military Hospital Academy
Belgrade, 11000
About this study
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
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.
Read the 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.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, prednisone
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called MabThera®, MabionCD20®
375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8.
DoxorubicinDrug
Also called Hydroxydaunorubicin
50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle
VincristineDrug
Also called Oncovine
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
CyclophosphamideDrug
750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle
prednisoneDrug
100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle
| Study group | Role | What they receive |
|---|---|---|
| MabionCD20 | Experimental | 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 Receives: Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: prednisone |
| MabThera | Active comparator | 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 Receives: Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Week 13 to Week 26
Secondary outcomes (9)
Ctrough (Before 8th Infusion)
Trough serum concentration measured at the end of a dosing interval at steady state, taken directly before eighth infusion.
Measured: Week 22
Cmax (Post 5th and 8th Infusion)
Maximum serum drug concentration (Cmax) at steady state after the 5th and 8th infusions.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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))
Measured: 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.
Measured: 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).
Measured: from baseline to Week 46
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionAug 2017
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mabion SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02617485
- Sponsor's protocol ID
- MabionCD20-002NHL
- Acronym
- MADILYM
- Status last verified
- Jan 2023
- First submitted
- 12 Nov 2015
- Last updated
- 25 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02617485
- Acronym / sponsor ID
- MADILYM / MabionCD20-002NHL
- Conditions
- Diffuse Large B-Cell Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Mabion SAIndustry (pharma, biotech, devices)
- Study start
- Dec 2015 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 1 Dec 2015 (estimated)
- Results
- Posted 25 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MabionCD20 | Experimental | Drug: Rituximab, Drug: Doxorubicin, Drug: Vincristine, Drug: Cyclophosphamide, Drug: prednisoneA 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 | Active comparator | Drug: Rituximab, Drug: Doxorubicin, Drug: Vincristine, Drug: Cyclophosphamide, Drug: prednisoneA 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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;
Key exclusion criteria (3 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: MabThera®, MabionCD20®375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8. | Drug | MabThera, MabionCD20 |
| DoxorubicinAlso: Hydroxydaunorubicin50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle | Drug | MabThera, MabionCD20 |
| VincristineAlso: Oncovine1.4 mg of vincristine per square meter, up to a maximal dose of 2 mg, administrated IV on day 1 of each chemotherapy cycle | Drug | MabThera, MabionCD20 |
| Cyclophosphamide750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle | Drug | MabThera, MabionCD20 |
| prednisone100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle | Drug | MabThera, MabionCD20 |
Primary outcome
Area Under the Serum Concentration-time Curve From Day 1 to Week 4 (AUC[1-4])
Time frame: 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])
Time frame: 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).
9 secondary outcomes
Ctrough (Before 8th Infusion)
Time frame: Week 22
Cmax (Post 5th and 8th Infusion)
Time frame: Week 13 (5th infusion) and Week 22 (8th infusion)
Kel (Post 5th and 8th Infusions)
Time frame: Week 13 (5th infusion) and Week 22 (8th infusion)
T1/2 (Post 5th and 8th Infusions)
Time frame: Week 13 to Week 16 and Week 22 to Week 26
CLss (Post 5th and 8th Infusions)
Time frame: Week 13 to Week 16 and Week 22 to Week 26
AUC (W1-W26) B-cell
Time frame: baseline to Week 26
AUC (W1-W26)
Time frame: Week 1 until Week 26
Efficacy Assessment at Week 26
Time frame: Week 26
Adverse Events
Time frame: from baseline to Week 46
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab, Doxorubicin and Vincristine in people with Diffuse Large B-Cell Lymphoma, run by Mabion SA at 35 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Ukraine, Bosnia and Herzegovina, Poland, Croatia, Georgia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Serum Concentration-time Curve From Day 1 to Week 4 (AUC[1-4]) (time frame: Baseline to Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2023.