MabionCD20 Compared to MabThera in Lymphoma Patients

Diffuse Large B-Cell Lymphoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02617485
• Other study ID #: MabionCD20-002NHL
• Status: Completed
• Phase: Phase 3
• Start date: December 2015
• Est. completion date: January 2018

Study information

• Verified date: January 2023
• Source: Mabion SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: January 2018
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8.
• Doxorubicin
50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle
• 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
• Cyclophosphamide
750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle
• prednisone
100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle

Locations

Country	Name	City	State
Bosnia and Herzegovina	University Clinical Center Banja Luka	Banja Luka
Bosnia and Herzegovina	University Clinical Center Sarajevo	Sarajevo
Bosnia and Herzegovina	University Clinical Center Tuzla	Tuzla
Bosnia and Herzegovina	General Hospital Zenica	Zenica
Croatia	GH "dr.Josip Bencevic"	Slavonski Brod
Croatia	CH Merkur	Zagreb
Croatia	CHC Zagreb	Zagreb
Georgia	HEMA	Tbilisi
Georgia	Medulla - Chemotherapy and Immunotherapy Clinic	Tbilisi
Georgia	S. Khechinashvili state University clinic	Tbilisi
Moldova, Republic of	Institut of Oncology, Hematology Department	Chisinau
Poland	Wojewódzki Szpital Specjalistyczny w Legnicy, Oddzial Hematologiczny	Legnica
Poland	Samodzielny Publiczny Szpital Kliniczny nr1, Klinika Hematologii i Transplantacji Szpiku	Lublin
Poland	Szpital Wojewódzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej	Opole
Poland	MTZ Clinical Research Sp. Z o.o.	Warsaw
Serbia	Clinical Hospital Center Zemun	Belgrade
Serbia	Clinical Hospital Center Zvezdara	Belgrade
Serbia	Military Hospital Academy	Belgrade
Ukraine	Public utility "Chernivtsi regional clinical oncology dispensary", Day patient department	Chernivtsi
Ukraine	Municipal Institution "Dnipropetrovsk City multi-field Clinical Hospital #4", Oncology and medical radiology department	Dnipropetrovsk
Ukraine	Regional Clinical Hospital of Ivano-Frankivsk, Hematology Department.	Ivano-Frankivsk
Ukraine	Regional Clinical Oncology Dispensary, Chemotherapy Department	Ivano-Frankivsk
Ukraine	Kharkiv Regional Clinical Oncology Centre, Deartment of haematology	Kharkiv
Ukraine	Kiev City Clinical Oncological Center, Department of chemotherapy #2	Kiev
Ukraine	National Institute of Cancer, Department of chemotherapy	Kiev
Ukraine	Utility Enterprise "Kirovograd regional oncology dispensary"	Kirovohrad
Ukraine	Kryvyi Rih Oncology Dispensary, Dnipropetrovsk Highway	Kryvyi Rih
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	Mykolayiv Region Clinical Hospital, Heamotology department	Mykolayiv
Ukraine	Poltava regional oncology hospital, heamotherapy department	Poltava
Ukraine	Regional clinical Hospital named after Novak, Hematology Department	Uzhgorod
Ukraine	Vinnitsya Regional Clinical Oncology Dispensary, Chemotherapy Department,	Vinnitsya
Ukraine	Regional Oncology dispensary	Zaporizhzhia
Ukraine	Zaporizhzhya Regional Clinical Hospital, Deartment of haematology and intensive therapy	Zaporizhzhia

Sponsors (1)

Lead Sponsor	Collaborator
Mabion SA

Countries where clinical trial is conducted

Bosnia and Herzegovina,  Croatia,  Georgia,  Moldova, Republic of,  Poland,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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