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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
143
375 mg/m2 IV on day 1 of each 21 days chemotherapy cycle. Number of Cycles: 8.
50 mg of doxorubicin per square meter administrated IV on day 1 of each chemotherapy cycle
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
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).
Time frame: 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).
Time frame: Week 13 to Week 26
Ctrough (Before 8th Infusion)
Trough serum concentration measured at the end of a dosing interval at steady state, taken directly before eighth infusion.
Time frame: Week 22
Cmax (Post 5th and 8th Infusion)
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)
Kel (Post 5th and 8th Infusions)
Elimination Rate Constant at steady stade after the 5th and 8th infusions.
Time frame: Week 13 (5th infusion) and Week 22 (8th infusion)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
750 mg of cyclophosphamide per square meter of body-surface area administrated IV on day 1 of each chemotherapy cycle
100 mg of prednisone administrated PO per day for five days, day 1-5 of each chemotherapy cycle
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, Bosnia and Herzegovina
GH "dr.Josip Bencevic"
Slavonski Brod, Croatia
CH Merkur
Zagreb, Croatia
CHC Zagreb
Zagreb, Croatia
HEMA
Tbilisi, Georgia
S. Khechinashvili state University clinic
Tbilisi, Georgia
Medulla - Chemotherapy and Immunotherapy Clinic
Tbilisi, Georgia
...and 25 more locations
T1/2 (Post 5th and 8th Infusions)
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
CLss (Post 5th and 8th Infusions)
Clearance at steady state after the 5th and 8th infusions.
Time frame: 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).
Time frame: 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))
Time frame: 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.
Time frame: 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).
Time frame: from baseline to Week 46