Diffuse Large B-cell Lymphoma
Conditions
Keywords
Non-Hodgkin Lymphoma, DLBCL, Diffuse large b-cell lymphoma
Brief summary
This is a multicenter, double-blind, randomized study comparing the efficacy, pharmacokinetics (PK)/pharmacodynamics (PD), safety and immunogenicity profile of RTXM83 (rituximab biosimilar) vs reference rituximab (MabThera®), both with CHOP, as first-line treatment of Diffuse-Large-B-Cell-Lymphoma (DLBCL). Rituximab biosimilar and MabThera® were both administered intravenously on Day 1 of each 3-week cycle with CHOP chemotherapy for six cycles. Two additional cycles of treatment were permitted at the Investigator's discretion. Patients were followed up for 9 months after last study dose.
Detailed description
The primary endpoint of the investigation is to determine if the response rate obtained with RTXM83 combined with CHOP is non inferior to the response rate obtained with reference rituximab combined with CHOP. The present study is a non inferiority trial and the study hypothesis is the following: H0: pc ≥ pe + δ vs. H1: pc \< pe + δ where, pe: proportion of successes in the experimental group (RTXM83+CHOP) pc: proportion of successes in the control group (Reference Rituximab+CHOP) Type I error: the difference pc-pe is less than δ when in fact the difference is greater than or equal to δ ie, the investigators choose the experimental treatment when the control treatment is actually substantially better. Type II error: the difference -pe is greater than or equal to δ when it is actually lest than δ ie, the investigators choose the control treatment when the experimental treatment is essentially just as good.
Interventions
BIOLOGICALRTXM83
Rituximab biosimilar (RTXM83) will be administered in combination with CHOP chemotherapy regimen (Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 up to a maximum of 2 mg on Day 1 plus Prednisone 40 mg/m2 or 100 mg per day from Day 1 to 5) at a dose of 375 mg/m2 on Day 1 of each 3 week cycle, for 6 cycles, although the administration of 2 additional cycles may be allowed.
BIOLOGICALMabthera
Mabthera will be administered in combination with CHOP chemotherapy regimen (Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 up to a maximum of 2 mg on Day 1 plus Prednisone 40 mg/m2 or 100 mg per day from Day 1 to 5) at a dose of 375 mg/m2 on Day 1 of each 3 week cycle, for 6 cycles, although the administration of 2 additional cycles may be allowed.
Sponsors
Pisa® Farmacéutica
Laboratorios de Productos Éticos C.E.I.S.A.
Laboratorio Elea Phoenix S.A.
Tecnoquimicas S.A
Innogene Kalbiotech Pte. Ltd
Libbs Farmacêutica LTDA
Key Oncologics (Pty) Ltd
Nanolek LLC
Actoverco
mAbxience Research S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with measurable disease defined as existence of a unidimensional or bidimensional lesion greater than 2 cm in its longest diameter or malignant lymphocytosis greater than 5x109/L. Any other procedure for measurable disease in particular cases, may be allowed upon Sponsor approval 2. Newly diagnosed patients with a confirmed pathologic diagnosis of Diffuse large B cell-non-Hodgkin's lymphoma (DLBCL) with untreated CD20+ receptor (CD20+). Defined by the local Haematopathologist at the local laboratory according to World Health Organization (WHO) criteria 3. Stage II-III or IV or stage I with bulk defined by the referring physician on the basis of the Cotswolds modification of the Ann Arbor classification 2 4. Age-adjusted International Prognostic Index (IPI) score 0 or 1 5. Age ≥18 to ≤65 years of age 6. Performance status according to Eastern Cooperative Oncology Group (ECOG) of ≤2 7. Written informed consent obtained before starting any study-specific procedure 8. Females of child-bearing potential must test negative on standard serum pregnancy test and must be willing to practice appropriate contraceptive methods for the duration of the study (e.g. oral contraceptive, double barrier method, intra-uterine device, intra-muscular contraceptive) 9. All male patients must take adequate contraceptive precautions during the course of the study
Exclusion criteria
1. Life expectancy of less than three months 2. Any other lymphoma other than CD20+ DLBCL 3. Indolent lymphoma, Primary central nervous system (CNS) Lymphoma or gastro-intestinal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma 4. Known hypersensitivity to active ingredients, excipients and murine and foreign proteins 5. Concurrent disease or general status that would exclude giving the treatment as outlined in the protocol 6. Active uncontrolled infection requiring systemic treatment with antibiotics or antiviral agents at Screening or history of documented recurrent clinically significant infection (e.g. 2 or more viral, bacterial or fungal infections requiring inpatient treatment) 7. Cardiac contra-indication to Doxorubicin therapy: non-compensated heart failure, dilated cardiomyopathy, coronary heart disease with ST segment depression on electrocardiogram (ECG), myocardial infarction in the last 6 months 8. Neurologic contra-indication to Vincristine as it is indicated in the Summary of Product Characteristics (SmPC): (e.g. peripheral neuropathy) 9. Chronic lung disease with hypoxemia measured by pulse oximetry (gasometry is not mandatory) 10. Severe uncontrolled hypertension, despite optimal medical treatment 11. Severe uncontrolled diabetes mellitus, despite optimal medical treatment 12. Renal insufficiency (Serum Creatinine \>2 x Upper Normal Limit \[UNL\]) 13. Hepatic insufficiency: aspartate aminotransferase (AST)/ alanine aminotransferase (ALT)\>3 x UNL or \>5 x UNL with involvement of the liver, total bilirubin \>34.2 µmol/L, or both) not related to lymphoma 14. Clinical signs of cerebral dysfunction 15. Severe psychiatric disease 16. Known human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C 17. Abnormal bone marrow function (platelets \<100x109/L, neutrophils \<1.5x109/L and Haemoglobin \<9g/dL) 18. Post-transplantation lymphoproliferative disease 19. Pregnant or lactating women or women that intend to get pregnant during study or within 12 months following the last infusion 20. Treatment with any investigational product in the 30 days period before inclusion in the study 21. Prior radiotherapy to treat the DLBCL Non-Hodgkin's Lymphoma (NHL) 22. Limitation of the patient's ability to comply with the treatment or follow-up protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL | Tumor response assessed after Cycle 6 or at the end of treatment | Per International Working Group (IWG) revised criteria for Malignant Lymphomas (Cheson et al. 2007) and assessed by positron-emission tomography scan, or by computed tomography scan and/or magnetic resonance imaging if Positron Emission Tomography (PET) scan was not feasible. Tumor response was classified according to the International Working Group criteria, as Complete Remission (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; Partial Response (PR): At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses; Stable disease (SD) or; Progressive disease. Response rate was the sum of CR and PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC 0-∞ (h μg/mL) at Cycle 6 of RTXM83 and Mabthera® | Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21 | Compare the PK parameter (AUC 0-∞) calculated from start of the first infusion until Day 21 of administration of Cycle 6 in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%. |
| Cmax (μg/mL) at Cycle 1 of RTXM83 and Mabthera® | Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15 | Compare the PK parameter (Cmax) calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1) in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (Cmax) falls completely within the range 80%-125%. |
| Cmax (μg/mL) at Cycle 6 of RTXM83 and Mabthera® | Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21 | Compare the PK parameter (Cmax) calculated from start of the first infusion until Day 21 of administration of Cycle 6 in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%. |
| AUC 0-∞ (h μg/mL) at Cycle 1 of RTXM83 and Mabthera® | Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15 | Compare the pharmacokinetic (PK) parameter (AUC 0-∞) calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1) in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%. |
| Comparable Safety Profile in Both Treatment Arms | Up to FU3; 9 months after last dose of treatment | Compare the frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) reported in each treatment arm. |
| Comparable Immunogenicity Profile Between RTXM83 and Mabthera® | Up to FU3; 9 months after last dose of treatment | Anti-Drug Antibody (ADA) developed de novo (seroconversion) after 6 cycles of treatment and 9 months of follow-up. |
| Event Free Survival (EFS) in RTXM83 Arm and Mabthera® Arm | Up to FU3; 9 months after last dose of treatment | Time from randomization to any of the following events: progressive disease, no achievement of CR, PR associated with treatment in excess of that per protocol, SD, relapse after achievement of CR, or death from any cause, whichever comes first. |
| Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | Up to follow-up 3 (FU3); 9 months after last dose of treatment | CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+. To compare the percent Change From Baseline ((Cycle 1 pre-dose) in pharmacodynamic markers (CD19+ and CD20+ Cells) in Peripheral Blood achieved in RTXM83 and Mabthera® arms at Cycle 1 end of infusion (EOI), 6 months and 9 months after last dose of treatment. |
Countries
Argentina, Brazil, Colombia, India, Indonesia, Iran, Malaysia, Mexico, Paraguay, Philippines, Russia, South Africa
Participant flow
Pre-assignment details
An additional cohort of 16 patients was added (as per Iran local regulatory requirements) to the planned sample of 256 patients. The extension cohort of Iran was only considered for safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| RTXM83-CHOP Patients treated with Rituximab biosimilar in combination with CHOP chemotherapy | 136 |
| MabThera-CHOP Patients treated with Rituximab in combination with CHOP chemotherapy | 136 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 7 |
| Overall Study | Death | 4 | 4 |
| Overall Study | Disease Progression | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Total | RTXM83-CHOP | MabThera-CHOP |
|---|---|---|---|
| Age-adjusted International Prognostic Index (IPI) 0 | 98 Participants | 48 Participants | 50 Participants |
| Age-adjusted International Prognostic Index (IPI) 1 | 164 Participants | 85 Participants | 79 Participants |
| Age-adjusted International Prognostic Index (IPI) 2 | 10 Participants | 3 Participants | 7 Participants |
| Age, Continuous | 51.0 years | 49.0 years | 51.0 years |
| Initial disease stage (Ann Arbor Staging) Stage II | 117 Participants | 64 Participants | 53 Participants |
| Initial disease stage (Ann Arbor Staging) Stage III | 62 Participants | 30 Participants | 32 Participants |
| Initial disease stage (Ann Arbor Staging) Stage IV | 55 Participants | 23 Participants | 32 Participants |
| Initial disease stage (Ann Arbor Staging) Stage I (with bulky) | 38 Participants | 19 Participants | 19 Participants |
| Performance Status according to Eastern Cooperative Oncology Group (ECOG) 0 | 168 Participants | 84 Participants | 84 Participants |
| Performance Status according to Eastern Cooperative Oncology Group (ECOG) 1 | 102 Participants | 52 Participants | 50 Participants |
| Performance Status according to Eastern Cooperative Oncology Group (ECOG) Missing data | 2 Participants | 0 Participants | 2 Participants |
| Presence of extra nodal lesions No | 169 Participants | 88 Participants | 81 Participants |
| Presence of extra nodal lesions Yes | 103 Participants | 48 Participants | 55 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 103 Participants | 50 Participants | 53 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 153 Participants | 75 Participants | 78 Participants |
| Sex: Female, Male Female | 117 Participants | 58 Participants | 59 Participants |
| Sex: Female, Male Male | 155 Participants | 78 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 136 | 12 / 136 |
| other Total, other adverse events | 131 / 136 | 131 / 136 |
| serious Total, serious adverse events | 47 / 136 | 45 / 136 |
Outcome results
Primary
Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL
Per International Working Group (IWG) revised criteria for Malignant Lymphomas (Cheson et al. 2007) and assessed by positron-emission tomography scan, or by computed tomography scan and/or magnetic resonance imaging if Positron Emission Tomography (PET) scan was not feasible. Tumor response was classified according to the International Working Group criteria, as Complete Remission (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; Partial Response (PR): At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses; Stable disease (SD) or; Progressive disease. Response rate was the sum of CR and PR.
Time frame: Tumor response assessed after Cycle 6 or at the end of treatment
Population: The Intent-to-treat (ITT) population and the Per Protocol (PP) population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RTXM83-CHOP | Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL | ITT : Response rate (CR+PR) | 83.6 percentage of participants |
| RTXM83-CHOP | Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL | PP : Response rate (CR+PR) | 84.7 percentage of participants |
| MabThera-CHOP | Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL | ITT : Response rate (CR+PR) | 82.9 percentage of participants |
| MabThera-CHOP | Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL | PP : Response rate (CR+PR) | 81.7 percentage of participants |
Secondary
AUC 0-∞ (h μg/mL) at Cycle 1 of RTXM83 and Mabthera®
Compare the pharmacokinetic (PK) parameter (AUC 0-∞) calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1) in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%.
Time frame: Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTXM83-CHOP | AUC 0-∞ (h μg/mL) at Cycle 1 of RTXM83 and Mabthera® | 44519 ng.h/mL | Geometric Coefficient of Variation 32 |
| MabThera-CHOP | AUC 0-∞ (h μg/mL) at Cycle 1 of RTXM83 and Mabthera® | 44874 ng.h/mL | Geometric Coefficient of Variation 47 |
90% CI: [93.6, 105]
Secondary
AUC 0-∞ (h μg/mL) at Cycle 6 of RTXM83 and Mabthera®
Compare the PK parameter (AUC 0-∞) calculated from start of the first infusion until Day 21 of administration of Cycle 6 in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%.
Time frame: Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTXM83-CHOP | AUC 0-∞ (h μg/mL) at Cycle 6 of RTXM83 and Mabthera® | 60875 ng.h/mL | Geometric Coefficient of Variation 22 |
| MabThera-CHOP | AUC 0-∞ (h μg/mL) at Cycle 6 of RTXM83 and Mabthera® | 59079 ng.h/mL | Geometric Coefficient of Variation 40 |
90% CI: [98.5, 107]
Secondary
Cmax (μg/mL) at Cycle 1 of RTXM83 and Mabthera®
Compare the PK parameter (Cmax) calculated from start of the first infusion until start of the second infusion (i.e. at Cycle 1) in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (Cmax) falls completely within the range 80%-125%.
Time frame: Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTXM83-CHOP | Cmax (μg/mL) at Cycle 1 of RTXM83 and Mabthera® | 196.8 μg/mL | Geometric Coefficient of Variation 24 |
| MabThera-CHOP | Cmax (μg/mL) at Cycle 1 of RTXM83 and Mabthera® | 197.5 μg/mL | Geometric Coefficient of Variation 31 |
90% CI: [93.9, 105]
Secondary
Cmax (μg/mL) at Cycle 6 of RTXM83 and Mabthera®
Compare the PK parameter (Cmax) calculated from start of the first infusion until Day 21 of administration of Cycle 6 in a population PK model. For the PK similarity assessments, regulatory guidelines on bioequivalence were followed whereby two treatments are judged not to be different from one another if the 90% confidence interval (CI) of the ratio between the geometric means of the measure (AUC 0-∞ ) falls completely within the range 80%-125%.
Time frame: Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTXM83-CHOP | Cmax (μg/mL) at Cycle 6 of RTXM83 and Mabthera® | 291 μg/mL | Geometric Coefficient of Variation 21 |
| MabThera-CHOP | Cmax (μg/mL) at Cycle 6 of RTXM83 and Mabthera® | 279 μg/mL | Geometric Coefficient of Variation 36 |
90% CI: [99.5, 109]
Secondary
Comparable Immunogenicity Profile Between RTXM83 and Mabthera®
Anti-Drug Antibody (ADA) developed de novo (seroconversion) after 6 cycles of treatment and 9 months of follow-up.
Time frame: Up to FU3; 9 months after last dose of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RTXM83-CHOP | Comparable Immunogenicity Profile Between RTXM83 and Mabthera® | No seroconversion | 124 Participants |
| RTXM83-CHOP | Comparable Immunogenicity Profile Between RTXM83 and Mabthera® | Seroconversion | 3 Participants |
| MabThera-CHOP | Comparable Immunogenicity Profile Between RTXM83 and Mabthera® | No seroconversion | 121 Participants |
| MabThera-CHOP | Comparable Immunogenicity Profile Between RTXM83 and Mabthera® | Seroconversion | 4 Participants |
Secondary
Comparable Safety Profile in Both Treatment Arms
Compare the frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) reported in each treatment arm.
Time frame: Up to FU3; 9 months after last dose of treatment
Population: All patients receiving at least one dose of the study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RTXM83-CHOP | Comparable Safety Profile in Both Treatment Arms | At least one TEAE (any causality) | 131 Participants |
| RTXM83-CHOP | Comparable Safety Profile in Both Treatment Arms | TEAEs related to treatment | 125 Participants |
| RTXM83-CHOP | Comparable Safety Profile in Both Treatment Arms | Serious TEAEs (any causality) | 47 Participants |
| RTXM83-CHOP | Comparable Safety Profile in Both Treatment Arms | TEAE led to drug discontinuation (any causality) | 6 Participants |
| RTXM83-CHOP | Comparable Safety Profile in Both Treatment Arms | At least one grade 3/4 TEAE (any causality) | 75 Participants |
| MabThera-CHOP | Comparable Safety Profile in Both Treatment Arms | TEAE led to drug discontinuation (any causality) | 7 Participants |
| MabThera-CHOP | Comparable Safety Profile in Both Treatment Arms | At least one TEAE (any causality) | 131 Participants |
| MabThera-CHOP | Comparable Safety Profile in Both Treatment Arms | At least one grade 3/4 TEAE (any causality) | 80 Participants |
| MabThera-CHOP | Comparable Safety Profile in Both Treatment Arms | Serious TEAEs (any causality) | 45 Participants |
| MabThera-CHOP | Comparable Safety Profile in Both Treatment Arms | TEAEs related to treatment | 119 Participants |
Secondary
Event Free Survival (EFS) in RTXM83 Arm and Mabthera® Arm
Time from randomization to any of the following events: progressive disease, no achievement of CR, PR associated with treatment in excess of that per protocol, SD, relapse after achievement of CR, or death from any cause, whichever comes first.
Time frame: Up to FU3; 9 months after last dose of treatment
Population: Number of patients with an EFS event (progressive disease, no achievement of CR, PR associated with treatment more than that per protocol, stable disease, relapse after achievement of CR, or death from any cause, whichever comes first).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RTXM83-CHOP | Event Free Survival (EFS) in RTXM83 Arm and Mabthera® Arm | 12.5 time (months) |
| MabThera-CHOP | Event Free Survival (EFS) in RTXM83 Arm and Mabthera® Arm | 8.6 time (months) |
p-value: 0.457Log Rank
Secondary
Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera®
CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+. To compare the percent Change From Baseline ((Cycle 1 pre-dose) in pharmacodynamic markers (CD19+ and CD20+ Cells) in Peripheral Blood achieved in RTXM83 and Mabthera® arms at Cycle 1 end of infusion (EOI), 6 months and 9 months after last dose of treatment.
Time frame: Up to follow-up 3 (FU3); 9 months after last dose of treatment
Population: Data were provided for the number of samples available at each visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RTXM83-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | Cycle 1 EOI, CD19+ | -96.8 percentage change in cells |
| RTXM83-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 6 months after last dose, CD19+ | -95.7 percentage change in cells |
| RTXM83-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 9 months after last dose, CD19+ | -33 percentage change in cells |
| RTXM83-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | Cycle 1 EOI, CD20+ | -100 percentage change in cells |
| RTXM83-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 6 months after last dose, CD20+ | -98.9 percentage change in cells |
| RTXM83-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 9 months after last dose, CD20+ | -22.2 percentage change in cells |
| MabThera-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 6 months after last dose, CD20+ | -100 percentage change in cells |
| MabThera-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | Cycle 1 EOI, CD19+ | -94.6 percentage change in cells |
| MabThera-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | Cycle 1 EOI, CD20+ | -100 percentage change in cells |
| MabThera-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 6 months after last dose, CD19+ | -98.3 percentage change in cells |
| MabThera-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 9 months after last dose, CD20+ | -30.6 percentage change in cells |
| MabThera-CHOP | Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® | At 9 months after last dose, CD19+ | -42.3 percentage change in cells |