A Trial to Evaluate the Efficacy and Safety of Tafasitamab With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT02763319
- Lead Sponsor
- Incyte Corporation
- Brief Summary
The purpose of the study is to compare the safety and efficacy of Tafasitamab with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.
- Detailed Description
This is a randomised, two-arm, multicentre, open-label phase II/III efficacy and safety study of Tafasitamab in combination with BEN versus RTX in combination with BEN given to adult patients who have relapsed after or are refractory to at least one but no more than three prior systemic therapies and have failed, or are not candidates for HDC and ASCT, and have thus exhausted their therapeutic options of demonstrated clinical benefit. At least one prior therapy line must have included a CD20-targeted therapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 453
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rituximab and bendamustine Rituximab (RTX) Rituximab and bendamustine Tafasitamab and bendamustine Bendamustine (BEN) Tafasitamab and bendamustine Rituximab and bendamustine Bendamustine (BEN) Rituximab and bendamustine Tafasitamab and bendamustine Tafasitamab Tafasitamab and bendamustine
- Primary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population up to 41.4 months Progression-free survival was defined as the time from randomization to tumor progression or death from any cause.
Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup up to 46.5 months Progression-free survival was defined as the time from randomization to tumor progression or death from any cause.
- Secondary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population up to 40.2 months Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup up to 44.7 months Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Kaplan-Meier Estimate of Overall Survival in the Overall Population up to 50.0 months Overall survival was defined as the time (in months) from randomization until death from any cause.
Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup up to 50.6 months Overall survival was defined as the time (in months) from randomization until death from any cause.
Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population up to 77 months DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD) based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or progressive disease (PD; any new lesion or an increase by ≥50% of previously involved sites from nadir).
DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup up to 77 months DCR was defined as the percentage of participants with a CR, PR, or SD based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or PD (any new lesion or an increase by ≥50% of previously involved sites from nadir).
Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Overall Population up to 25.8 months Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation.
Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup up to 40.6 months Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation.
Kaplan-Meier Estimate of Time to Next Treatment in the Overall Population up to 59.4 months Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first.
Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup up to 70.1 months Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) up to 77 months An adverse event was defined as any untoward medical occurrence in a participant administered a medicinal product, which did not necessarily have a causal relationship to this treatment. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it was considered related to that study drug. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
Number of Participants With Any Grade 3 or Higher TEAE up to 77 months AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (or higher). Grade 1: mild; asymptomatic or mild symptoms. Grade 2: moderate. Grade 3: severe or medically significant but not immediately life threatening. Grade 4: life-threatening consequences. Grade 5: death. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population up to 77 months Best ORR was defined as the percentage of patients with complete response (CR) or partial response (PR) based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup up to 77 months Best ORR was defined as the percentage of patients with CR or PR based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites.
Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population Baseline; End of Treatment (EOT) (up to 77 months) The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.
Change From Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup Baseline; End of Treatment (EOT) (up to 77 months) The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.
Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population Baseline; End of Treatment (EOT) (up to 77 months) The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population Baseline; End of Treatment (EOT) (up to 77 months) The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Change From Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup Baseline; End of Treatment (EOT) (up to 77 months) The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Change From Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup Baseline; End of Treatment (EOT) (up to 77 months) The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 \[worst overall health\] to 100 \[best overall health\]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
Tafasitamab Serum Concentrations pre-dose: Cycle 1 Days 1, 2, 3, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15, Cycles 4, 5, 6, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 Day 1. 1 hour post-dose: Cycle 1 Days 1, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15 Blood samples were collected for the assessment of serum concentrations of tafasitamab.
Trial Locations
- Locations (5)
MorphoSys Research Site
🇬🇧Southend on Sea, United Kingdom
Morphosys Research Site
🇬🇧Birmingham, United Kingdom
Morphosys Research site
🇨🇿Olomouc, Czechia
MorphoSys Research SIte
🇦🇺Garran, Australia
MorphoSys
🇪🇸Sabadell, Spain
MorphoSys Research Site🇬🇧Southend on Sea, United Kingdom