Diffuse Large B-cell Lymphoma
Conditions
Keywords
DLBCL, CD19, monoclonal antibody, tafasitamab, lenalidomide, MOR208, MOR00208
Brief summary
This is an open-label, randomized, multicentre study to evaluate safety and preliminary efficacy of the human anti-CD19 antibody Tafasitamab in addition to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) or Tafasitamab and Lenalidomide in addition to R-CHOP in adult patients with newly diagnosed, previously untreated Diffuse Large B-cell Lymphoma (DLBCL).
Interventions
DRUGTafasitamab
Six 21-day cycles of tafasitamab (12 mg/kg intravenously, on Day 1, 8 and 15) in addition to R-CHOP
DRUGTafasitamab plus lenalidomide
Six 21-day cycles of tafasitamab (12 mg/kg intravenously, on Day 1, 8 and 15) plus lenalidomide (starting dose 25 mg orally, on Day 1-10) in addition to R-CHOP
Sponsors
MorphoSys AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: 1. Age \>18 years 2. Histologically confirmed diagnosis of DLBCL, not otherwise specified (NOS) 3. Tumor tissue for retrospective central pathology review and correlative studies must be provided. 4. At least one bidimensionally measurable, PET positive disease site (greatest transverse diameter of ≥1.5 cm, greatest perpendicular diameter of ≥1.0 cm) 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 6. International Prognostic Index (IPI) status of 2 to 5 7. Appropriate candidate for R-CHOP 8. Left ventricular ejection fraction (LVEF) of ≥50% assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan 9. Adequate hematologic, liver and renal function 10. Females of childbearing potential (FCBP) must: * not be pregnant * refrain from breast feeding and donating oocyte * agree to ongoing pregnancy testing * commit to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception 11. Males must: * use an effective barrier method of contraception if sexually active with FCBP * refrain from donating sperm 12. In the opinion of investigator, the patient must be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events Major
Exclusion criteria
1. Any other histological type of lymphoma according to World Health Organization (WHO) 2016 classification of lymphoid neoplasms, known double- or triple-hit lymphoma 2. Transformed non-Hodgkin lymphoma (NHL) and/or evidence of composite lymphoma 3. History of radiation therapy to ≥25% of the bone marrow or history of anthracycline therapy 4. History of prior non-hematologic malignancy except for the following: * Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening * Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer * Adequately treated carcinoma in situ without current evidence of disease 5. History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening arrhythmias 6. Patients with: * positive test results for active hepatitis B and C * known seropositive for or history of active viral infection with human immunodeficiency virus (HIV) * known active bacterial, viral, fungal, mycobacterial, or other infection at screening * known central nervous system (CNS) lymphoma involvement * history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator opinion preclude participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | 6 months approximately |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic, PET-negative Complete Response (CR) Rate at the End of Treatment | 6 months approximately | — |
| Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | 18 months for non-treatment emergent adverse events, 6 months for treatment emergent adverse events | — |
| Best Objective Response Rate (ORR) Until the End of Study (EOS) | 24 months approximately | The best ORR was defined as the proportion of patients with Complete Response (CR) or Partial Response (PR) as the best response until the EOS. |
| Metabolic, PET-negative Complete Response (CR) Rate Until the End of Study | 24 months approximately | — |
| Objective Response Rate (ORR) at the End of Treatment (EOT) | 6 months approximately | The ORR at EOT was defined as the proportion of patients with Complete Response (CR) or Partial response (PR) based on the response achieved at the EOT Visit/early treatment discontinuation visit. |
| Event-free Survival (EFS) at 12 and 24 Months | 24 months approximately | As many patients had their data censored, due to completing the study without disease progression, death due to any cause, or the start of a new anti-lymphoma treatment, the probability of EFS (%) was used. |
| Time to Next Anti-lymphoma Treatment (TTNT) | 24 months approximately | As many patients had their data censored, due to completing the study without needing to receive another anti-lymphoma treatment, the Probability of TTNT (%) was used. Time to next anti-lymphoma treatment survival % estimate was the estimated probability that a patient remained TTNT-free up to the specified point in time. |
| Overall Survival at 12 and 24 Months | 24 months approximately | As many patients had their data censored, due to completing the study without death from any cause, the probability of OS (%) was used. |
| Anti-tafasitamab Antibodies Formation | 12 months approximately | — |
| Progression-free Survival (PFS) at 12 and 24 Months | 24 months approximately | As many patients had their data censored, due to completing the study without disease progression or death due to any cause, the probability of PFS (%) was used. |
Countries
Austria, Belgium, Czechia, France, Germany, Italy, Portugal, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A Tafasitamab in addition to R-CHOP
Tafasitamab: Six 21-day cycles of tafasitamab (12 mg/kg intravenously, on Day 1, 8 and 15) in addition to R-CHOP | 33 |
| Arm B Tafasitamab plus lenalidomide in addition to R-CHOP
Tafasitamab plus lenalidomide: Six 21-day cycles of tafasitamab (12 mg/kg intravenously, on Day 1, 8 and 15) plus lenalidomide (starting dose 25 mg orally, on Day 1-10) in addition to R-CHOP | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Progressive disease | 1 | 0 |
| Overall Study | Progressive disease, joined another trial | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Arm A | Total | Arm B |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 11.64 | 62.6 years STANDARD_DEVIATION 11.96 | 61.4 years STANDARD_DEVIATION 12.34 |
| Age, Customized 18-64 years | 16 Participants | 33 Participants | 17 Participants |
| Age, Customized 65-84 years | 16 Participants | 32 Participants | 16 Participants |
| Age, Customized Greater than or equal to 85 years | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 31 Participants | 64 Participants | 33 Participants |
| Sex: Female, Male Female | 18 Participants | 38 Participants | 20 Participants |
| Sex: Female, Male Male | 15 Participants | 28 Participants | 13 Participants |
| Weight at Baseline (kg) | 73.03 kg STANDARD_DEVIATION 16.375 | 75.15 kg STANDARD_DEVIATION 16.213 | 77.27 kg STANDARD_DEVIATION 16.016 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 33 | 2 / 33 |
| other Total, other adverse events | 31 / 33 | 32 / 33 |
| serious Total, serious adverse events | 14 / 33 | 17 / 33 |
Outcome results
Primary
Incidence and Severity of Treatment-emergent Adverse Events (TEAEs)
Time frame: 6 months approximately
Population: No participants in the Arm A Group were assessed for the Patients with TEAE related to Lenalidomide only row, since they did not receive Lenalidomide.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any TEAE | 33 Participants |
| Arm A | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with TEAE related to R-CHOP only | 29 Participants |
| Arm A | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with TEAE related to Tafasitamab only | 9 Participants |
| Arm A | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any grade ≥3 TEAE | 27 Participants |
| Arm A | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any serious TEAE | 14 Participants |
| Arm A | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any study treatment-related TEAE | 31 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any grade ≥3 TEAE | 30 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any serious TEAE | 17 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any TEAE | 33 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with any study treatment-related TEAE | 32 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with TEAE related to Tafasitamab only | 5 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with TEAE related to Lenalidomide only | 16 Participants |
| Arm B | Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Patients with TEAE related to R-CHOP only | 23 Participants |
Secondary
Anti-tafasitamab Antibodies Formation
Time frame: 12 months approximately
Population: One patient in the Tafasitamab in addition to R-CHOP arm (Arm A) was missing a baseline sample and therefore could not be included in this analysis. In addition, no post-baseline evaluation was available for one patient in Arm A and one patient in Arm B hence the number of analyzed participants differs from overall.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Anti-tafasitamab Antibodies Formation | Patients without anti-tafasitamab antibodies after start of treatment | 30 Participants |
| Arm A | Anti-tafasitamab Antibodies Formation | Patients with treatment-induced anti-tafasitamab antibodies | 0 Participants |
| Arm A | Anti-tafasitamab Antibodies Formation | Patients with anti-tafasitamab antibodies after the start of treatment | 1 Participants |
| Arm A | Anti-tafasitamab Antibodies Formation | Patients with treatment-boosted anti-tafasitamab antibodies | 0 Participants |
| Arm A | Anti-tafasitamab Antibodies Formation | Patients with pre-existing anti-tafasitamab antibodies | 1 Participants |
| Arm B | Anti-tafasitamab Antibodies Formation | Patients with treatment-boosted anti-tafasitamab antibodies | 0 Participants |
| Arm B | Anti-tafasitamab Antibodies Formation | Patients with pre-existing anti-tafasitamab antibodies | 0 Participants |
| Arm B | Anti-tafasitamab Antibodies Formation | Patients without anti-tafasitamab antibodies after start of treatment | 32 Participants |
| Arm B | Anti-tafasitamab Antibodies Formation | Patients with anti-tafasitamab antibodies after the start of treatment | 0 Participants |
| Arm B | Anti-tafasitamab Antibodies Formation | Patients with treatment-induced anti-tafasitamab antibodies | 0 Participants |
Secondary
Best Objective Response Rate (ORR) Until the End of Study (EOS)
The best ORR was defined as the proportion of patients with Complete Response (CR) or Partial Response (PR) as the best response until the EOS.
Time frame: 24 months approximately
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Best Objective Response Rate (ORR) Until the End of Study (EOS) | 30 Participants |
| Arm B | Best Objective Response Rate (ORR) Until the End of Study (EOS) | 31 Participants |
Secondary
Event-free Survival (EFS) at 12 and 24 Months
As many patients had their data censored, due to completing the study without disease progression, death due to any cause, or the start of a new anti-lymphoma treatment, the probability of EFS (%) was used.
Time frame: 24 months approximately
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Event-free Survival (EFS) at 12 and 24 Months | Probability of EFS (%) at 12 months | 77.4 percent |
| Arm A | Event-free Survival (EFS) at 12 and 24 Months | Probability of EFS (%) at 24 months | 67.7 percent |
| Arm B | Event-free Survival (EFS) at 12 and 24 Months | Probability of EFS (%) at 12 months | 68.0 percent |
| Arm B | Event-free Survival (EFS) at 12 and 24 Months | Probability of EFS (%) at 24 months | 68.0 percent |
Secondary
Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period
Time frame: 18 months for non-treatment emergent adverse events, 6 months for treatment emergent adverse events
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | Patients with at least 1 AE in the FU period | 26 Participants |
| Arm A | Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | Patients with a Grade ≥3 TEAE in the FU period | 9 Participants |
| Arm A | Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | Patients with at least 1 treatment related AE in the FU period | 9 Participants |
| Arm B | Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | Patients with at least 1 AE in the FU period | 26 Participants |
| Arm B | Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | Patients with a Grade ≥3 TEAE in the FU period | 13 Participants |
| Arm B | Incidence and Severity of Adverse Events (AEs) in the Follow-up (FU) Period | Patients with at least 1 treatment related AE in the FU period | 7 Participants |
Secondary
Metabolic, PET-negative Complete Response (CR) Rate at the End of Treatment
Time frame: 6 months approximately
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Metabolic, PET-negative Complete Response (CR) Rate at the End of Treatment | 24 Participants |
| Arm B | Metabolic, PET-negative Complete Response (CR) Rate at the End of Treatment | 22 Participants |
Secondary
Metabolic, PET-negative Complete Response (CR) Rate Until the End of Study
Time frame: 24 months approximately
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Metabolic, PET-negative Complete Response (CR) Rate Until the End of Study | 28 Participants |
| Arm B | Metabolic, PET-negative Complete Response (CR) Rate Until the End of Study | 23 Participants |
Secondary
Objective Response Rate (ORR) at the End of Treatment (EOT)
The ORR at EOT was defined as the proportion of patients with Complete Response (CR) or Partial response (PR) based on the response achieved at the EOT Visit/early treatment discontinuation visit.
Time frame: 6 months approximately
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Objective Response Rate (ORR) at the End of Treatment (EOT) | 25 Participants |
| Arm B | Objective Response Rate (ORR) at the End of Treatment (EOT) | 27 Participants |
Secondary
Overall Survival at 12 and 24 Months
As many patients had their data censored, due to completing the study without death from any cause, the probability of OS (%) was used.
Time frame: 24 months approximately
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Overall Survival at 12 and 24 Months | Probability of OS (%) at 12 months | 90.3 percent |
| Arm A | Overall Survival at 12 and 24 Months | Probability of OS (%) at 24 months | 90.3 percent |
| Arm B | Overall Survival at 12 and 24 Months | Probability of OS (%) at 12 months | 93.8 percent |
| Arm B | Overall Survival at 12 and 24 Months | Probability of OS (%) at 24 months | 93.8 percent |
Secondary
Progression-free Survival (PFS) at 12 and 24 Months
As many patients had their data censored, due to completing the study without disease progression or death due to any cause, the probability of PFS (%) was used.
Time frame: 24 months approximately
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Progression-free Survival (PFS) at 12 and 24 Months | Probability of PFS (%) at 12 months | 83.1 percent |
| Arm A | Progression-free Survival (PFS) at 12 and 24 Months | Probability of PFS (%) at 24 months | 72.7 percent |
| Arm B | Progression-free Survival (PFS) at 12 and 24 Months | Probability of PFS (%) at 12 months | 76.8 percent |
| Arm B | Progression-free Survival (PFS) at 12 and 24 Months | Probability of PFS (%) at 24 months | 76.8 percent |
Secondary
Time to Next Anti-lymphoma Treatment (TTNT)
As many patients had their data censored, due to completing the study without needing to receive another anti-lymphoma treatment, the Probability of TTNT (%) was used. Time to next anti-lymphoma treatment survival % estimate was the estimated probability that a patient remained TTNT-free up to the specified point in time.
Time frame: 24 months approximately
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Time to Next Anti-lymphoma Treatment (TTNT) | Probability of TTNT (%) at 12 months | 77.4 percent |
| Arm A | Time to Next Anti-lymphoma Treatment (TTNT) | Probability of TTNT (%) at 24 months | 71.0 percent |
| Arm B | Time to Next Anti-lymphoma Treatment (TTNT) | Probability of TTNT (%) at 12 months | 71.9 percent |
| Arm B | Time to Next Anti-lymphoma Treatment (TTNT) | Probability of TTNT (%) at 24 months | 68.8 percent |