DLBCL
Conditions
Brief summary
This study evaluate the efficacy of Tafasitamab and Lenalinomide associated to Rituximab in elderly patients with frontline Diffuse Large B-Cell Lymphoma as assessed by the Overall Response Rate (ORR) after 3 cycles of treatment according to Lugano Response Criteria.
Detailed description
This study is an open-label, multi-centric, phase II study designed to evaluate the efficacy of Tafasitamab and Lenalinomide associated to Rituximab in elderly patients with frontline Diffuse Large B-Cell Lymphoma as assessed by the Overall Response Rate (ORR) after 3 cycles of treatment according to Lugano Response Criteria. After a screening phase, eligible patients will be enrolled and start the prephase treatment with vincristine and prednisone before day 1 of cycle 1 of the experimental drugs. Patients with Progressive Disease or Stable Disease after 3 cycles should start a conventional chemotherapy (R-miniCHOP) at Investigator's discretion and will remain in the study.
Interventions
DRUGTafasitamab
Administration : IV at 12mg/Kg C1 to C3: D1, D8, D15, D22 C4 to C6: D1, D15 C7 to C12: D1
DRUGLenalidomide
Oral administration: hard capsule C1 to C6: 20mg/day C7 to C12: 15mg/day
DRUGRituximab
Administration: IV at 375mg/m2 C1 to C6: D1
Sponsors
The Lymphoma Academic Research Organisation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
80 Years to No maximum
Healthy volunteers
No
Inclusion criteria
2.Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2017) including all clinical subtypes (primary mediastinal, intravascular, etc…), with all International Prognostic Index (IPI). May also be enrolled the following malignancies: * De Novo transformed DLBCL from low grade lymphoma (Follicular, other...) and DLBCL associated with some small cell infiltration in bone marrow or lymph node. * High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements * High-grade B-cell lymphoma, Not Otherwise Specified (NOS) * Follicular lymphoma grade 3B 3.Positron-Emission Tomography (PET)-positive disease 4.Previously untreated high-grade B-cell lymphoma 5.Aged ≥ 80 years old at the time of signing the informed consent form (ICF) 6.Ann Arbor stage I, II, III or IV 7.Eastern Cooperative Oncology Group (ECO)G performance status ≤ 2 8.With a minimum life expectancy of 3 months 9.Male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 4 months following study drug discontinuation, even if they have undergone a successful vasectomy 10. Patients should be able to receive R-miniCHOP regimen (left ventricular ejection fraction \> 50% and good general condition, according to investigator's judgment) 11. Patients should be able to receive adequate prophylaxis and/or therapy for thromboembolic events (aspirin or low molecular weight heparin) 12. Patient covered by any social security system (France)
Exclusion criteria
1. Any other histological type of lymphoma, Burkitt included 2. Any history of treated or non-treated Small-B cell lymphoma prior Aggressive B Cell lymphoma diagnosis 3. Central nervous system or meningeal involvement by lymphoma 4. Any serious active disease (according to the investigator's decision) 5. Poor renal function (calculated Cockcroft-Gault creatinine clearance \< 30 ml/min) 6. Poor hepatic function (total bilirubin level \>30 μmol/l, transaminases \>2.5 upper normal limits) unless these abnormalities are related to lymphoma 7. Poor bone marrow reserve as defined by neutrophils \<1.5 G/l or platelets \<100 G/l, unless related to bone marrow infiltration by lymphoma cells (Bone Marrow Aspiration will be mandatory in case of severe cytopenias prior inclusion) 8. Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score ≤7, and a prostate specific antigen (PSA) ≤10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (i.e., prostatectomy or radiotherapy) 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or \<1 ng/mL if they did not undergo prostatectomy 9. Treatment with any investigational drug within 30 days prior to prephase treatment and during the study 10. Known HIV, active Hepatitis C Virus (HCV) infection or positive Hepatitis B Virus (HBV) test within 4 weeks before enrollment (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative) 11. Prior treatment with anti-CD20/anti-CD19 monoclonal antibody or alemtuzumab within 3 months prior to prephase treatment 12. Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide 13. Contra-indication to highly dosed glucocorticoid (60 mg/m2/d) 14. Neuropathy ≥ Grade 2 or painful 15. Patient deprived of his/her liberty by a judicial or administrative decision 16. Adult patient under legal protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) by local assessment | 3 months (3 cycles of 28 days) | LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Adverse Events (SAE) of patients treated with lenalidomide and tafasitamab | 13 months | — |
| Number of SAE of patients who switched to RminiCHOP | 7 months | — |
| Progression free survival (PFS) | 2 years | — |
| Overall survival (OS) | 2 years | — |
| Overall Response Rate (ORR) by central assessment | 3 months (3 cycles of 28 days) | CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria |
| Complete Metabolic Response (CMR) by local assessment | 3 months (3 cycles of 28 days) | LOCAL ASSESSMENT |
| Complete Metabolic Response (CMR) by central assessment | 3 months (3 cycles of 28 days) | CENTRAL ASSESSMENT |
| Overall Response Rate (ORR) by local assessment | 6 months (6 cycles of 28 days) | LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria |
| Progression free survival (PFS) of patients who switched to RminiCHOP | 3 years | — |
| Overall survival (OS) of patients who switched to RminiCHOP | 3 years | — |
Countries
Belgium, France
Outcome results
None listed