Study of Tafasitamab and Lenalinomide Associated to Rituximab in Frontline Diffuse Large B-Cell Lymphoma Patients of 80 y/o or Older

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II, Open-Label Study Evaluating Efficacy of Tafasitamab and Lenalinomide Associated to Rituximab in Frontline Diffuse Large B-Cell Lymphoma Patients of 80 y/o or Older

Conditions
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DLBCL

Intervention / Treatment
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* Drug: Tafasitamab
* Drug: Lenalidomide
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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: Any other histological type of lymphoma, Burkitt included Any history of treated or non-treated Small-B cell lymphoma prior Aggressive B Cell lymphoma diagnosis Central nervous system or meningeal involvement by lymphoma Any serious active disease (according to the investigator's decision) Poor renal function (calculated Cockcroft-Gault creatinine clearance < 30 ml/min) Poor hepatic function (total bilirubin level >30 μmol/l, transaminases >2.5 upper normal limits) unless these abnormalities are related to lymphoma 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) 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 Treatment with any investigational drug within 30 days prior to prephase treatment and during the study 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) Prior treatment with anti-CD20/anti-CD19 monoclonal antibody or alemtuzumab within 3 months prior to prephase treatment Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide Contra-indication to highly dosed glucocorticoid (60 mg/m2/d) Neuropathy ≥ Grade 2 or painful Patient deprived of his/her liberty by a judicial or administrative decision Adult patient under legal protection

Ages Eligible for Study
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Minimum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-Lena-Tafa<br>12 cycles of 28 days. From C1 to C6 : rituximab + tafasitamab + lenalidomide and from C7 to C12: tafasitamab and lenalidomide Patients with Progressive Disease or Stable Disease after 3 cycles should start a conventional chemotherapy (rituximab + cyclophosphamide + adriamycine + vincristine + prednisone R-miniCHOP) at Investigator's discretion according to local practices | Drug: Tafasitamab<br>* Administration : IV at 12mg/Kg C1 to C3: D1, D8, D15, D22 C4 to C6: D1, D15 C7 to C12: D1<br>* Other names: MOR208;Drug: Lenalidomide<br>* Oral administration: hard capsule C1 to C6: 20mg/day C7 to C12: 15mg/day<br>Drug: Rituximab<br>* Administration: IV at 375mg/m2 C1 to C6: D1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) by local assessment | LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria | 3 months (3 cycles of 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria | 3 months (3 cycles of 28 days) | 
| Complete Metabolic Response (CMR) by local assessment | LOCAL ASSESSMENT | 3 months (3 cycles of 28 days) | 
| Complete Metabolic Response (CMR) by central assessment | CENTRAL ASSESSMENT | 3 months (3 cycles of 28 days) | 
| Complete Metabolic Response (CMR) by local assessment | LOCAL ASSESSMENT | 6 months (6 cycles of 28 days) | 
| Complete Metabolic Response (CMR) by central assessment | CENTRAL ASSESSMENT | 6 months (6 cycles of 28 days) | 
| Complete Metabolic Response (CMR) by local assessment | LOCAL ASSESSMENT | 12 months (12 cycles of 28 days = end of treatment) | 
| Complete Metabolic Response (CMR) by central assessment | CENTRAL ASSESSMENT | 12 months (12 cycles of 28 days = end of treatment) | 
| Overall Response Rate (ORR) by local assessment | LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria | 6 months (6 cycles of 28 days) | 
| Overall Response Rate (ORR) by central assessment | CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria | 6 months (6 cycles of 28 days) | 
| Overall Response Rate (ORR) by local assessment | LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria | 12 months (12 cycles of 28 days = end of treatment) | 
| Overall Response Rate (ORR) by central assessment | CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria | 12 months (12 cycles of 28 days = end of treatment) | 
| Progression free survival (PFS) of patients who switched to RminiCHOP |  | 3 years | 
| Overall survival (OS) of patients who switched to RminiCHOP |  | 3 years |