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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: DLBCL
• Intervention / Treatment: Drug: Tafasitamab; Drug: Lenalidomide; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Clinique Universitaire Saint LUC
  • Charleroi, Belgium, 6000
    • Grand Hôpital de Charleroi
  • La Louvière, Belgium, 7100
    • Chu Helora
  • Liège, Belgium
    • CHU de Liege
  • Yvoir, Belgium
    • CHRU Mont Godinne
• France
  • Avignon, France
    • Centre Hospitalier D Avignon
  • Bayonne, France
    • Centre Hospitalier de la Côte Basque
  • Besançon, France, 25030
    • Besancon University Hospital Center
  • Bordeaux, France
    • Institut Bergonié - Bordeaux
  • Bordeaux, France
    • CHU de Bordeaux - Hopital Haut Leveque
  • Corbeil-Essonnes, France
    • Centre Hospitalier Sud Francilien
  • La Roche-sur-Yon, France
    • Centre Hospitalier Departemental Vendee
  • Lille, France
    • CH Saint Vincent de Paul
  • Lille, France
    • CHRU de LILLE - Claude Huriez
  • Limoges, France
    • CHU de Limoges - Hopital Dupuytren
  • Nantes, France
    • CHU de Nantes - Hôtel Dieu
  • Paris, France
    • APHP - Hopital Saint Louis
  • Rouen, France
    • Centre Henri Becquerel
  • Saint-Priest-en-Jarez, France, 42270
    • Institut de Cancérologie de la Loire Lucien Neuwirth
  • Vandœuvre-lès-Nancy, France
    • CHU Brabois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 80 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: R-Lena-Tafa; 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; Administration : IV at 12mg/Kg C1 to C3: D1, D8, D15, D22 C4 to C6: D1, D15 C7 to C12: D1; Other Names: MOR208; Drug: Lenalidomide; Oral administration: hard capsule C1 to C6: 20mg/day C7 to C12: 15mg/day; Drug: Rituximab; Administration: IV at 375mg/m2 C1 to C6: D1

What is the study measuring?

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
Progression free survival (PFS)		2 years
Overall survival (OS)		2 years
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
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

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Actual): July 15, 2024
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Rituximab; tafasitamab
• Other Study ID Numbers: VERLen

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No