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

NCT ID: NCT04974216

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-20
• Study Completion Date: 2026-12-31

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.

Conditions

DLBCL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Tafasitamab

Intervention Type: DRUG

Administration : IV at 12mg/Kg C1 to C3: D1, D8, D15, D22 C4 to C6: D1, D15 C7 to C12: D1

Lenalidomide

Intervention Type: DRUG

Oral administration: hard capsule C1 to C6: 20mg/day C7 to C12: 15mg/day

Rituximab

Intervention Type: DRUG

Administration: IV at 375mg/m2 C1 to C6: D1

Interventions

Tafasitamab

Administration : IV at 12mg/Kg C1 to C3: D1, D8, D15, D22 C4 to C6: D1, D15 C7 to C12: D1

Intervention Type: DRUG

Lenalidomide

Oral administration: hard capsule C1 to C6: 20mg/day C7 to C12: 15mg/day

Intervention Type: DRUG

Rituximab

Administration: IV at 375mg/m2 C1 to C6: D1

Intervention Type: DRUG

Other Intervention Names

MOR208

Eligibility Criteria

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

• Minimum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinique Universitaire Saint LUC

Brussels, , Belgium

CHU de Liège

Liège, , Belgium

CHRU Mont Godinne

Yvoir, , Belgium

CHU de Bordeaux - Hôpital Haut Lévêque

Bordeaux, , France

Institut Bergonié - Bordeaux

Bordeaux, , France

CH Saint Vincent de Paul

Lille, , France

CHRU de LILLE - Claude Huriez

Lille, , France

Chu de Limoges - Hopital Dupuytren

Limoges, , France

CHU de Nantes - Hôtel Dieu

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

APHP - Hôpital Saint Louis

Paris, , France

Centre Henri Becquerel

Rouen, , France

Centre René Huguenin - Institut Curie

Saint-Cloud, , France

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, , France

CHU Brabois

Vandœuvre-lès-Nancy, , France

Countries

Belgium; France

Other Identifiers

VERLen

Identifier Type: -

Identifier Source: org_study_id