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

DLBCL Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04974216
• Other study ID #: VERLen
• Status: Recruiting
• Phase: Phase 2
• Start date: December 20, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 71
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 80 Years and older

Eligibility

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

Related Conditions & MeSH terms

• DLBCL
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Tafasitamab
Administration : IV at 12mg/Kg C1 to C3: D1, D8, D15, D22 C4 to C6: D1, D15 C7 to C12: D1
• Lenalidomide
Oral administration: hard capsule C1 to C6: 20mg/day C7 to C12: 15mg/day
• Rituximab
Administration: IV at 375mg/m2 C1 to C6: D1

Locations

Country	Name	City	State
Belgium	Clinique Universitaire Saint LUC	Brussels
Belgium	CHU de Liège	Liège
Belgium	CHRU Mont Godinne	Yvoir
France	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	Vandoeuvre les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Serious Adverse Events (SAE) of patients treated with lenalidomide and tafasitamab		13 months
Secondary	Number of SAE of patients who switched to RminiCHOP		7 months
Secondary	Progression free survival (PFS)		2 years
Secondary	Overall survival (OS)		2 years
Secondary	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)
Secondary	Complete Metabolic Response (CMR) by local assessment	LOCAL ASSESSMENT	3 months (3 cycles of 28 days)
Secondary	Complete Metabolic Response (CMR) by central assessment	CENTRAL ASSESSMENT	3 months (3 cycles of 28 days)
Secondary	Complete Metabolic Response (CMR) by local assessment	LOCAL ASSESSMENT	6 months (6 cycles of 28 days)
Secondary	Complete Metabolic Response (CMR) by central assessment	CENTRAL ASSESSMENT	6 months (6 cycles of 28 days)
Secondary	Complete Metabolic Response (CMR) by local assessment	LOCAL ASSESSMENT	12 months (12 cycles of 28 days = end of treatment)
Secondary	Complete Metabolic Response (CMR) by central assessment	CENTRAL ASSESSMENT	12 months (12 cycles of 28 days = end of treatment)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Progression free survival (PFS) of patients who switched to RminiCHOP		3 years
Secondary	Overall survival (OS) of patients who switched to RminiCHOP		3 years