Study of Tafasitamab and Lenalinomide Associated to Rituximab in Frontline Diffuse Large B-Cell Lymphoma Patients of 80 y/o or Older
- Conditions
- DLBCL
- Interventions
- Registration Number
- NCT04974216
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 71
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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description R-Lena-Tafa Tafasitamab 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 R-Lena-Tafa Lenalidomide 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 R-Lena-Tafa Rituximab 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
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Progression free survival (PFS) 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 local assessment 12 months (12 cycles of 28 days = end of treatment) LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria
Overall survival (OS) 2 years Complete Metabolic Response (CMR) by central assessment 12 months (12 cycles of 28 days = end of treatment) CENTRAL ASSESSMENT
Complete Metabolic Response (CMR) by local assessment 12 months (12 cycles of 28 days = end of treatment) LOCAL ASSESSMENT
Progression free survival (PFS) of patients who switched to RminiCHOP 3 years Overall survival (OS) of patients who switched to RminiCHOP 3 years Overall Response Rate (ORR) by central assessment 12 months (12 cycles of 28 days = end of treatment) CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria
Trial Locations
- Locations (15)
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
🇫🇷Vandoeuvre les Nancy, France