Study of Tafasitamab and Lenalinomide Associated to Rituximab in Frontline Diffuse Large B-Cell Lymphoma Patients of 80 y/o or Older
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| 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:
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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 [3 months (3 cycles of 28 days)]
CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria
- Complete Metabolic Response (CMR) by local assessment [3 months (3 cycles of 28 days)]
LOCAL ASSESSMENT
- Complete Metabolic Response (CMR) by central assessment [3 months (3 cycles of 28 days)]
CENTRAL ASSESSMENT
- Complete Metabolic Response (CMR) by local assessment [6 months (6 cycles of 28 days)]
LOCAL ASSESSMENT
- Complete Metabolic Response (CMR) by central assessment [6 months (6 cycles of 28 days)]
CENTRAL ASSESSMENT
- Complete Metabolic Response (CMR) by local assessment [12 months (12 cycles of 28 days = end of treatment)]
LOCAL ASSESSMENT
- Complete Metabolic Response (CMR) by central assessment [12 months (12 cycles of 28 days = end of treatment)]
CENTRAL ASSESSMENT
- Overall Response Rate (ORR) by local assessment [6 months (6 cycles of 28 days)]
LOCAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria
- Overall Response Rate (ORR) by central assessment [6 months (6 cycles of 28 days)]
CENTRAL ASSESSMENT : Complete Metabolic Response + Partial Metabolic Response based according to Lugano Response Criteria
- 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 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
- Progression free survival (PFS) of patients who switched to RminiCHOP [3 years]
- Overall survival (OS) of patients who switched to RminiCHOP [3 years]
Eligibility Criteria
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:
-
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinique Universitaire Saint LUC | Brussels | Belgium | ||
| 2 | CHU de Liège | Liège | Belgium | ||
| 3 | CHRU Mont Godinne | Yvoir | Belgium | ||
| 4 | CHU de Bordeaux - Hôpital Haut Lévêque | Bordeaux | France | ||
| 5 | Institut Bergonié - Bordeaux | Bordeaux | France | ||
| 6 | CH Saint Vincent de Paul | Lille | France | ||
| 7 | CHRU de LILLE - Claude Huriez | Lille | France | ||
| 8 | Chu de Limoges - Hopital Dupuytren | Limoges | France | ||
| 9 | CHU de Nantes - Hôtel Dieu | Nantes | France | ||
| 10 | Centre Antoine Lacassagne | Nice | France | ||
| 11 | APHP - Hôpital Saint Louis | Paris | France | ||
| 12 | Centre Henri Becquerel | Rouen | France | ||
| 13 | Centre René Huguenin - Institut Curie | Saint-Cloud | France | ||
| 14 | Institut de Cancérologie de la Loire Lucien Neuwirth | Saint-Priest-en-Jarez | France | 42270 | |
| 15 | CHU Brabois | Vandoeuvre les Nancy | France |
Sponsors and Collaborators
- The Lymphoma Academic Research Organisation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VERLen