Lenalidomide for Diffuse large B-cell lymphoma

Inclusion criteria

• {"criterion_text":"-Patient must understand and voluntarily sign an Informed Consent Form prior to any study-specific assessments/procedures being conducted"}
• {"criterion_text":"-Patients should be able to receive R-miniCHOP regimen (left ventricular ejection fraction > 50% and good general condition, according to investigator’s judgment)"}
• {"criterion_text":"-Patients should be able to receive adequate prophylaxis and/or therapy for thromboembolic events (aspirin or low molecular weight heparin)"}
• {"criterion_text":"-Patient covered by any social security system (France)"}
• {"criterion_text":"-Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2017) including all clinical subtypes (primary mediastinal, intravascular, etc…), with all 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, NOS • Follicular lymphoma grade 3B"}
• {"criterion_text":"-Positron-Emission Tomography (PET)-positive disease"}
• {"criterion_text":"-Previously untreated high-grade B-cell lymphoma"}
• {"criterion_text":"-Aged ≥ 80 years old at the time of signing the informed consent form (ICF)"}
• {"criterion_text":"-Ann Arbor stage I, II, III or IV"}
• {"criterion_text":"-ECOG performance status ≤ 2"}
• {"criterion_text":"-With a minimum life expectancy of 3 months"}
• {"criterion_text":"-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"}

Exclusion criteria

• {"criterion_text":"-Any other histological type of lymphoma, Burkitt included"}
• {"criterion_text":"-Known HIV, active HCV infection or positive 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)"}
• {"criterion_text":"-Prior treatment with anti-CD20/anti-CD19 monoclonal antibody or alemtuzumab within 3 months prior to prephase treatment"}
• {"criterion_text":"-Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide"}
• {"criterion_text":"-Contra-indication to highly dosed glucocorticoid (60 mg/m2/d)"}
• {"criterion_text":"-Neuropathy ≥ Grade 2 or painful"}
• {"criterion_text":"-Patient deprived of his/her liberty by a judicial or administrative decision"}
• {"criterion_text":"-Adult patient under legal protection"}
• {"criterion_text":"-Any history of treated or non-treated Small-B cell lymphoma prior Aggressive B Cell lymphoma diagnosis"}
• {"criterion_text":"-Central nervous system or meningeal involvement by lymphoma"}
• {"criterion_text":"-Any serious active disease (according to the investigator’s decision)"}
• {"criterion_text":"-Poor renal function (calculated Cockcroft-Gault creatinine clearance < 30 ml/min)"}
• {"criterion_text":"-Poor hepatic function (total bilirubin level >30 μmol/l, transaminases >2.5 upper normal limits) unless these abnormalities are related to lymphoma"}
• {"criterion_text":"-Poor bone marrow reserve as defined by neutrophils <1G/L or platelets <100G/L, even if there is bone marrow infiltration by lymphoma. A Bone Marrow Aspiration will be mandatory prior inclusion for patients with neutrophils <1.5 G/L or Hemoglobin <9g/dL in order to exclude patients with concomitant myelodysplasia."}
• {"criterion_text":"-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"}
• {"criterion_text":"-Treatment with any investigational drug within 30 days prior to prephase treatment and during the study"}

Primary endpoints

• {"endpoint_text":"-ORR encompasses patients that reach Complete Metabolic Response or Partial Metabolic Response based on investigator disease assessment according to Lugano Response Criteria.","definition_or_measurement_approach":"Overall Response Rate (ORR) after 3 cycles of treatment or at permanent treatment discontinuation (whichever occurs first), assessed by investigator disease assessment using Lugano Response Criteria."}

Secondary endpoints

• {"endpoint_text":"-Central review of PET-CT according to Lugano Response Criteria","definition_or_measurement_approach":"Central review of PET-CT scans using Lugano Response Criteria (central radiological/pathological review)."}
• {"endpoint_text":"-Complete Metabolic response (CMR) rates based on investigator disease assessment and central assessment","definition_or_measurement_approach":"CMR rates assessed both by investigator disease assessment and by central review, after specified cycles (e.g., after 3 cycles) according to Lugano Criteria."}
• {"endpoint_text":"-Overall Survival (OS)","definition_or_measurement_approach":"Time-to-event overall survival (may include 2-year OS assessment as specified in objectives)."}
• {"endpoint_text":"-Quality of Life (QoL)","definition_or_measurement_approach":"Geriatric quality of life assessments at enrollment, after 3 cycles, at End of Treatment and every 6 months for 2 years (using specified QoL instruments)."}
• {"endpoint_text":"-Progression Free Survival (PFS)","definition_or_measurement_approach":"Time-to-progression or death; objectives specify 2-year PFS assessment."}
• {"endpoint_text":"-Assess safety of lenalidomide and tafasitamab in the context of patients treated by rituximab","definition_or_measurement_approach":"Safety assessment via adverse events, serious adverse events and deaths related to tafasitamab and/or lenalidomide in patients receiving rituximab."}

Other endpoints

• {"endpoint_text":"-To assess safety of lenalidomide and tafasitamab in the context of patients treated by rituximab","definition_or_measurement_approach":"Safety endpoints by AE/SAE reporting and relatedness to study drugs in the rituximab context."}
• {"endpoint_text":"-To assess the efficacy of R-Len-Tafa as measured by the 2y-Progression Free Survival (PFS) and 2y-Overall Survival (OS)","definition_or_measurement_approach":"2-year PFS and 2-year OS time-to-event analyses."}
• {"endpoint_text":"-To evaluate ORR after 3 cycles or at permanent treatment discontinuation, whichever occurs first, as assessed by central review of PET-CT according to Lugano Response Criteria","definition_or_measurement_approach":"Central review of PET-CT using Lugano criteria to determine ORR at 3 cycles or at discontinuation."}
• {"endpoint_text":"-To evaluated Complete Metabolic Response (CMR) rate after 3 cycles or at permanent treatment discontinuation, whichever occurs first, based on investigator disease assessment and central assessment","definition_or_measurement_approach":"CMR rates at 3 cycles or at discontinuation assessed by investigator and central review using Lugano criteria."}
• {"endpoint_text":"-To evaluate the CMR and ORR after 6 cycles or permanent treatment discontinuation, whichever occurs first, and at End of Treatment (EoT = Treatment completion or permanent treatment discontinuation), according to Lugano Response Criteria, based on investigator disease assessment and central assessment","definition_or_measurement_approach":"CMR and ORR at 6 cycles and at EoT assessed by investigator and central review per Lugano criteria."}
• {"endpoint_text":"-To evaluate the safety of patients who switch to R-miniCHOP based on tafasitamab and/or lenalidomide related SAEs and deaths","definition_or_measurement_approach":"Safety monitoring of patients switching to standard R-miniCHOP, recording SAEs and deaths related to study drugs."}
• {"endpoint_text":"-To evaluate, the response to RminiCHOP, PFS and the OS of patients who switch to R-miniCHOP","definition_or_measurement_approach":"Response rates, PFS and OS among patients who switch to R-miniCHOP."}
• {"endpoint_text":"-To evaluate geriatric quality of life assessments at enrollment, after 3 cycles, and at EoT","definition_or_measurement_approach":"QoL assessments at specified timepoints (enrollment, after 3 cycles, EoT, and every 6 months for 2 years)."}
• {"endpoint_text":"-Influence of ctDNA as an early outcome predictor of therapeutic response.","definition_or_measurement_approach":"Exploratory analysis of circulating tumor DNA (ctDNA) as an early predictor of response."}
• {"endpoint_text":"-Extensive analyse of the tumor immune microenvironment (lenalidomide immunomodulation and Tafasitamab-induced immune-responses)","definition_or_measurement_approach":"Exploratory immunological and microenvironment analyses of tumor tissue to assess immunomodulation and immune responses."}
• {"endpoint_text":"-Analysis of the immune response in the blood","definition_or_measurement_approach":"Peripheral blood immune response profiling."}
• {"endpoint_text":"-Genomic characterization of the tumor","definition_or_measurement_approach":"Genomic analyses of tumor tissue for characterization/exploratory endpoints."}

Belgium

Earliest CTIS Part Ii Submission Date

17-11-2023

Latest Decision Or Authorization Date

24-02-2025

Processing Time Days

465

Number Of Sites

5

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

08-12-2023

Latest Decision Or Authorization Date

11-03-2025

Processing Time Days

459

Number Of Sites

15

Number Of Participants

37

Primary sponsor

Full Name

LYSARC

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France