| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Diffuse Large B Cells Lymphoma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10012855 |
| E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of tafasitamab (anti-CD19 antibody) and lenalidomide associated with rituximab (R-Tafa-Len) in elderly patients as assessed by the Overall Response Rate (ORR) after 3 cycles of treatment or at permanent treatment discontinuation, whichever occurs first. |
|
| E.2.2 | Secondary objectives of the trial |
Assess safety of lena and tafa and of R-Len-Tafa as measured by the 2y-PFS and 2y-OS
Evaluate ORR after 3cycles or at permanent treatment discontinuation, whichever occurs first, as assessed by central review of PET-CT according to Lugano Response Criteria
Evaluated CMR rate after 3cycles or at permanent treatment discontinuation, whichever occurs first, based on investigator disease and central assessment
Evaluate CMR+ORR after 6cycles or permanent treatment discontinuation, whichever occurs first, and at EoT (Treatment completion or permanent treatment discontinuation), according to Lugano Response Criteria, based on investigator disease assessment and central assessment
Evaluate the safety of patients who switch to R-miniCHOP based on tafasitamab and/or lenalidomide related SAEs and deaths
Evaluate, the response to RminiCHOP, PFS and the OS of patients who switch to R-miniCHOP
Evaluate geriatric quality of life assessments at enrollment, after 3 cycles, and at EoT |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patient with histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2017) including all clinical subtypes (primary mediastinal, intravascular, etc…), with all aaIPI. 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
OR
Previously untreated high-grade B-cell lymphoma |
|
| E.4 | Principal 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 MDRD or 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 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)
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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall metabolic Response Rate (ORR: CMR+PMR) after 3 cycles of treatment (or at permanent treatment discontinuation, whichever occurs first) according to local assessment based on Lugano Response Criteria. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| after 3 cycles of treatment or at permanent treatment discontinuation |
|
| E.5.2 | Secondary end point(s) |
• PET-CT result according to local and central review
• Metabolic response rates according to Lugano classification
• Overall Survival (OS)
• Progression Free Survival (PFS)
• Duration of Response (DoR)
• Quality of Life (QoL)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PET-CT: After 3 cycles, 6 cycles and at the end of treatment (complete or at permanent treatment discontinuation)
Metabolic response rates according to Lugano classification :
-after 3, 6 or 12 cycles or at permanent treatment discontinuation whichever occurs first.
OS : From enrollment to the date of death from any cause. Alive patients will be censored at the date of last contact.
PFS : From enrollment into the study to the first observation of documented disease progression or death due to any cause.
If a patient has not progressed or died, PFS will be censored at the date of tumor assessment.
DoR : from the time of first CMR or PMR based on investigator disease assessment to the date of first documented disease progression, relapse or death
QoL : enrollment, after 3cycles, EoT |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS : patients will be followed until the last patient included will have been followed up for three years after his last intake of study medication |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
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