VERLEN - Phase II, Open-Label Study evaluating efficacy of Lenalidomide and Tafasitamab combination associated to Rituximab in frontline Diffuse Large B-Cell Lymphoma Patients of 80 y/o or older

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lysarc

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

23 Dec 2021 → ongoing

Decision date (initial)

2024-01-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-507286-25-00

EudraCT number

2020-004977-38

ClinicalTrials.gov

NCT04974216

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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.

Secondary objectives 12

1. To assess safety of lenalidomide and tafasitamab in the context of patients treated by rituximab
2. To assess the efficacy of R-Len-Tafa as measured by the 2y-Progression Free Survival (PFS) and 2y-Overall Survival (OS)
3. 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
4. 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
5. 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
6. To evaluate the safety of patients who switch to R-miniCHOP based on tafasitamab and/or lenalidomide related SAEs and deaths
7. To evaluate, the response to RminiCHOP, PFS and the OS of patients who switch to R-miniCHOP
8. To evaluate geriatric quality of life assessments at enrollment, after 3 cycles, and at EoT
9. Influence of ctDNA as an early outcome predictor of therapeutic response.
10. Extensive analyse of the tumor immune microenvironment (lenalidomide immunomodulation and Tafasitamab-induced immune-responses)
11. Analysis of the immune response in the blood
12. Genomic characterization of the tumor

Conditions and MedDRA coding

Diffuse Large B-Cell Lymphoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patient must understand and voluntarily sign an Informed Consent Form prior to any study-specific assessments/procedures being conducted
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 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
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. ECOG 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 16

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 <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.
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR encompasses patients that reach Complete Metabolic Response or Partial Metabolic Response based on investigator disease assessment according to Lugano Response Criteria.

Secondary endpoints 6

1. Central review of PET-CT according to Lugano Response Criteria
2. Complete Metabolic response (CMR) rates based on investigator disease assessment and central assessment
3. Overall Survival (OS)
4. Quality of Life (QoL)
5. Progression Free Survival (PFS)
6. Assess safety of lenalidomide and tafasitamab in the context of patients treated by rituximab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lysarc

Sponsor organisation

LYSARC

Address

2d Lyon Sud Batiment

City

Pierre Benite

Postcode

69495

Country

France

Scientific contact point

Organisation

LYSARC

Contact name

Benoit TESSOULIN

Public contact point

Organisation

LYSARC

Contact name

Benoit TESSOULIN

Locations

2 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications