Primary CNS Lymphoma (PCNSL)Phase 2E-REVRINCT06931652
Study of Epcoritamab in R/R Primary Diffuse Large B-cell Lymphoma of the CNS Treated With Lenalidomide and Rituximab
A Phase 2 study testing Epcoritamab in people with Primary CNS Lymphoma (PCNSL), run by The Lymphoma Academic Research Organisation at 13 sites in France.
Trial summary
The purpose of this phase 2 study is to evaluate the efficacy and safety of epcoritamab in subjects with relapsed or refractory primary diffuse large B-cell lymphoma of the Central Nervous System treated with rituximab and lenalidomide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary CNS Lymphoma (PCNSL)
- What is being tested?
- Epcoritamab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 13 sitesFrance
- Study dates
- 22 Sep 2025to Jan 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject (or their legally acceptable representative/trusted person) who understand and voluntarily signs and dates an informed consent form prior to any study-specific assessments/procedures being conducted.
- Subject ≥ 18 years old at the time of signing the informed consent form (ICF)
- Confirmed histology of primary diffuse large B-cell lymphoma of the CNS (according to the 2022 WHO classification) or confirmed cytology of primary vitreoretinal diffuse large B-cell lymphoma, with CD20 positivity in immunohistochemical staining or flow cytometry at any point in the disease history.
- Subjects with relapsed or refractory (R/R) PCNSL or PVRL after at least one line of systemic therapy. Subject with R/R PCNSL must have previously received at least high dose methotrexate. Subject with R/R PVRL must have received either intravenous high dose methotrexate or intraocular methotrexate (PVRL cohort). Subjects can have received radiotherapy or intensive chemotherapy with hematopoietic stem cell rescue as part of treatment of the PCNSL or PVRL.
- ECOG performance status 0 to 2.
- Estimated minimum life expectancy of ≥ 2 months.
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- R/R PCNSL subjects with evaluable disease on brain MRI.
- Able to swallow capsules (stomach tube not allowed)
- Adequate hematopoietic function:
- Absolute neutrophil count of ≥ 1.0 G/L without G-CSF support for at least 7 days before screening
- Platelet count of ≥ 50 G/L without platelet transfusion within 7 days before screening
- Hemoglobin ≥ 8.0 g/dL without RBC transfusion within 7 days before screening
- Adequate renal function: calculated by Cockcroft-Gault equation creatinine clearance > 40 ml/min. Subjects with calculated creatinine clearance > 40 and < 60ml/min lenalidomide dose will be adjusted.
- Adequate liver function: Serum total bilirubin level ≤ 2.0 mg/dl [34 µmol/L] (unless bilirubin rise is due to Gilbert's syndrome) and serum transaminases (AST or ALT) ≤ 3 upper normal limits.
- Able to understand teratogenic risks of the treatment (Lenalidomide).
- Women of childbearing potential (WOCBP) should agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study treatment, 2) while participating in the study, 3) dose interruptions, and 4) for at least 12 months after the final dose of rituximab, or for at least 12 months after the final dose of epcoritamab, or for at least 28 days after the final dose of lenalidomide . WOCBP should also agree to abstain from breastfeeding during study participation and for at least 4 months after discontinuation of all study treatments.
- WOCBP should have a negative serum (beta-hCG) pregnancy test at screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle.
- Women should agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire study, until 12 months after the last administration of study treatment.
- Man who is sexually active with a female of reproductive potential and has not had a vasectomy should agree to use a highly effective / an acceptable method of birth control (ie, condom) and must agree not to donate sperm, until 28 days after the final dose of lenalidomide and/or until 12 months after the final dose of epcoritamab and rituximab.
- Subject covered by any social security system (France).
- Subject (or their legally acceptable representative/trusted person) who understands and speaks one of the country official languages unless local regulation authorizes independent translators.
Who cannot join
- Subject who meets any of the following criteria should be excluded from enrollment in the study:
- T-cell lymphoma.
- Cerebral localization of a systemic lymphoma.
- Prior history of organ transplantation or other cause of severe immunodeficiency.
- Known Human Immunodeficiency Virus (HIV) or Positive HTLV1 serology.
- Active Hepatitis B Virus (HBV) infection (DNA PCR-positive) or active hepatitis C Virus (HCV) infection (RNA PCR-positive). Subjects with evidence of prior HBV infection but who are PCR-negative are permitted in the study but should receive prophylactic antiviral therapy. Subjects who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable.
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- Persistent SARS-CoV-2 infection. Subjects who have had or currently have a SARS-CoV-2 infection must demonstrate symptom resolution and provide a negative nasopharyngeal PCR test at time of inclusion. Both of these requirements must be met for the subject to be considered clear of the virus.
- Impossibility to follow the calendar of exams because of geographic, social, or psychological reasons.
- Active malignancy other than the one treated in this Study. Prior history of malignancies (other than inclusion diagnosis) unless the subject has been free of the disease for ≥ 2 years. However, subjects with the following history/concurrent conditions are allowed:
- Non-invasive basal cell or epidermoid carcinoma
- In situ Carcinoma of the cervix
- In situ Carcinoma of the breast
- Non-invasive, superficial bladder cancer
- Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis [TNM] clinical staging system
- Any curable cancer with a complete response of >2 years duration
- Known or suspected hypersensitivity to the active substance or to any of the excipients.
- Any previous treatment with CAR-T therapy within 30 days prior to enrollment.
- Receiving immunosuppressive therapy, including more than the equivalent of 20 mg of prednisolone daily, unless for control of lymphoma or intermittent prophylaxis/treatment of allergic reactions.
- Any previous treatment with a bispecific antibody targeting CD3 and CD20 and/or with lenalidomide, regardless of the time and duration.
- Seizure disorder requiring anti-epileptic therapy unless related to lymphoma.
- Vaccination with live, attenuated vaccines within 28 days prior of enrollment (except severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Experimental and/or non-authorized SARS-CoV-2 vaccinations are not allowed.
- Use of any standard or experimental anti-cancer drug therapy within 28 days of the start (Day 1) of study treatment.
- Major surgery within 4 weeks prior to enrollment
- Clinically significant cardiovascular disease, including:
- Myocardial infarction within 1 year prior to enrollment, or unstable or uncontrol disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) cardiac arrhythmia (CTCAE Version 5.0 Grade 2 or higher), or clinically significant ECG abnormalities.
- Stroke within 6 months prior to enrollment.
- Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment at time of enrollment.
- Contraindication to all uric acid lowering agents.
- Clinically significant liver disease, including active hepatitis, current alcohol abuse, or cirrhosis.
- Active tuberculosis or history of treatment for active tuberculosis within the past 12 months.
- Receiving immunostimulatory agent.
- Prior allogeneic hematopoietic stem cell transplantation.
- Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision).
- Subject deprived of his/her liberty by a judicial or administrative decision.
- Subject hospitalized without consent.
- Adult subject under legal protection.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
France13 sites, 9 recruiting
- Recruiting
INSTITUT BERGONIE - Service d'Oncologie Médicale
Bordeaux
Dr. SCHMITT
- Recruiting
INSTITUT D'HEMATOLOGIE DE BASSE NORMANDIE - Service Hématologie
Caen
Dr. DAMAJ
- Recruiting
CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique
Clermont-Ferrand
Dr. MOLUCON-CHABROT
- Recruiting
CHU DE LILLE - HOPITAL CLAUDE HURIEZ - Service des Maladies du Sang
Lille
Pr. MORSCHHAUSER
- Active, not recruiting
CHR DE MARSEILLE - CHU TIMONE - Service de Neuro-Oncologie
Marseille
- Active, not recruiting
CHRU DE NANCY - HOPITAL CENTRAL - Service de Neurologie
Nancy
- Recruiting
GHU PITIE-SALPETRIERE - CHARLES FOIX - Service Neurologie
Paris
Dr. HOUILLIER
- Active, not recruiting
HOPITAL DE LA PITIE SALPETRIERE - Service Hématologie Clinique
Paris
- Recruiting
CHU LYON-SUD - Hématologie Clinique
Pierre-Bénite
Pr. Ghesquieres
- Active, not recruiting
CHU PONTCHAILLOU - Hématologie Clinique
Rennes
- Recruiting
INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie
Saint-Cloud
Dr. GILBERT
- Recruiting
IUCT ONCOPOLE - Service Hématologie
Toulouse
Dr. OBERIC
- Recruiting
CHU BRETONNEAU - Service Cancérologie - Hématologie et Thérapie Cellulaire
Tours
Pr. Emmanuel Gyan, emmanuel.gyan@univ-tours.fr
About this study
Official title: A Phase 2 Study Evaluating Epcoritamab in Subjects With Relapsed and Refractory Primary Diffuse Large B-cell Lymphoma of the CNS Treated With Lenalidomide and Rituximab
The purpose of this phase 2 study is to evaluate the efficacy and safety of epcoritamab in subjects with relapsed or refractory primary diffuse large B-cell lymphoma of the Central Nervous System treated with rituximab and lenalidomide.
Read the detailed description
Primary CNS DLBCL has an altered prognostic compared to systemic DLBCL mostly due to an increased relapse rate. PCNSL patients for whom the global prognostic remains poor, calling for improved treatment at relapse.
Considering the good results of R2 regimen in R/R PCNSL and the efficacy and favorable safety profile of epcoritamab in R/R systemic DLBCL, the addition of Epcoritamab to the combination of R2 might significantly improve the prognosis of PCNSL patients at relapse. In addition, it is expected that IMiDs could potentially increase the efficiency of epcoritamab by stimulating the immune system.
- Conditions
- Primary CNS Lymphoma (PCNSL)
- Being tested
- Epcoritamab
- Keywords
- primary CNS lymphoma, treatment for primary CNS lymphoma, epcoritamab treatment, rituximab and lenalidomide treatment, Primary CNS Lymphoma (PCNSL)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpcoritamabDrug
Epcoritamab Investigational Medicinal Product (IMP): Epcoritamab will be used during induction phase and Maintenance phase.
| Study group | Role | What they receive |
|---|---|---|
| experimental/epcoritamab | Experimental | Investigational Medicinal Product (IMP): Epcoritamab will be used during induction phase and Maintenance phase.
Auxiliary Medicinal Products (AMP): Rituximab and Lenalidomide
Standard use for AMP is:
Induction:
At cycle 1: Rituximab IV 375mg/m2 Day 1, 8, 15, 22; Lenalidomide 20mg oral route Day 1-Day 21 At cycle 2-3: Day 1: rituximab IV 375mg/m2; Lenalidomide 20mg oral route Day 1-Day 21 At cycle 4-8: Day 1: rituximab IV 375mg/m2; Lenalidomide 20mg oral route Day 1-Day 21
Maintenance:
At cycle 9-20: Day 1: Lenalidomide 20mg oral route Day 1-D21 (12 cycles corresponding to one year of maintenance treatment) Receives: Drug: Epcoritamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The best Objective Response rate (ORR) in the R/R PCNSL cohort
Objective Response rate
Measured: after 8 months or before in case of permanent treatment discontinuation
Secondary outcomes (16)
Objective response rate (CR + CRu + PR)
Objective response rate
Measured: after 8 months or before in case of permanent treatment discontinuation
Best objective response rate (CR + CRu + PR) in the PVRL cohort
Objective response rate
Measured: after 8 months or before in case of permanent treatment discontinuation
Objective response rate (CR + CRu + PR) in the PVRL cohort
Objective response rate
Measured: after 8 months or before in case of permanent treatment discontinuation
Best complete response rate (CR+CRu)
Best complete response rate
Measured: after 8 months or before in case of permanent treatment discontinuation
Time to objective response (TTR) according to IPCG recommendations
Time to objective response
Measured: 44 months after first patient in
Progression-free survival (PFS) according to IPCG recommendations
Progression-free survival
Measured: 56 months after first patient in
Duration of response (DOR) according to IPCG recommendations
Duration of response
Measured: 56 months after first patient in
Overall Survival (OS)
Overall Survival
Measured: 56 months after first patient in
Time to next treatment (TTNT)
Time to next treatment
Measured: 56 months after first patient in
Incidence and severity of AEs, special focus on ICANS, CRS and TLS
Incidence and severity
Measured: 56 months after first patient in
Incidence and severity of changes in laboratory values
Incidence and severity
Measured: 44 months after first patient in
Incidence of dose delay and treatment discontinuation
Incidence of dose delay
Measured: 44 months after first patient in
Time to deterioration in physical functioning - EORTC QLQ-C30
EORTC QLQ-C30 quality of life questionnaire. 30 questions using a scale of 4: from 1 (not at all) to 4 (very much). (lower score (worse): 120 and higher score (better): 30)
Measured: 44 months after First Patient In
Cognitive evaluation with MoCA test
10 questions / topics with different scores (between 1 and 6) and with a total score /30" (lower score (worse): 0 and higher score (better)
Measured: 56 months after first patient in
Time to deterioration in physical functioning - QLQ-HG29
QLQ-HG29 Questionnary of Life: 29 additional questions using a scale of 4: from 1 (not at all) to 4 (very much). (lower score (worse): 116 and higher score (better): 29)
Measured: 44 months after First Patient In
Cognitive evaluation with with BEARNI test
5 questions / topics with different scores (between 5 and 8) and with a total score /30" (lower score (worse): 0 and higher score (better): 30)
Measured: 56 months after first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2025
- Study start22 Sep 2025
- Primary completionJan 2028 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary CNS Lymphoma (PCNSL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This open-label, multicenter, single-arm phase II study is designed to assess the efficacy / safety of sub-cutaneous epcoritamab in subjects with relapsed or refractory diffuse large B-cell primary CNS Lymphoma (principal cohort: PCNSL) and relapsed or refractory primary vitreo-retinal lymphoma (exploratory cohort: PVRL) treated with oral lenalidomide and intravenous rituximab
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Lymphoma Academic Research Organisation
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Hervé Pr. Ghesquieres, MD, Principal investigator, HCL - Hôpital Lyon Sud - Service d'Hématologie - 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite - FranceGabriel Dr. Antherieu, MD, Principal investigator, HCL - Hôpital Lyon Sud - Service d'Hématologie - 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite - France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06931652
- Sponsor's protocol ID
- e-REVRI
- Acronym
- E-REVRI
- Status last verified
- Jun 2026
- First submitted
- 7 Apr 2025
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ghesquieres H, Chevrier M, Laadhari M, Chinot O, Choquet S, Molucon-Chabrot C, Beauchesne P, Gressin R, Morschhauser F, Schmitt A, Gyan E, Hoang-Xuan K, Nicolas-Virelizier E, Cassoux N, Touitou V, Le Garff-Tavernier M, Savignoni A, Turbiez I, Soumelis V, Houillier C, Soussain C. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)dagger. Ann Oncol. 2019 Apr 1;30(4):621-628. doi: 10.1093/annonc/mdz032.
PubMed 30698644Top FU, Usta T, Gucesan S. [Determining headache characteristics among Health Sciences Faculty students and evaluating the cultural beliefs affecting their treatment selection(s)]. Agri. 2010 Jan;22(1):13-20. Turkish.
PubMed 20209410Houillier C, Dureau S, Taillandier L, Houot R, Chinot O, Molucon-Chabrot C, Schmitt A, Gressin R, Choquet S, Damaj G, Peyrade F, Abraham J, Delwail V, Gyan E, Sanhes L, Cornillon J, Garidi R, Delmer A, Al Jijakli A, Morel P, Waultier A, Paillassa J, Chauchet A, Gastinne T, Laadhari M, Plissonnier AS, Feuvret L, Cassoux N, Touitou V, Ricard D, Hoang-Xuan K, Soussain C; LOC Network for CNS Lymphoma. Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study. J Clin Oncol. 2022 Nov 10;40(32):3692-3698. doi: 10.1200/JCO.22.00491. Epub 2022 Jul 14.
PubMed 35834762O'Neill BP, Decker PA, Tieu C, Cerhan JR. The changing incidence of primary central nervous system lymphoma is driven primarily by the changing incidence in young and middle-aged men and differs from time trends in systemic diffuse large B-cell non-Hodgkin's lymphoma. Am J Hematol. 2013 Dec;88(12):997-1000. doi: 10.1002/ajh.23551. Epub 2013 Sep 12.
PubMed 23873804Bauchet L, Rigau V, Mathieu-Daude H, Figarella-Branger D, Hugues D, Palusseau L, Bauchet F, Fabbro M, Campello C, Capelle L, Durand A, Tretarre B, Frappaz D, Henin D, Menei P, Honnorat J, Segnarbieux F. French brain tumor data bank: methodology and first results on 10,000 cases. J Neurooncol. 2007 Sep;84(2):189-99. doi: 10.1007/s11060-007-9356-9. Epub 2007 Apr 13.
PubMed 17431547