Study of Epcoritamab in R/R Primary Diffuse Large B-cell Lymphoma of the CNS Treated With Lenalidomide and Rituximab

NCT06931652 | Recruiting Phase 2 DMC

• 1 other identifier: e-REVRI
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Primary CNS Lymphoma (PCNSL)

Keywords

primary CNS lymphoma; treatment for primary CNS lymphoma; epcoritamab treatment; rituximab and lenalidomide treatment; Primary CNS Lymphoma (PCNSL)

Outcome Measures

Primary Outcomes (1)

• The best Objective Response rate (ORR) in the R/R PCNSL cohort

  Objective Response rate

  after 8 months or before in case of permanent treatment discontinuation

Secondary Outcomes (16)

• Objective response rate (CR + CRu + PR)

  after 8 months or before in case of permanent treatment discontinuation

• Best objective response rate (CR + CRu + PR) in the PVRL cohort

  after 8 months or before in case of permanent treatment discontinuation

• Objective response rate (CR + CRu + PR) in the PVRL cohort

  after 8 months or before in case of permanent treatment discontinuation

• Best complete response rate (CR+CRu)

  after 8 months or before in case of permanent treatment discontinuation

• Time to objective response (TTR) according to IPCG recommendations

  44 months after first patient in

Study Arms (1)

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)

Drug: Epcoritamab

Interventions

Epcoritamab DRUG

Epcoritamab Investigational Medicinal Product (IMP): Epcoritamab will be used during induction phase and Maintenance phase.

experimental/epcoritamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• Impossibility to follow the calendar of exams because of geographic, social, or psychological reasons.
• 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.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• AbbVie: collaborator

Study Sites (13)

INSTITUT BERGONIE - Service d'Oncologie Médicale

Bordeaux, France

ACTIVE NOT RECRUITING

INSTITUT D'HEMATOLOGIE DE BASSE NORMANDIE - Service Hématologie

Caen, France

RECRUITING

CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique

Clermont-Ferrand, France

RECRUITING

CHU DE LILLE - HOPITAL CLAUDE HURIEZ - Service des Maladies du Sang

Lille, France

RECRUITING

CHR DE MARSEILLE - CHU TIMONE - Service de Neuro-Oncologie

Marseille, France

ACTIVE NOT RECRUITING

CHRU DE NANCY - HOPITAL CENTRAL - Service de Neurologie

Nancy, France

ACTIVE NOT RECRUITING

GHU PITIE-SALPETRIERE - CHARLES FOIX - Service Neurologie

Paris, France

ACTIVE NOT RECRUITING

HOPITAL DE LA PITIE SALPETRIERE - Service Hématologie Clinique

Paris, France

ACTIVE NOT RECRUITING

CHU LYON-SUD - Hématologie Clinique

Pierre-Bénite, France

RECRUITING

CHU PONTCHAILLOU - Hématologie Clinique

Rennes, France

NOT YET RECRUITING

INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie

Saint-Cloud, France

ACTIVE NOT RECRUITING

IUCT ONCOPOLE - Service Hématologie

Toulouse, France

RECRUITING

CHU BRETONNEAU - Service Cancérologie - Hématologie et Thérapie Cellulaire

Tours, France

ACTIVE NOT RECRUITING

Related Publications (5)

• 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.

  PMID: 30698644 RESULT

• Top 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.

  PMID: 20209410 RESULT

• Houillier 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.

  PMID: 35834762 RESULT

• O'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.

  PMID: 23873804 RESULT

• Bauchet 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.

  PMID: 17431547 RESULT

Study Officials

• Hervé Pr. Ghesquieres, MD

  HCL - Hôpital Lyon Sud - Service d'Hématologie - 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite - France

  PRINCIPAL INVESTIGATOR

• Gabriel Dr. Antherieu, MD

  HCL - Hôpital Lyon Sud - Service d'Hématologie - 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite - France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Management

CONTACT

04 72 66 93 33; e-revri@lysarc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 17, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)