MRD-Directed Consolidation With Epcor-only or Epcor-R2 Post Anti-CD19 CAR TCell Therapy for Large B-Cell Lymphoma

NCT06414148 | Recruiting Phase 2 DMC

• 1 other identifier: 22/012
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase II open-label, two-arm randomised non-comparative, multi-centre study to evaluate the efficacy of Epcor-only (Epcoritamab alone) or Epcor-R2 (Epcoritamab, lenalidomide and rituximab) as consolidation post anti-CD19 CAR T-cell therapy for patients that have responded by conventional criteria but who are at high risk of progression by virtue of being Minimal Residual Disease (MRD) positive as determined by a Circulating Tumour DNA (ctDNA) assay.

Conditions

Relapsed/Refractory Large B-cell Lymphoma

Keywords

Minimal Residual Disease; Large B-Cell Lymphoma; Anti-CD19; CAR T; ctDNA; Lymphoma; DLBCL; HGBL; Epcoritamab; Lenalidomide; Rituximab

Outcome Measures

Primary Outcomes (1)

• The efficacy of Epcor-only (epcoritamab alone) or Epcor-R2 (epcoritamab, lenalidomide and rituximab) consolidation as assessed by conventional (Lugano 2014) response criteria at month 12 after the CART infusion

  From start of treatment till the end of study, assessed up to approximately 12 months

Secondary Outcomes (5)

• To evaluate the safety of time-limited Epcor-only or Epcor-R2 consolidation post CAR T-cell therapy according to number of participants with treatment-related adverse events (AE) as assessed by CTCAE v5.0

  From start of treatment till the end of study, assessed up to approximately 48 months

• The efficacy as assessed by molecular and conventional response criteria at defined time points with Event Free Survival (EFS) analyses

  From start of treatment till the end of study, assessed up to approximately 48 months

• The efficacy as assessed by molecular and conventional response criteria at defined time points with Overall Survival (OS) analyses

  From start of treatment till the end of study, assessed up to approximately 48 months

• The deliverability as assessed by rates of completion of the course of therapy

  From start of treatment till the end of study, assessed up to approximately 6 months

• The deliverability as assessed by protocol-defined number of dose-reductions of lenalidomide

  From start of treatment till the end of study, assessed up to approximately 6 months

Other Outcomes (2)

• Correlation between tumour/immunological associations (using cytokine/chemokine profiles, clonal kinetics and phenotypic changes) and response (EFS and OS)

  From start of treatment till the end of study, assessed up to approximately 48 months

• Correlation between tumour/immunological associations (using cytokine/chemokine profiles, clonal kinetics and phenotypic changes) and treatment toxicity (number of participants with treatment-related AE)

  From start of treatment till the end of study, assessed up to approximately 48 months

Study Arms (2)

Arm A

EXPERIMENTAL

EPCORITAMAB (EPCOR-ONLY)

Drug: Epcoritamab

Arm B

EXPERIMENTAL

EPCORITAMAB, LENALIDOMIDE AND RITUXIMAB (EPCOR-R2)

Drug: Epcoritamab, lenalidomide and rituximab

Interventions

Epcoritamab DRUG

Epcoritamab will be administered as a 28-day cycle. In Cycle 1 and 2, epcoritamab will be given with step up dosing in Cycle 1. From Cycle 3 onwards dosing will be on Day 1 and 15 of each cycle.

Arm A

Epcoritamab, lenalidomide and rituximab DRUG

Treatment with epcoritamab will be administered following the same dosing schedule as Arm A. On days where rituximab and/or lenalidomide are also due, epcoritamab should be administered last. Patients will receive lenalidomide once daily on Day 1-21 of each 28-day cycle, starting at Cycle 1 through to Cycle 6. Patients will receive rituximab administered by intravenous (IV) infusion on Day 1, 8, 15 and 22 of Cycle 1 and on Day 1 only of Cycles 2-6.

Arm B

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 16 years old at the time of signing the patient information and consent form (PICF)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• A diagnosis of relapsed/refractory large B-cell lymphoma
• Received Therapeutic Good Administration (TGA) approved anti-CD19 CAR T-cell therapy as the most recent large B-cell lymphoma treatment.
• Partial metabolic response (PMR) or complete metabolic response (CMR) as per the Lugano criteria on the most recent PET/CT performed at any point between Day +25 and Day +100 post CAR T-cell infusion, when compared with the most recent PET/CT prior to CAR T-cell infusion.
• MRD positive by a ctDNA assay on a blood sample taken at any point between Day +25 and Day +100 post CAR T-cell infusion.
• Adequate haematological function documented within 7 days prior to randomisation
• Adequate cardiac function.
• Adequate renal function, documented within 7 days prior to randomisation
• Adequate hepatic function documented within 7 days prior to randomisation
• Complete resolution of cytokine release syndrome (CRS), macrophage-activation syndrome (MAS)/haemophagocytic lymphohistiocytosis (HLH) or immune effector cell-associated neurotoxicity syndrome (ICANS) related to prior CAR T-cell therapy.
• Female patients of childbearing potential (FCBP) must be willing to follow the contraceptive method/procedure as outline in the PICF
• Sexually active males must agree to use a condom during sexual contact with a pregnant female or a FCBP for the course of the study through to 4 months after the last dose of epcoritamab, even if he has undergone a successful vasectomy
• Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction. Men must also not donate sperm during the trial and for 4 months after receiving the last dose of epcoritamab
• The patient understands the purpose of the trial and procedures required for the trial which includes compliance with the protocol requirements and restrictions listed in the PICF and in this protocol

You may not qualify if:

• A history of Grade 4 CRS or ICANS related to prior CAR T-cell therapy
• Patients whose lymphoma is known to be CD20 negative on the most recent biopsy prior to CAR T-cell therapy
• Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment
• Progression or relapse within 3 months after a regimen containing a bispecific antibody targeting CD3 and CD20
• A diagnosis of primary central nervous system (CNS) lymphoma
• Active secondary CNS involvement of lymphoma at time of screening
• A known history or current autoimmune disease or other diseases resulting in permanent immunosuppression
• Known cognitive impairment would place the patient at increased risk of complications from ICANS
• A known history of hepatitis B serology consistent with acute or chronic infection
• A known history of hepatitis C serology consistent with acute or chronic infection
• A known history of testing positive for human immunodeficiency virus (HIV)
• Any comorbidity conferring a life expectancy of \< 5 years (e.g., second malignancy) or that in the opinion of the site investigator may significantly impact the ability to complete the trial therapy and follow-up or affect the interpretation of results
• Exposed to live or live attenuated vaccine within 4 weeks prior to signing the PICF.
• Women who are pregnant or lactating
• Known hypersensitivity to epcoritamab, lenalidomide, rituximab, tocilizumab or their excipients

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• AbbVie: collaborator

Study Sites (6)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

NOT YET RECRUITING

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

NOT YET RECRUITING

Alfred Hospital

Melbourne, Victoria, 3000, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Recurrence; Neoplasm, Residual; Lymphoma

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael Dickinson, MBBS, D Med Sc, FRACP, FRCPA

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: A phase II open-label, two-arm randomised non-comparative, multicentre study

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 16, 2024
• Study Start: May 14, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6)