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

Phase 2
Recruiting
Conditions
Relapsed/Refractory Large B-cell Lymphoma
Interventions
Drug: Epcoritamab, lenalidomide and rituximab
Registration Number
NCT06414148
Lead Sponsor
Peter MacCallum Cancer Centre, Australia
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.

Detailed Description

Patients who have received CAR T-cell therapy for Relapsed/Refractory Large B-Cell Lymphoma, are in Complete Metabolic Response (CMR) or Partial Metabolic Response (PMR) and MRD positive post CAR T-cell infusion are potentially eligible. Once these patients have provided their consent, they will enter the screening phase. All events of Cytokine Release Syndrome (CRS), Haemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS), Immune-Effector Cell Associated Neurologic Syndrome (ICANS), or infection must have completely resolved. Additionally, patients must have adequate organ and haematological function, and an ECOG performance status of up to 2.

Patients deemed eligible for the study will be randomised to receive Epcor-only (Arm A) or Epcor-R2 (Arm B) for 6 cycles. The primary endpoint is CMR by Lugano 2014 criteria at month 12 post CAR T-cell infusion.

Patients will undergo an interim response assessment after 2 cycles of treatment. Patients that complete the full 6 cycles of treatment or that discontinue treatment for any reason will have an End of Treatment visit and a Safety Follow-up visit at 60 days after Day 1 of Cycle 6. Patients with non-Progressive Disease (PD) then enter the follow-up phase of the study where they will undergo response assessments at month 12, 15, 18 and 24 after CAR T-cell infusion. Patients with PD at any time will complete a Progression visit. Patients that have completed the month 24 Follow-up visit or that they have progressed will be followed for survival and new anti-lymphoma therapy only. All patients will be followed for 2 years after the last patient randomised received the CAR T-cell infusion.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
40
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm AEpcoritamabEPCORITAMAB (EPCOR-ONLY)
Arm BEpcoritamab, lenalidomide and rituximabEPCORITAMAB, LENALIDOMIDE AND RITUXIMAB (EPCOR-R2)
Primary Outcome Measures
NameTimeMethod
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 infusionFrom start of treatment till the end of study, assessed up to approximately 12 months
Secondary Outcome Measures
NameTimeMethod
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 v5.0From 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) analysesFrom 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 therapyFrom start of treatment till the end of study, assessed up to approximately 6 months
The efficacy as assessed by molecular and conventional response criteria at defined time points with Overall Survival (OS) analysesFrom start of treatment till the end of study, assessed up to approximately 48 months
The deliverability as assessed by protocol-defined number of dose-reductions of lenalidomideFrom start of treatment till the end of study, assessed up to approximately 6 months

Trial Locations

Locations (6)

Fiona Stanley Hospital

🇦🇺

Murdoch, Western Australia, Australia

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

Royal Brisbane and Women's Hospital

🇦🇺

Herston, Queensland, Australia

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

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