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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
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.
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.
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
NOT_YET_RECRUITINGWestmead Hospital
Westmead, New South Wales, Australia
RECRUITINGRoyal Brisbane and Women's Hospital
Herston, Queensland, Australia
NOT_YET_RECRUITINGAlfred Hospital
Melbourne, Victoria, Australia
RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGFiona Stanley Hospital
Murdoch, Western Australia, Australia
NOT_YET_RECRUITINGThe 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
Time frame: From start of treatment till the end of study, assessed up to approximately 12 months
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From start of treatment till the end of study, assessed up to approximately 6 months
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