- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06414148
MRD-Directed Consolidation With Epcor-only or Epcor-R2 Post Anti-CD19 CAR TCell Therapy for Large B-Cell Lymphoma (EpLCART)
A Phase II Open-Label, Multi-Centre Study of Minimal Residual Disease-Directed Consolidation With Epcoritamab or Epcoritamab-Lenalidomide-Rituximab Post Anti-CD19 CAR TCell Therapy for Large B-Cell Lymphoma (EpLCART)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Royal Prince Alfred Hospital
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Westmead, New South Wales, Australia, 2145
- Westmead Hospital
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Queensland
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Herston, Queensland, Australia, 4029
- Royal Brisbane and Women's Hospital
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Victoria
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Melbourne, Victoria, Australia, 3000
- Peter MacCallum Cancer Centre
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Melbourne, Victoria, Australia, 3000
- Alfred Hospital
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Western Australia
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Murdoch, Western Australia, Australia, 6150
- Fiona Stanley Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria
- Age ≥ 18 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 a PET/CT performed
- MRD positive by a ctDNA assay on a blood sample 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
Exclusion Criteria
- 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
- Presence of any psychological, social or geographical or other condition for which participation would not be in the best interest of the patient
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A
EPCORITAMAB (EPCOR-ONLY)
|
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.
|
Experimental: Arm B
EPCORITAMAB, LENALIDOMIDE AND RITUXIMAB (EPCOR-R2)
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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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: From start of treatment till the end of study, assessed up to approximately 12 months
|
From start of treatment till the end of study, assessed up to approximately 12 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
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
|
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
|
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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From start of treatment till the end of study, assessed up to approximately 6 months
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Correlation between tumour/immunological associations (using cytokine/chemokine profiles, clonal kinetics and phenotypic changes) and response (EFS and OS)
Time Frame: From start of treatment till the end of study, assessed up to approximately 48 months
|
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)
Time Frame: From start of treatment till the end of study, assessed up to approximately 48 months
|
From start of treatment till the end of study, assessed up to approximately 48 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Michael Dickinson, MBBS, D Med Sc, FRACP, FRCPA, Peter MacCallum Cancer Centre, Australia
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Lenalidomide
- Rituximab
Other Study ID Numbers
- 22/012
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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