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

PHASE2RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Age ≥ 16 years old at the time of signing the patient information and consent form (PICF)
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  3. A diagnosis of relapsed/refractory large B-cell lymphoma
  4. Received Therapeutic Good Administration (TGA) approved anti-CD19 CAR T-cell therapy as the most recent large B-cell lymphoma treatment.
  5. 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.
  6. 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.
  7. Adequate haematological function documented within 7 days prior to randomisation
  8. Adequate cardiac function.
  9. Adequate renal function, documented within 7 days prior to randomisation
  10. Adequate hepatic function documented within 7 days prior to randomisation
  11. 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.
  12. Female patients of childbearing potential (FCBP) must be willing to follow the contraceptive method/procedure as outline in the PICF
  13. 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
  14. 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
  15. 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

  1. A history of Grade 4 CRS or ICANS related to prior CAR T-cell therapy
  2. Patients whose lymphoma is known to be CD20 negative on the most recent biopsy prior to CAR T-cell therapy
  3. Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment
  4. Progression or relapse within 3 months after a regimen containing a bispecific antibody targeting CD3 and CD20
  5. A diagnosis of primary central nervous system (CNS) lymphoma
  6. Active secondary CNS involvement of lymphoma at time of screening
  7. A known history or current autoimmune disease or other diseases resulting in permanent immunosuppression
  8. Known cognitive impairment would place the patient at increased risk of complications from ICANS
  9. A known history of hepatitis B serology consistent with acute or chronic infection
  10. A known history of hepatitis C serology consistent with acute or chronic infection
  11. A known history of testing positive for human immunodeficiency virus (HIV)
  12. 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
  13. Exposed to live or live attenuated vaccine within 4 weeks prior to signing the PICF.
  14. Women who are pregnant or lactating
  15. Known hypersensitivity to epcoritamab, lenalidomide, rituximab, tocilizumab or their excipients
  16. Presence of any psychological, social or geographical or other condition for which participation would not be in the best interest of the patient

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT06414148

Intervention or treatment

DRUG: Epcoritamab

DRUG: Epcoritamab, lenalidomide and rituximab

Conditions

  • Relapsed/Refractory Large B-cell Lymphoma

  • Condition: Relapsed/Refractory Large B-cell Lymphoma

  • DRUG: Epcoritamab and other drugs

  • Camperdown, New South Wales, Australia and more

  • Sponsor: Peter MacCallum Cancer Centre, Australia

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Royal Prince Alfred Hospital

Select from list below to view details:

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, Australia

  • Westmead Hospital

    Westmead, New South Wales, Australia

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, Australia

  • Alfred Hospital

    Melbourne, Victoria, Australia

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Who is running the clinical trial?

PMCCA

Peter MacCallum Cancer Centre, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Arm A
  • EPCORITAMAB (EPCOR-ONLY)
Drug: Epcoritamab
    EXPERIMENTAL: Arm B
    • EPCORITAMAB, LENALIDOMIDE AND RITUXIMAB (EPCOR-R2)
    Drug: Epcoritamab, lenalidomide and rituximab

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime 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 infusionNot SpecifiedFrom start of treatment till the end of study, assessed up to approximately 12 months

      Secondary Outcome

      MeasureDescriptionTime 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 v5.0Not SpecifiedFrom 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) analysesNot SpecifiedFrom 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) analysesNot SpecifiedFrom 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 therapyNot SpecifiedFrom 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 lenalidomideNot SpecifiedFrom start of treatment till the end of study, assessed up to approximately 6 months
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

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

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