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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06414148




Registration number
NCT06414148
Ethics application status
Date submitted
29/04/2024
Date registered
16/05/2024
Date last updated
16/05/2024

Titles & IDs
Public title
MRD-Directed Consolidation With Epcor-only or Epcor-R2 Post Anti-CD19 CAR TCell Therapy for Large B-Cell Lymphoma
Scientific title
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)
Secondary ID [1] 0 0
22/012
Universal Trial Number (UTN)
Trial acronym
EpLCART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Large B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Epcoritamab
Treatment: Drugs - Epcoritamab, lenalidomide and rituximab

Experimental: Arm A - EPCORITAMAB (EPCOR-ONLY)

Experimental: Arm B - EPCORITAMAB, LENALIDOMIDE AND RITUXIMAB (EPCOR-R2)


Treatment: Drugs: Epcoritamab
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: Drugs: Epcoritamab, lenalidomide and rituximab
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
From start of treatment till the end of study, assessed up to approximately 12 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
From start of treatment till the end of study, assessed up to approximately 48 months
Secondary outcome [2] 0 0
The efficacy as assessed by molecular and conventional response criteria at defined time points with Event Free Survival (EFS) analyses
Timepoint [2] 0 0
From start of treatment till the end of study, assessed up to approximately 48 months
Secondary outcome [3] 0 0
The efficacy as assessed by molecular and conventional response criteria at defined time points with Overall Survival (OS) analyses
Timepoint [3] 0 0
From start of treatment till the end of study, assessed up to approximately 48 months
Secondary outcome [4] 0 0
The deliverability as assessed by rates of completion of the course of therapy
Timepoint [4] 0 0
From start of treatment till the end of study, assessed up to approximately 6 months
Secondary outcome [5] 0 0
The deliverability as assessed by protocol-defined number of dose-reductions of lenalidomide
Timepoint [5] 0 0
From start of treatment till the end of study, assessed up to approximately 6 months

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Age = 18 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 a PET/CT performed

6. MRD positive by a ctDNA assay on a blood sample 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
7/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2028
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [6] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AbbVie
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06414148
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Dickinson, MBBS, D Med Sc, FRACP, FRCPA
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06414148