Trial Title:
MRD-Directed Consolidation With Epcor-only or Epcor-R2 Post Anti-CD19 CAR TCell Therapy for Large B-Cell Lymphoma
NCT ID:
NCT06414148
Condition:
Relapsed/Refractory Large B-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Rituximab
Lenalidomide
Conditions: Keywords:
Minimal Residual Disease
Large B-Cell Lymphoma
Anti-CD19
CAR T
ctDNA
Lymphoma
DLBCL
HGBL
Epcoritamab
Lenalidomide
Rituximab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
A phase II open-label, two-arm randomised non-comparative, multicentre study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Epcoritamab
Description:
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.
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Epcoritamab, lenalidomide and rituximab
Description:
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.
Arm group label:
Arm B
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.
Criteria for eligibility:
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
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Royal Prince Alfred Hospital
Address:
City:
Camperdown
Zip:
2050
Country:
Australia
Status:
Not yet recruiting
Facility:
Name:
Westmead Hospital
Address:
City:
Westmead
Zip:
2145
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Emily Blyth
Phone:
+61288905555
Email:
emily.blyth@sydney.edu.au
Facility:
Name:
Royal Brisbane and Women's Hospital
Address:
City:
Herston
Zip:
4029
Country:
Australia
Status:
Not yet recruiting
Facility:
Name:
Alfred Hospital
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Shafqat Inam
Phone:
+61390766000
Email:
S.Inam@alfred.org.au
Facility:
Name:
Peter MacCallum Cancer Centre
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Michael Dickinson
Phone:
+61385995000
Email:
michael.dickinson@petermac.org
Facility:
Name:
Fiona Stanley Hospital
Address:
City:
Murdoch
Zip:
6150
Country:
Australia
Status:
Not yet recruiting
Start date:
May 14, 2024
Completion date:
May 2028
Lead sponsor:
Agency:
Peter MacCallum Cancer Centre, Australia
Agency class:
Other
Collaborator:
Agency:
AbbVie
Agency class:
Industry
Source:
Peter MacCallum Cancer Centre, Australia
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06414148
