Status:
ACTIVE_NOT_RECRUITING
Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary CNS Lymphoma
Lead Sponsor:
University College, London
Conditions:
Primary CNS Lymphoma
Eligibility:
All Genders
16+ years
Phase:
PHASE1
Brief Summary
The CAROUSEL Trial is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with relapsed/refractory P...
Detailed Description
The CAROUSEL Trial is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with relapsed/refractory P...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Age ≥16
- Patients with a histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) confined to the CNS (Primary CNS Lymphoma (PCNSL))
- Relapsed\* or refractory CD19+ PCNSL, defined as disease progression following CR/CRu/PR, or failure to achieve PR, after one or more lines of a high-dose methotrexate-containing protocol \*Histological confirmation by re-biopsy at relapse is recommended if feasible. However, patients will be eligible without re-biopsy provided the initial diagnostic material is available and current MRI imaging features are consistent with PCNSL by neuroradiology review.
- Measurable disease on contrast-enhanced MRI
- Unsuitable for alternative salvage therapies as determined by their treating physician
- Agreement to have a pregnancy test, use highly effective contraception (if applicable)
- Written informed consent\*\* \*\* Some patients with PCNSL may be incapable of providing their own consent due to the neurological effects of their disease. In these cases a legal representative may be sought to provide consent'.
- Exclusion Criteria (Registration):
- CD19 negative disease
- Evidence of secondary CNS lymphoma
- Prior allogeneic haematopoietic stem cell transplant
- Active hepatitis B, C or HIV infection
- Oxygen saturation ≤90% on air
- Bilirubin \>2 x upper limit of normal
- Glomerular Filtration Rate (GFR) \<50ml/min
- Women who are pregnant or breast feeding
- Inability to tolerate leucapheresis
- ECOG 3-4
- Known allergy to albumin or Dimethyl sulfoxide (DMSO)
- Life expectancy \<3months
- Arrhythmias or significant cardiac disease and left ventricular ejection fraction \<40%
- Pre-existing neurological disorders (other than CNS involvement of underlying haematological malignancy)
- Any contraindications to PD-1 antibody Pembrolizumab
- History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months
- Evidence of active pneumonitis on chest computed tomography (CT) or positron emission tomography (PET)-CT scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia (e.g. bronchiolitis obliterans), or idiopathic pneumonitis. Prior radiation pneumonitis in the radiation field (fibrosis) is allowed (if \>24 weeks since the event)
- Exclusion criteria: for CD19CAR T-cell infusion ( Dose 1/i.v. and Dose 2/intraventricular):
- Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion
- Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion
- Theme 2 only:
- presence of grade 3 or 4 ICANS casually related to the ATIMP following infusion of Dose 1
- grade 1-2 neurotoxicity (if occurred) following Theme 1 dosing (Dose 1/i.v CD19CAR Tcell dose) that has not fully resolved prior to proposed administration of 2nd CD19CAR T-cell infusion (Dose /intraventricular) for theme 2
- grade 3-4 CRS following infusion of Dose 1
- persisting grade 2 CRS following Theme 1 dosing (Dose 1/i.v CD19CAR T-cell dose) that has not resolved to ≤ grade 1 CRS prior to proposed administration of 2nd CD19CAR Tcell infusion (Dose 2/intraventricular) for theme 2
- pregnancy
Exclusion
Key Trial Info
Start Date :
March 23 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2032
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT04443829
Start Date
March 23 2021
End Date
December 1 2032
Last Update
May 30 2024
Active Locations (1)
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1
University College London Hospital
London, United Kingdom, WC1E6BT