Primary CNS Lymphoma Clinical Trial
— CAROUSELOfficial title:
Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary Central Nervous System (CNS) Lymphoma
Verified date | May 2024 |
Source | University College, London |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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 Primary CNS Lymphoma. The study will evaluate the feasibility of generating the ATIMP, the safety of administering CD19CAR T-cell therapy and how effectively CD19CAR T-cells engraft, expand and persist following administration in patients with relapsed/refractory primary CNS lymphoma.
Status | Active, not recruiting |
Enrollment | 12 |
Est. completion date | December 2032 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 16 Years and older |
Eligibility | Inclusion Criteria: 1. Age =16 2. Patients with a histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) confined to the CNS (Primary CNS Lymphoma (PCNSL)) 3. 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. 4. Measurable disease on contrast-enhanced MRI 5. Unsuitable for alternative salvage therapies as determined by their treating physician 6. Agreement to have a pregnancy test, use highly effective contraception (if applicable) 7. 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): 1. CD19 negative disease 2. Evidence of secondary CNS lymphoma 3. Prior allogeneic haematopoietic stem cell transplant 4. Active hepatitis B, C or HIV infection 5. Oxygen saturation =90% on air 6. Bilirubin >2 x upper limit of normal 7. Glomerular Filtration Rate (GFR) <50ml/min 8. Women who are pregnant or breast feeding 9. Inability to tolerate leucapheresis 10. ECOG 3-4 11. Known allergy to albumin or Dimethyl sulfoxide (DMSO) 12. Life expectancy <3months 13. Arrhythmias or significant cardiac disease and left ventricular ejection fraction <40% 14. Pre-existing neurological disorders (other than CNS involvement of underlying haematological malignancy) 15. Any contraindications to PD-1 antibody Pembrolizumab 16. 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 17. 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): 1. Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion 2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion 3. Theme 2 only: 1. presence of grade 3 or 4 ICANS casually related to the ATIMP following infusion of Dose 1 2. 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 3. grade 3-4 CRS following infusion of Dose 1 4. 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 5. pregnancy |
Country | Name | City | State |
---|---|---|---|
United Kingdom | University College London Hospital | London |
Lead Sponsor | Collaborator |
---|---|
University College, London |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP | Toxicity following CD19CAR T-cell administration as evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP | 28 days | |
Primary | Feasibility of manufacturing CD19CAR T-cells evaluated by the number of therapeutic products generated | Feasibility of adequate leucapheresis collection and generation of CD19CAR T-cells as evaluated by the number of therapeutic products generated. | 28 days | |
Secondary | Response at 1 and 3 months | Proportion of patients achieving a Complete Response (CR) or Partial Response (PR) at 1 and 3 months post CD19CAR T-cells infusion: Theme 1 (i.v.) and Theme 2 (intraventricular) | From CD19CAR T-cells infusion to 1 and 3 months | |
Secondary | Frequency of circulating CD19CAR T-cells in peripheral blood | Frequency of circulating CD19CAR T-cells in peripheral blood as assessed by flow cytometry and qPCR | From CD19CAR T-cells infusion up to 2 years post CD19CAR T-cells infusion | |
Secondary | Incidence of B-cell aplasia | Incidence of B-cell aplasia | From CD19CAR T-cells infusion up to 2 years post CD19CAR T-cells infusion | |
Secondary | Relapse rate at 1 and 2 years | Proportion of patients who have relapsed at 1 and 2 years after CD19CAR T-cells infusion | At 1 year and 2 years after CD19CAR T-cells infusion | |
Secondary | Progression Free Survival (PFS) at 1 and 2 years | Progression Free Survival at 1 and 2 years after CD19CAR T-cells infusion | At 1 year and 2 years after CD19CAR T-cells infusion | |
Secondary | Overall Survival (OS) at 1 and 2 years | Overall Survival at 1 and 2 years after immunotherapy with CD19CAR T-cells infusion | At 1 year and 2 years after CD19CAR T-cells infusion |
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