Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary CNS Lymphoma

NCT04443829 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: UCL/126892
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Primary CNS Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Response at 1 and 3 months

  From CD19CAR T-cells infusion to 1 and 3 months

• Frequency of circulating CD19CAR T-cells in peripheral blood

  From CD19CAR T-cells infusion up to 2 years post CD19CAR T-cells infusion

• Incidence of B-cell aplasia

  From CD19CAR T-cells infusion up to 2 years post CD19CAR T-cells infusion

• Relapse rate at 1 and 2 years

  At 1 year and 2 years after CD19CAR T-cells infusion

• Progression Free Survival (PFS) at 1 and 2 years

  At 1 year and 2 years after CD19CAR T-cells infusion

Study Arms (1)

CD19CAR T-cells

EXPERIMENTAL

Treatment with the ATIMP: CD19CAR T-cells

Biological: CD19CAR T-cells

Interventions

CD19CAR T-cells BIOLOGICAL

Infusion with: CD19CAR T-cells

CD19CAR T-cells

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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'.

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

University College London Hospital

London, WC1E6BT, United Kingdom

Location

Study Officials

• Claire Roddie

  University College London Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 23, 2020
• Study Start: March 23, 2021
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2032
• Last Updated: May 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)