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

Primary CNS Lymphoma Clinical Trial

Official title: Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary Central Nervous System (CNS) Lymphoma

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial 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 Primary CNS Lymphoma. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with CD19CAR vector to generate CD19CAR T-cells.

Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. Patients will receive pre-conditioning lymphodepleting (LD) chemotherapy with cyclophosphamide 60mg/kg on Day -6, fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3) and pembrolizumab 200mg on Day -1.

All patients will be treated on Theme 1 of the study with 250 x 10^6 CD19 CAR T-cells i.v. following LD chemotherapy as described above. Patients with response of Stable Disease (SD) or Progressive Disease (PD) at Day 28 (or frank relapse beyond Day 28) and in the absence of severe toxicity related to the ATIMP, will be potentially eligible for Theme 2 of the study where they can receive Dose 2, a single dose of 25 x 10^6 CD19CAR T-cells intraventricularly via an Ommaya reservoir following LD chemotherapy as described above.

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.

Following infusion of CD19CAR T-cell therapy patients will be monitored for between 2-4 weeks as an inpatient. Following discharge, patients will enter the interventional follow up phase and be followed up for 2 years. Patients will be seen monthly for the first 6 months, then 6 weekly to 12 months and then 3 monthly until 2 years post CD19CAR T-cell infusion.

If patients relapse within the first 2 years post CD19CAR T-cell infusion they will come off the interventional follow up and will be followed up annually until the end of trial is declared.

After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until the end of trial is declared. ;

Related Conditions & MeSH terms

• Lymphoma
• Primary CNS Lymphoma

• NCT number: NCT04443829
• Study type: Interventional
• Source: University College, London
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 23, 2021
• Completion date: December 2032