KCAT19

• Research type

  Research Study

• Full title

  Allogeneic T cells expressing T cell receptor-KDEL and the chimeric antigen receptor CAT19 for the treatment of advanced CD19+ malignancies

• IRAS ID

  1004920

• Contact name

  Karl Peggs

• Contact email

  k.peggs@ucl.c.uk

• Sponsor organisation

  University College London

• Eudract number

  2021-002878-88

• Clinicaltrials.gov Identifier

  NCT05391490

• Research summary

  The KCAT19 study will use cord-blood derived allogeneic (donor) T cells, modified to target B cell cancer cells and so they do not attack the normal cells of the patient (graft versus host disease, GvHD): these modified T cells will be referred to as KCAT19 T cells. Upon patient registration, the best available cord blood units will be selected for KCAT19 T cell manufacture based on how suitable they are to each patient (HLA matching). This approach has been adopted to address the rapid T-cell rejection as may be seen in a completely mismatched setting.
  Prior to KCAT19 T cell administration, patients will first receive pre-conditioning lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide to reduce the patient’s blood counts which will help the KCAT19 T cells engraft and persist once administered.
  The first three patients administered KCAT19 T cells must have a matched HLA cord unit available (≥4 of 6 HLA matching). Subject to approval by the trial independent Data Monitoring Committee (IDMC), subsequent patients may also be treated with the best-matched cord available even if this is HLA mismatched (≥0 of 6 HLA matching).
  Patients will be followed up on trial for up to 10 years following KCAT19 T cell administration.
  Specifically, KCAT19 aims to establish the feasibility of delivery, safety and efficacy of HLA-matched cord blood-derived KCAT19 T cells engineered to express the novel UCHT1-KDEL TCR-downregulation module (used with the aim to minimise GvHD) and CAT19 anti-CD19 CAR (to target the patient’s disease). The principle scientific aims are to establish if CAR-T in which TCR expression is reduced using UCHT1-KDEL are able to induce GvHD, are able to persist in vivo, and have anti-tumour efficacy similar to autologous (derived from the patient who will be treated rather than a donor) products.

• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  22/SC/0204

• Date of REC Opinion

  5 Sep 2022

• REC opinion

  Further Information Favourable Opinion