Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age1-70
SponsorBeijing GoBroad Hospital

About this trial

This study is a multi-center, open-label, non-randomised, single-arm phaseⅠclinical trial to explore the safety and efficacy of FL-33 CAR T therapy for refractory/relapsed acute myeloid leukaemia. The primary endpoints are incidence and type of dose limiting toxicity within 21 days of CAR T infusion; total number, incidence and severity of adverse events (AE) 30 days after CAR T infusion. The secondary endpoints are total number, incidence and severity of AEs 30 days to 2 years after CAR T infusion; objective response rate (ORR), complete response rate (CR) and complete response with incomplete haematological recovery (CRi) by dose group at 15, 30 and 90 Days after CAR T Infusion; duration of response (DOR), progression-free survival (PFS), overall survival (OS); pharmacokinetic characteristics. The trial will use BOIN12 design to explore the optimal biological dose (OBD) of FL-33 CAR T cells for refractory/relapsed acute myeloid leukaemia. FL-33 CAR T is set at two dose levels: 5\*10\^5 (±20%) CAR-T cells/kg for dose 1 (DL-1) and 1\*10\^6 (±20%) CAR-T cells/kg for dose 2 (DL-2), and after the optimal biological dose (OBD) is determined in the dose exploration phase, the dose expansion phase will expand the trial by 6-12 cases at the OBD, enrolling up to 21-27 cases. Enrolment of more than 21 cases can be reported for analysis and the trial will be stopped when enrolment reaches 27 cases.Additionally, an independent observation group was established, comprising two sequential cohorts: a minimum of 3 subjects were enrolled starting from the lowest dose level (DL-1).

Eligibility criteria

Qualifiers

Patients who met all the inclusion criteria were eligible for enrolment.

Patients diagnosed with primary resistance acute myeloid leukemia, tumour surface antigen CD33 expression, chemotherapy relapse, extramedullary relapse, persistent residual positivity or relapse/refractory after allogeneic haematopoietic stem cell transplantation;

Age 1-70 years old;

No severe allergies;

Disqualifiers

Patients who fulfil any of the following criteria may not be enrolled.

Patients with history of allogeneic HSCT but PBMNC is not available from prior- transplant donor for preparation of CAR T cells and peripheral blood tumour load >30%; patients without history of allogeneic HSCT and peripheral blood tumour load >30%;

Intracranial hypertension or cerebral impaired consciousness;

Symptomatic heart failure or severe arrhythmia;

Trial design

Treatments tested in this trial

  • autologous FL-33 CAR T therapy
  • prior-HSCT donor-derived FL-33 CAR T therapy
  • Newly matched donor-derived FL-33 CAR T therapy
  • FL33-03 CAR-T therapy

Treatment groups

27 Participants
are divided into 4 treatment groups

Sponsors and collaborators

Beijing GoBroad Hospital

Lead sponsor

The General Hospital of Western Theater Command

Collaborator

Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai

Collaborator

Shanghai Liquan Hospital

Collaborator

Ruijin Hospital

Collaborator