A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL)

An Open-Label, Multi-Centre, Phase Ib/II Study Evaluating the Safety and Efficacy of AUTO1, a CAR T Cell Treatment Targeting CD19, in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia

This is a Phase 1b/2 study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 in adult patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (ALL).

This Phase 1b/2, open-label, multi-center, single arm study is designed to evaluate the safety and efficacy of AUTO1 in adult patients with B-cell ALL by determining the overall response rate (ORR).

Adult patients with r/r ALL will be enrolled in both phases of the study. Consented patients will go through the following five sequential stages: screening, leukapheresis, pre-conditioning, treatment, and follow-up. All patients will receive a total target dose of 410E+6 of CAR T cells as a split dose on Day 1 and on Day 10 (± 2 days).

Inclusion Criteria:

• Age 18 years or older
• ECOG performance status of 0 or 1
• Relapsed or refractory B cell ALL
• Patients with Ph+ ALL are eligible if intolerant to TKI, failed two lines of any TKI, or failed one line of second-generation TKI, or if TKI is contraindicated
• Documented CD19 positivity within 1 month of screening
• Phase 1b: Primary Cohort IA: Presence of ≥5% blasts in BM at screening
• Phase 1b: Exploratory Cohort IB: MRD-positive defined as ≥ 1e-4 and <5% blasts in the BM at screening
• Phase 2: Primary Cohort IIA: Presence of ≥5% blasts in BM at screening
• Phase 2: Cohort IIB: ≥2nd CR or CRi with MRD-positive defined as ≥1e-3 by central NGS testing and <5% blasts in the BM at screening
• Adequate renal, hepatic, pulmonary, and cardiac function

Exclusion Criteria:

• Phase 1b (Cohort IA and Cohort IB) and Phase 2 (Cohort IIA and Cohort IIB) B-ALL with isolated EM disease
• Diagnosis of Burkitt's leukaemia/lymphoma or CML lymphoid in blast crisis
• History or presence of clinically relevant CNS pathology
• Presence of CNS-3 disease or CNS-2 disease with neurological changes
• Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management
• Active or latent Hepatitis B virus or active Hepatitis C virus
• Human Immunodeficiency Virus (HIV), HTLV-1, HTLV-2, syphilis positive test
• Prior CD19 targeted therapy other than blinatumomab. Patients who have experienced Grade 3 or higher neurotoxicity following blinatumomab.