Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia
Conditions
Keywords
B cell acute lymphoblastic leukemia, Relapsed B cell acute lymphoblastic leukemia, Refractory B cell acute lymphoblastic leukemia, ALL, AUTO1, CD19-positive CAR T cell
Brief summary
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).
Detailed description
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).
Interventions
BIOLOGICALAUTO1
Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a total target dose of 410E+6 of CD19-positive CAR T cells as a split dose on Day 1 and on Day 10 (±2 days).
Sponsors
Autolus Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion | Up to 24 months |
| Phase 2 - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC. | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Phase 2 - Proportion of patients achieving MRD-negative CR | Up to 24 months |
| Phase 2 - Complete remission rate | Up to 24 months |
| Phase 2 - Response to AUTO1 treatment measured as duration of remission (DOR) | Up to 24 months |
| Phase 2 - Response to AUTO1 measured as progression-free survival (PFS). | Up to 24 months |
| Phase 2 -Response to AUTO1 treatment measured as overall survival (OS) | Up to 24 months |
| Phase 2 - Frequency and severity of AEs and SAEs | Up to 24 months |
| Phase 2 - Incidence of severe hypogammaglobulinemia | Up to 24 months |
| Phase 2 - Duration of severe hypogammaglobulinemia | Up to 24 months |
| Phase 2 - Detection of CAR T cells measured following AUTO1 infusion | Up to 24 months |
Countries
Spain, United Kingdom, United States
Outcome results
None listed