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 Ib/II 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 B cell acute lymphoblastic leukemia (ALL).
Detailed description
This Phase Ib/II, 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 relapsed or refractory 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 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 Ib: Primary Cohort IA: Presence of ≥5% blasts in BM at screening * Phase Ib: Exploratory Cohort IB: MRD-positive defined as ≥ 1e-4 and \<5% blasts in the BM at screening * Phase II: Primary Cohort IIA: Presence of ≥5% blasts in BM at screening * Phase II: Cohort IIB: ≥2nd CR or CRi with MRD-positive defined as ≥1e-3 by central ClonoSEQ® NGS testing and \<5% blasts in the BM at screening * Adequate renal, hepatic, pulmonary, and cardiac function
Exclusion criteria
* Phase Ib (Cohort IA and Cohort IB) and Phase II (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 II - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC. | Up to 24 months |
| Phase Ib - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Phase II - Response to AUTO1 treatment measured as duration of remission (DOR) | Up to 24 months |
| Phase II - Response to AUTO1 measured as progression-free survival (PFS). | Up to 24 months |
| Phase II -Response to AUTO1 treatment measured as overall survival (OS) | Up to 24 months |
| Phase II - Proportion of patients achieving MRD-negative CR by NGS (<1e-4 leukemic cells) | Up to 24 months |
| Phase II - Incidence of severe hypogammaglobulinaemia | Up to 24 months |
| Phase II - Duration of severe hypogammaglobulinaemia | Up to 24 months |
| Phase II - Detection of CAR T cells measured by PCR following AUTO1 infusion | Up to 24 months |
| Phase II - Frequency and severity of AEs and SAEs | Up to 24 months |
| Phase II - Complete remission rate | Up to 24 months |
Countries
Spain, United Kingdom, United States
Outcome results
None listed