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
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).
Objective
Phase Ib Primary Objective:
-to evaluate the safety of AUTO1
Phase II: Primary Objective
-to evaluate the clinical efficacy of AUTO1
Phase Ib Secondary Objectives:
-to evaluate the feasibility of manufacturing and administering AUTO1
-to evaluate the clinical efficacy of AUTO1
-to evaluate the expansion and persistence of AUTO1
Phase II Secondary Objectives:
-to evaluate the clinical efficacy of AUTO1
-to assess the safety and tolerability of AUTO1
-to evaluate the feasibility of manufacturing and administering AUTO1
-to evaluate the expansion and persistence of AUTO1
-to evaluate the duration of B cell aplasia
-to evaluate Patient Reported Outcome and Quality of Life
-to evaluate health care resource utilization for the management of AUTO1 related toxicity
Exploratory Objectives:
-to determine the proportion of patients who achieve MRD-negative CR using next generation sequencing
-to determine ORR and DoR in patients who have received prior blinatumomab
-to determine ORR in patients with ≤20% and >20% blasts prior to pre-conditioning as assess by IRRC
-to determine the time course and magnitude of cytokine release evaluated using an appropriate assay
-to assess antibody and/or T cell mediated immune responses against AUTO1
-to characterize the relationship between the CAR-T cell phenotype/genomics and persistence in vivo
-seek any relationship between parameters of activity and tumor burden (e.g. % blast cells in BM, or EM site), level of CD19 expression (flow cytometry or immunohistochemistry [IHC]), CAR T cell phenotype
-seek any relationship between incidence and severity of CRS, neurotoxicity, or other toxicity and tumour burden (e.g. % blast cells in BM, or EM site), level of CD19 expression (IHC or flow cytometry), CAR T Cell phenotype
-to evaluate CSF for cytokine and CAR T cell levels in patients experiencing neurologic toxicity whenever feasible
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 > Phase II: Primary Cohort IIA: Presence of >5% blasts in BM at screening
Phase II: Exploratory Cohort IIB: MRD-positive defined as >1E-4 and > Adequate renal, hepatic, pulmonary, and cardiac function
Phase Ib (Cohort IA and Cohort IB) and Phase II Cohort IIA only 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.
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