Autologous enriched T cells retrovirally transduced to express two chimeric antigen receptors targeting CD19 and CD22 for Relapsed or refractory B-cell acute lymphoblastic leukaemia

Inclusion criteria

• {"criterion_text":"- Age 18 years or older.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- Relapsed or refractory CD19-positive B-ALL\n- Patients with Philadelphia chromosome positive ALL (Ph+ ALL) are eligible if they are intolerant to or have failed two lines of any tyrosine kinase inhibitor (TKI) or one line of second-generation TKI, or if TKI therapy is contraindicated.\n- In patients treated with blinatumomab, CD19 expression should be confirmed after blinatumomab therapy has been stopped.\n- Adequate renal, hepatic, pulmonary, and cardiac function"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of Burkitt’s leukaemia/lymphoma according to World Health Organisation (WHO) classification or chronic myelogenous leukaemia lymphoid in blast crisis.\n- History or presence of clinically relevant CNS pathology\n- Presence of CNS 3 disease or CNS 2 disease with neurological changes\n- Active or latent Hepatitis B or active Hepatitis C."}

Primary endpoints

• {"endpoint_text":"- Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Cohort IIA: Overall complete remission rate (ORR) defined as proportion of patients achieving CR or CRi as assessed by an Independent Response Review Committee (IRRC). Cohort IIB: Proportion of patients achieving MRD-negative remission by central ClonoSEQ NGS testing (<10-4 leukaemic cells)","definition_or_measurement_approach":"Cohort IIA ORR measured as proportion achieving CR or CRi assessed by an Independent Response Review Committee (IRRC). Cohort IIB MRD-negative remission measured by central ClonoSEQ NGS testing (<10-4 leukaemic cells)."}

Secondary endpoints

• {"endpoint_text":"- Complete Remission Rate (CRR). CRR within 3 months post AUTO1 infusion. Proportion of patients achieving MRD-negative remission by central ClonoSEQ NGS testing (<10-4 leukaemic cells), PCR and/or flow cytometry. Duration of remission (DOR). Duration of complete remission (DOCR). Event free survival (EFS). Progression free survival (PFS). Overall survival (OS). ORR [CR+CRi] as assessed by the Investigator.","definition_or_measurement_approach":"CRR assessed within 3 months post-infusion; MRD-negative remission assessed by central ClonoSEQ NGS (<10-4), PCR and/or flow cytometry; time-to-event endpoints (DOR, DOCR, EFS, PFS, OS) measured by standard clinical assessments; ORR by investigator assessment."}
• {"endpoint_text":"- Frequency and severity of AEs and SAEs. Incidence and duration of severe hypogammaglobulinaemia.","definition_or_measurement_approach":"Adverse events and serious adverse events recorded and graded; incidence and duration of severe hypogammaglobulinaemia tracked."}
• {"endpoint_text":"- Proportion of enrolled patients for whom an AUTO1 product can be manufactured and administered.","definition_or_measurement_approach":"Proportion of enrolled patients with successful manufacture and administration of AUTO1 product."}
• {"endpoint_text":"- Detection of CAR T cells measured by PCR in the peripheral blood and BM following AUTO1 infusion.","definition_or_measurement_approach":"Detection of CAR T cells by PCR in peripheral blood and bone marrow post-infusion."}
• {"endpoint_text":"- Depletion of circulating B cells assessed by flow cytometry in the peripheral blood.","definition_or_measurement_approach":"B cell depletion measured by flow cytometry on peripheral blood samples."}

Spain

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

17-12-2024

Processing Time Days

180

Number Of Sites

3

Number Of Participants

17

Primary sponsor

Full Name

Autolus Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom