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

Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04404660
• Other study ID #: FELIX (AUTO1-AL1)
• Secondary ID: 2019-001937-16
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 4, 2020
• Est. completion date: May 2025

Study information

• Verified date: August 2023
• Source: Autolus Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 153
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia

Intervention

Biological:
• AUTO1
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).

Locations

Country	Name	City	State
Spain	Fundacio' Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario La Fé	Valencia
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust (UHBW)	Bristol
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge	Cambridgeshire
United Kingdom	Queen Elizabeth University Hospital	Glasgow	Scotland
United Kingdom	King's College Hospital	London	Greater London
United Kingdom	University College London Hospitals NHS Foundation Trust	London	Greater London
United Kingdom	Manchester Royal Infirmary Hospital	Manchester	Greater Manchester
United Kingdom	Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne	Tyne And Wear
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Baylor Scott & White Research Institute	Dallas	Texas
United States	Colorado Blood Cancer Institute (CBCI)	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Kansas	Kansas City	Kansas
United States	University of California San Diego Health (UCSD)	La Jolla	California
United States	University of Miami	Miami	Florida
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	TriStar Centennial Medical Center (SCRI)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of California Davis (UC Davis)	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	TTI-Methodist (Texas Transplant Institute) (SCRI)	San Antonio	Texas
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	H Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Autolus Limited

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ib - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion		Up to 24 months
Primary	Phase II - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC. Cohort IIB: Proportion of patients achieving MRD-negative remission by central ClonoSEQ NGS testing (<1e-4 leukemic cells)		Up to 24 months
Secondary	Phase II - Proportion of patients achieving MRD-negative CR by NGS (<1e-4 leukemic cells)		Up to 24 months
Secondary	Phase II - Complete remission rate		Up to 24 months
Secondary	Phase II - Response to AUTO1 treatment measured as duration of remission (DOR)		Up to 24 months
Secondary	Phase II - Response to AUTO1 measured as progression-free survival (PFS).		Up to 24 months
Secondary	Phase II -Response to AUTO1 treatment measured as overall survival (OS)		Up to 24 months
Secondary	Phase II - Frequency and severity of AEs and SAEs		Up to 24 months
Secondary	Phase II - Incidence of severe hypogammaglobulinaemia		Up to 24 months
Secondary	Phase II - Duration of severe hypogammaglobulinaemia		Up to 24 months
Secondary	Phase II - Detection of CAR T cells measured by PCR following AUTO1 infusion		Up to 24 months