Clinical trial NCT04404660: A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia
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
Lead sponsor: Autolus Limited
Sponsor class: INDUSTRY
First posted: 2020-05-27
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Phase Ib - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion
timeFrame: Up to 24 months
measure: Phase II - Cohort IIA: ORR defined as proportion of patients achieving CR or CRi as assessed by an IRRC.
timeFrame: Up to 24 months
Secondary outcomes:
measure: Phase II - Proportion of patients achieving MRD-negative CR by NGS (<1e-4 leukemic cells)
timeFrame: Up to 24 months
measure: Phase II - Complete remission rate
timeFrame: Up to 24 months
measure: Phase II - Response to AUTO1 treatment measured as duration of remission (DOR)
timeFrame: Up to 24 months
measure: Phase II - Response to AUTO1 measured as progression-free survival (PFS).
timeFrame: Up to 24 months
measure: Phase II -Response to AUTO1 treatment measured as overall survival (OS)
timeFrame: Up to 24 months
measure: Phase II - Frequency and severity of AEs and SAEs
timeFrame: Up to 24 months
measure: Phase II - Incidence of severe hypogammaglobulinaemia
timeFrame: Up to 24 months
measure: Phase II - Duration of severe hypogammaglobulinaemia
timeFrame: Up to 24 months
measure: Phase II - Detection of CAR T cells measured by PCR following AUTO1 infusion
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Health (UCSD)
state: California
city: Sacramento
country: United States
facility: University of California Davis (UC Davis)
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute (CBCI)
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: TriStar Centennial Medical Center (SCRI)
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: TTI-Methodist (Texas Transplant Institute) (SCRI)
state: Texas
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
city: Barcelona
country: Spain
facility: Fundacio' Hospital Universitari Vall d'Hebron
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario La Fé
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Cambridgeshire
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
state: Greater London
city: London
country: United Kingdom
facility: King's College Hospital
state: Greater London
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary Hospital
state: Greater Manchester
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
state: Scotland
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust
state: Tyne and Wear
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: West Midlands
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust (UHBW)
Study officials:
References: