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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Autolus Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Dec 2021 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-512903-38-00

EudraCT number

2019-001937-16

ClinicalTrials.gov

NCT04404660

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

- To evaluate the safety of AUTO1.
- To evaluate the clinical efficacy of AUTO1.

Secondary objectives 5

1. To evaluate the clinical efficacy of AUTO1.
2. To assess the safety and tolerability of AUTO1.
3. To evaluate the feasibility of manufacturing and administering AUTO1.
4. To evaluate the expansion and persistence of AUTO1.
5. To evaluate the duration of B cell aplasia.

Conditions and MedDRA coding

Relapsed or refractory B cell acute lymphoblastic leukaemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age 18 years or older.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Relapsed or refractory CD19-positive B-ALL
4. 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.
5. In patients treated with blinatumomab, CD19 expression should be confirmed after blinatumomab therapy has been stopped.
6. Adequate renal, hepatic, pulmonary, and cardiac function

Exclusion criteria 4

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion.
2. 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)

Secondary endpoints 5

1. 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.
2. Frequency and severity of AEs and SAEs. Incidence and duration of severe hypogammaglobulinaemia.
3. Proportion of enrolled patients for whom an AUTO1 product can be manufactured and administered.
4. Detection of CAR T cells measured by PCR in the peripheral blood and BM following AUTO1 infusion.
5. Depletion of circulating B cells assessed by flow cytometry in the peripheral blood.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Autolus Limited

Sponsor organisation

Autolus Limited

Address

191 Wood Lane

City

London

Postcode

W12 7FP

Country

United Kingdom

Scientific contact point

Organisation

Autolus Limited

Contact name

Ram Malladi

Public contact point

Organisation

Autolus Limited

Contact name

Ram Malladi

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications