Phase I/II Study Evaluating AUTO4 in Patients With T Cell Receptor Beta Constant (TRBC)1 Positive T Cell Lymphoma

NCT03590574 | Terminated Phase 1 Results DMC

• 2 other identifiers: AUTO4-TL12017-001965-26
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of this study is to test the safety and efficacy of AUTO4 a chimeric antigen receptor (CAR) T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin Lymphoma (NHL).

Conditions

T Cell Non-Hodgkin Lymphoma; Angioimmunoblastic T-cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Anaplastic Large Cell Lymphoma

Keywords

T cell lymphoma; Relapsed T cell Non-Hodgkin Lymphoma; Refractory T cell Non-Hodgkin Lymphoma; AUTO4

Outcome Measures

Primary Outcomes (2)

• The Numbers of Patients With Grade 3 to 5 Toxicity Occurring Within 60 Days of AUTO4 Infusion.

  To assess the safety and tolerability of AUTO4 administration. The incidence of Grade 3-5 toxicities occurring within 60 days of AUTO4 infusion.

  60 days of AUTO4 infusion

• Frequency of Dose-limiting Toxicity (DLT) of AUTO4 Within 28 Days of AUTO4 Infusion.

  To identify the recommended Phase II dose and maximum tolerated dose (MTD), if an MTD exists, of AUTO4 by monitoring the frequency of DLT of AUTO4 within 28 days of AUTO4 infusion.

  28 days of AUTO4 infusion

Secondary Outcomes (11)

• Frequency and Severity of All Adverse Events (AEs) and Serious Adverse Events (SAEs).

  24 months post treatment

• To Assess the Overall Safety and Tolerability of AUTO4.

  24 months post treatment

• Feasibility of Generating AUTO4: Number of Patients Whose Cells Achieve Successful AUTO4 Manufacture as a Proportion of the Number of Patients Undergoing Leukapheresis.

  Up to 8 weeks post leukapheresis

• Determine the Complete Response (CR) Rate Following Treatment With AUTO4.

  Up to 24 months

• Evaluate Duration of Response (DOR) Following Treatment With AUTO4.

  Up to 24 months

Study Arms (1)

AUTO4

EXPERIMENTAL

Relapsed or refractory T cell non-Hodgkin Lymphoma patients

Biological: AUTO4

Interventions

AUTO4 BIOLOGICAL

AUTO4 (Ritux-QBEND/10-Ritux-CD8 sort-suicide gene generated as a marker/suicide gene for T cells \[RQR8\]/anti-T cell receptor beta constant \[aTRBC\]1 CAR T cells). Following pre-conditioning with chemotherapy (cyclophosphamide and fludarabine), patients will be treated with doses from 25 to 900 x 10\^6 RQR8/anti-TRBC1 CAR T cells in Phase I. Following dose determination patients will be treated with the selected doses of RQR8/aTRBC1 CAR T cells (AUTO4) in Phase II.

AUTO4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged ≥ 18 years.
• Willing and able to give written, informed consent to be screened for TRBC1 positive T-NHL and to enter the main study.
• Confirmed diagnosis of selected T-NHL, including:
• Peripheral T cell lymphoma not otherwise specified, or
• Angioimmunoblastic T cell lymphoma, or
• Anaplastic large cell lymphoma
• Confirmed TRBC1 positive tumour.
• Relapsed or refractory disease and have had ≥1 prior lines of therapy.
• Positron emission tomography (PET)-positive measurable disease per Lugano classification.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Adequate bone marrow function without the requirement for ongoing blood products.
• Adequate renal, hepatic, pulmonary, and cardiac function.
• For females of childbearing potential (defined as \< 2 years after last menstruation or not surgically sterile), a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment. For females who are not postmenopausal (\< 24 months of amenorrhea) or who are not surgically sterile (absence of ovaries and/or uterus), a highly effective method of contraception together with a barrier method must be used from the start of the pre-conditioning stage and for at least 12 months after the last dose of AUTO4 (study treatment). They must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 12 months after receiving the last dose of study drug
• For males, it must be agreed that 2 acceptable methods of contraception are used.
• No contra-indications for leukapheresis, or the pre-conditioning regimen.

You may not qualify if:

• Patients with T cell leukaemia.
• Females who are pregnant or lactating.
• Prior treatment with investigational gene therapy or approved gene therapy or genetically engineered cell therapy product or allogeneic stem cell transplant.
• Known history or presence of clinically relevant central nervous system (CNS) pathology. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS.
• Current or history of CNS involvement by malignancy.
• Clinically significant, uncontrolled heart disease.
• Patients with evidence of uncontrolled hypertension or with a history of hypertension crisis or hypertensive encephalopathy.
• Patients with a history (within 3 months) or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of pre-conditioning.
• Patients with active gastrointestinal bleeding.
• Active infectious bacterial, viral disease or fungal disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T cell lymphotropic virus or syphilis) requiring treatment.
• Active autoimmune disease requiring immunosuppression.
• History of other neoplasms unless disease free for at least 2 years (adequately treated carcinoma in situ, curatively treated non-melanoma skin cancer, breast or prostate cancer on hormonal therapy are allowed).
• Prior treatment with programmed cell death protein 1, programmed death ligand 1, or cytotoxic T lymphocyte-associated protein 4 targeted therapy, or tumour necrosis factor (TNF) receptor superfamily agonists including cluster of differentiation (CD)134 (OX40), CD27, CD137 (41BB), and CD357 (glucocorticoid induced TNF receptor family related protein) within 6 weeks prior to AUTO4 infusion.
• Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
• Use of rituximab (or rituximab biosimilar) within the last 6 months prior to AUTO4 infusion.

Sponsors & Collaborators

• Autolus Limited: lead

Study Sites (5)

Vall d'Hebron Institute of Oncology

Barcelona, Spain

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Manchester Royal Infirmary Hospital

Manchester, United Kingdom

Location

Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

Related Publications (1)

• Cwynarski K, Iacoboni G, Tholouli E, Menne T, Irvine DA, Balasubramaniam N, Wood L, Shang J, Xue E, Zhang Y, Basilico S, Neves M, Raymond M, Scott I, El-Kholy M, Jha R, Dainton-Smith H, Hussain R, Day W, Ferrari M, Thomas S, Lilova K, Brugger W, Marafioti T, Lao-Sirieix P, Maciocia P, Pule M. TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial. Nat Med. 2025 Jan;31(1):137-143. doi: 10.1038/s41591-024-03326-7. Epub 2024 Nov 11.

  PMID: 39528665 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell; Immunoblastic Lymphadenopathy; Lymphoma, Large-Cell, Anaplastic

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy

Limitations and Caveats

Phase 2 was not started and therefore no planned Phase 2 endpoints were available for analysis.

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Autolus Ltd

clinicaltrials@autolus.com

+44 1483 920748

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2018
• First Posted: July 18, 2018
• Study Start: August 30, 2018
• Primary Completion: December 12, 2024
• Study Completion: December 12, 2024
• Last Updated: March 16, 2026
• Results First Posted: March 16, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); ES (1)