Cluster of Differentiation Antigen 19/22(CD19/22) CAR T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma

NCT03287817 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: AUTO3-DB12016-004682-11
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 11

Brief Summary

The purpose of this study is to test the safety and efficacy of AUTO3, a CAR T cell treatment targeting CD19 and CD22 with consolidation or pre-conditioning with anti-PD1 antibody in patients with DLBCL

Conditions

Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Keywords

Diffuse Large B Cell Lymphoma; Relapsed Diffuse Large B Cell Lymphoma; Refractory Diffuse Large B Cell Lymphoma; AUTO3; PD-1; Anti PD-1 antibody

Outcome Measures

Primary Outcomes (3)

• Phase I Escalation - Safety (Number of Participants With Grade 3-5 Toxicities) and Identification of Recommended Phase II Dose and Schedule (RP2D).

  Number of patients with Grade 3-5 toxicities during escalation part of Phase I (Cohorts: 50x10\^6 CD19/22 CAR+ T Cells; 50x10\^6 CD19/22 CAR+ T Cells+Pembrolizumab \[Pem\] Day 14; 150-450x10\^6 CD19/22 CAR+ T Cells+Pem Day 14; 150-450x10\^6 CD19/22 CAR+ T Cells+Pem Day -1 in Inpatient Setting) Dose-limiting toxicity defined as: * New non-hematological AE Grade \>=3 using NCI CTCAE (5.0), probably/definitely related to AUTO3, occurring in DLT evaluation period, which did not resolve to Grade 2 or better in 14 days, despite supportive measures. * Grade 4 CRS, neurotoxicity (NT), or cerebral edema, or Grade 3 NT that lasted \>72 hrs * Grade \>3 Disseminated Intravascular Coagulation * Grade \>2 Infusion Reaction with AUTO3 * Grade 4 or 5 event not managed with conventional supportive measures or necessitating dose reduction or modification to trial therapy * Any event that in opinion of Investigator and/or medical monitor put patient at undue risk could also have been considered DLT

  Within 75 days of AUTO3 infusion

• Phase I Expansion - Safety (Incidence of Grade 3-5 Toxicities) in the Outpatient / Ambulatory Care Setting

  The incidence of Grade 3-5 toxicities during the expansion part of Phase I (Dose cohort: 150 to 450 x 10\^6 CD19/CD22 CAR-positive T Cells + Pembrolizumab at Day -1 in an Outpatient Setting)

  Within 75 days of AUTO3 infusion

• Phase II - Overall Response Rate as Per Lugano Criteria

  This was not analysed due to study termination prior to initiation of Phase II. End of study notification submitted to Medicines and Healthcare products Regulatory Agency (MHRA) (reference 46113/0003/001-0016) - The Last patient last visit was 19 October 2023 (at end of Phase 1) and the study is considered completed (End of study). As per protocol v10.0, end of study is defined as 36 months after the last patient has received AUTO3 infusion or earlier in the event of death or consent withdrawal. Fifty-two patients received AUTO3 in the Phase I part of the study. After reviewing the data and taking into consideration the available treatment landscape in r/r DLBCL, Autolus didn't progress AUTO3-DB1 into the Phase II part of the study. Autolus notified MHRA on 08 November 2021 about enrolment to Phase II of the study (Autolus has decided not to progress AUTO3-DB1 into the Phase II part of the study), and MHRA acknowledged it on 09 November 2021.

  Up to 2 years

Secondary Outcomes (5)

• Feasibility of Generating AUTO3: Number of Patients' Cells Successfully Manufactured as a Proportion of the Number of Patients Undergoing Leukapheresis.

  Up to 8 weeks post leukapheresis.

• Determine the Complete Response Rate Following Treatment With AUTO3, as Per Lugano Criteria.

  Up to 2 years

• Duration of Response (DOR).

  Up to 2 years

• Progression-free Survival (PFS).

  Up to 2 years

• Overall Survival (OS).

  Up to 2 years

Other Outcomes (3)

• To Determine the Expansion and Persistence of AUTO3 Following Adoptive Transfer in Different Lymphoma Subtypes (Maximum Concentration)

  Up to 2 years

• To Determine the Expansion and Persistence of AUTO3 Following Adoptive Transfer in Different Lymphoma Subtypes (Area Under the Curve From Day 0 to Day 28)

  Up to 2 years

• To Determine the Expansion and Persistence of AUTO3 Following Adoptive Transfer in Different Lymphoma Subtypes (Time to Maximum Concentration)

  Up to 2 years

Study Arms (1)

AUTO3

EXPERIMENTAL

Patient with relapsed or refractory DLBCL

Biological: AUTO3

Interventions

AUTO3 BIOLOGICAL

Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 50 x 10⁶ to 900 x 10⁶ CD19/ CD22 Chimeric Antigen Receptor (CAR) positive T cells with limited duration of anti-PD1 antibody (pembrolizumab).

AUTO3

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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
• Histologically confirmed DLBCL and large B cell lymphoma subsets, including:
• Phase I and Phase II Cohort 1:
• DLBCL, not otherwise specified (NOS), per World Health Organisation classification and DLBCL with MYC oncogene (MYC) and B cell lymphoma 2 (BCL2) gene and/or B cell lymphoma 6 (BCL6) gene rearrangements (double/triple hit).
• Transformed DLBCL from follicular lymphoma (FL).
• High-grade B cell lymphoma with MYC expression (excluding Burkitt's lymphoma) Phase I and Phase II Cohort 2.
• Transformed DLBCL from other indolent lymphomas (excluding Richter's transformation).
• Primary mediastinal large B cell lymphoma.
• Chemotherapy-refractory disease, defined as one or more of the following:
• Stable disease (≤12 months) or progressive disease as best response to most recent chemotherapy containing regimen. Refractory disease after frontline chemo-immunotherapy is allowed.
• Disease progression or recurrence in ≤12 months of prior autologous haematopoietic stem cell transplantation (ASCT).
• Relapse after ≥two lines of therapy or after ASCT. At a minimum:
• Patients must have received rituximab or another anti-cluster of differentiation antigen 20 (CD20) monoclonal antibody (unless Investigator determines that tumour is CD20-negative) and an anthracycline-containing chemotherapy regimen.

You may not qualify if:

• Prior allogeneic haematopoietic stem cell transplant.
• Females who are pregnant or lactating.
• History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
• Patients with active CNS involvement by malignancy. Patients with history of central nervous system (CNS) involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to AUTO3 infusion).
• Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event.
• Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded).
• Evidence of pericardial effusion
• 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.
• Patients with any major surgical intervention in the last 3 months.
• Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis.
• History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS.
• Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis.
• History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed).

Sponsors & Collaborators

• Autolus Limited: lead

Study Sites (11)

City of Hope Hospital

Duarte, California, 91010, United States

Location

Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center/Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Sylvester Comprehensive Cancer Center / University of Miami

Miami, Florida, 33136, United States

Location

Siteman Cancer Center / Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

TriStar Centennial Medical Center /Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

St David's South Austin Medical Center /Sarah Cannon Research Institute

Austin, Texas, 78704, United States

Location

The Beatson West of Scotland Cancer Centre / Queen Elizabeth University Hospital

Glasgow, G12 0YN, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Location

Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

Related Publications (2)

• Roddie C, Lekakis LJ, Marzolini MAV, Ramakrishnan A, Zhang Y, Hu Y, Peddareddigari VGR, Khokhar N, Chen R, Basilico S, Raymond M, Vargas FA, Duffy K, Brugger W, O'Reilly MA, Wood L, Linch DC, Peggs KS, Bachier C, Budde EL, Lee Batlevi C, Bartlett N, Irvine D, Tholouli E, Osborne W, Ardeshna KM, Pule MA. Dual targeting of CD19 and CD22 with bicistronic CAR-T cells in patients with relapsed/refractory large B-cell lymphoma. Blood. 2023 May 18;141(20):2470-2482. doi: 10.1182/blood.2022018598.

  PMID: 36821767 RESULT

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Only results of Phase I of the study are presented due to study termination prior to initiation of Phase II.

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

Model Details: A dose escalation and expansion phase (Phase I) followed by Phase II

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 19, 2017
• Study Start: September 5, 2017
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: July 14, 2025
• Results First Posted: July 14, 2025

Record last verified: 2025-06

Locations

GB (4); US (7)