AzTrials
AzTrials

Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)Phase 1/2ALEXANDERNCT03287817

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

A Phase 1/2 study testing AUTO3 in people with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL), run by Autolus Limited at 11 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AUTO3
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
11 sitesin 2 countries
Study dates
5 Sep 2017to 19 Oct 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 34Show fewer
  • 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).
  • OR
  • 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.
  • Patients must have either failed ASCT, or be ineligible for or not consenting to ASCT.
  • Patients with transformed DLBCL must have received at least one line of therapy after transformation to DLBCL.
  • Positron emission tomography-positive disease per Lugano classification.
  • For females of childbearing potential, 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 or surgically sterile, highly effective methods of contraception must be used during the treatment period and for at least 12 months after the last dose of study treatment.
  • For males, it must be agreed that that two acceptable methods of contraception are used.
  • Adequate renal, hepatic, pulmonary, and cardiac function defined as:
  • Creatinine clearance ≥40 cc/min.
  • Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x upper limit of normal (ULN).
  • Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome.
  • Left ventricular ejection fraction (LVEF) ≥50% (by echocardiogram [ECHO] or Multiple gated acquisition scan [MUGA]) unless the institutional lower limit of normal is lower.
  • Baseline oxygen saturation >92% on room air and ≤Grade 1 dyspnoea.
  • Patient has adequate bone marrow (BM) function without requiring ongoing blood product or granulocyte-colony stimulating factor support and meets the following criteria:
  • Absolute neutrophil count ≥1.0 × 10^9/L.
  • Absolute lymphocyte count ≥0.3 × 10^9/L (at enrolment and prior to leukapheresis).
  • Haemoglobin ≥80 g/L.
  • Platelets ≥75 × 10^9/L
  • No contra-indications for leukapheresis.

Who cannot join

  • 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).
Show all 39Show fewer
  • 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).
  • Prior treatment with PD1, programmed cell death ligand 1 (PD-L1), or cytotoxic T lymphocyte-associated protein-4-targeted therapy, or tumour necrosis factor (TNF) receptor superfamily agonists within 6 weeks prior to AUTO3 infusion.
  • Prior treatment with investigational or approved gene therapy or cell therapy products until a dose level has treated at least three patients and has been declared safe.
  • Prior CD19 or CD22 targeted therapy.
  • The following medications are excluded:
  • Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to AUTO3 administration. However, physiological replacement, topical, and inhaled steroids are permitted.
  • Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or AUTO3 infusion.
  • Cytotoxic chemotherapies within 2 weeks of AUTO3 infusion and 1 week prior to leukapheresis (2 weeks for lymphodepleting chemotherapy).
  • Antibody therapy use including anti-CD20 therapy within 2 weeks prior to AUTO3 infusion, or 5 half-lives of the respective antibody, whichever is shorter.
  • Granulocyte-colony stimulating factor less than 10 days prior to leukapheresis.
  • Live vaccine ≤4 weeks prior to enrolment.
  • Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy.
  • Prior limited radiation therapy within 4 weeks of AUTO3 infusion or within 24 weeks for definitive radiation to chest.
  • Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
  • Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine, pembrolizumab or tocilizumab.
  • Any contraindications to receive anti-PD1 antibody pembrolizumab will be excluded from cohorts requiring administration of pembrolizumab.
  • Patients, who in the opinion of the Investigator, may not be able to understand or comply with the safety monitoring requirements of the study.
  • Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial.
  • Phase I outpatient cohort:
  • Subjects who do not have caregiver support (in line with institutional outpatient transplant guidelines) for outpatient/ambulatory care setting.
  • Subjects who are staying greater than 60 minutes (or whatever is permissible per institutional outpatient transplant guidelines) from the clinical trial site at the time of treatment.
  • For AUTO3 Infusion: Patients meeting any of the following exclusion criteria must not be treated with AUTO3 or have treatment delayed until they no longer meet these criteria:
  • Severe intercurrent infection.
  • Requirement for supplementary oxygen or active pulmonary infiltrates.
  • Clinical deterioration of organ function (renal and hepatic) exceeding the criteria set at study entry.

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States7 sites

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

    Austin, Texas, 78704

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

    Denver, Colorado, 80218

  • City of Hope Hospital

    Duarte, California, 91010

  • Sylvester Comprehensive Cancer Center / University of Miami

    Miami, Florida, 33136

  • TriStar Centennial Medical Center /Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Siteman Cancer Center / Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

United Kingdom4 sites

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

    Glasgow, G12 0YN

  • University College London Hospitals NHS Foundation Trust

    London

  • Manchester University NHS Foundation Trust

    Manchester

  • Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle upon Tyne

Other trials in United Kingdom

About this study

Official title: A Single Arm, Open-label, Multi-centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO3, a CAR T Cell Treatment Targeting CD19 and CD22 With Anti Programmed Cell Death Protein 1 (PD1) Antibody in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

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

Read the detailed description

The study will consist of 2 phases, a Phase I or dose escalation and expansion phase, and a Phase II. Patients with relapsed or refractory DLBCL will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO3, a CD19 and CD22 dual targeting CAR T cell product. Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO 3 intravenously as a single dose and in addition a limited duration of treatment with an anti-PD1 antibody (either as part of the pre-conditioning regimen or consolidation). Patients will then enter a 36-month follow-up period.

Being tested
AUTO3
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
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AUTO3Biological

    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).

Study groups in NCT03287817
Study groupRoleWhat they receive
AUTO3ExperimentalPatient with relapsed or refractory DLBCL
Receives: Biological: AUTO3

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Within 75 days of AUTO3 infusion

  2. 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)

    Measured: Within 75 days of AUTO3 infusion

  3. 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.

    Measured: Up to 2 years

Secondary outcomes (5)

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

    Feasibility of product generation was examined by assessing the number of AUTO3 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients enrolled).

    Measured: Up to 8 weeks post leukapheresis.

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

    Participants achieving objective response per Lugano criteria based on independent central radiology review.

    The Lugano classification of response by 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) PET-CT:

    1. no uptake or no residual uptake (when used interim)
    2. slight uptake, but below blood pool (mediastinum)
    3. uptake above mediastinal, but below or equal to uptake in the liver
    4. uptake slightly to moderately higher than liver
    5. markedly increased uptake or any new lesion (on response evaluation) Non-progressive disease
    • complete metabolic response - score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass
    • partial metabolic response - score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size
    • stable disease or no metabolic response - score of 4 or 5 with no obvious change in FDG uptake Progressive disease score 4 or 5 in any lesion with an increase in intensity of FDG uptake from baseline (and/or

    Measured: Up to 2 years

  3. Duration of Response (DOR).

    Duration of response was defined as the time from the first observed complete response or partial response [from the first post-baseline response assessment] until the date of first progressive disease or death due to underlying cancer (primary reason for death=progressive disease), whichever occurred first.

    Only responders (patients with complete response [CR] or partial response [PR]) were included in the analysis of duration of response.

    Response defined by Lugano classification (see Outcome Measure 5). Patients with death not due to underling cancer (primary reason for death=adverse event [AE] or Other or Unknown) or who received new anti-cancer therapy other than SCT or discontinued from the study for other reason than progressive disease (PD) or who were lost to follow-up or reached the time point of analysis without a known record of progression or death had the duration of response censored at the date of last adequate disease assessment for response.

    Measured: Up to 2 years

  4. Progression-free Survival (PFS).

    The progression-free survival was defined as the time from first AUTO3 treatment until the first progression of disease or death from any cause, whichever occurred first.

    Patients who reached the time point of analysis without a known record of progression had the PFS censored at the date of last adequate disease assessment.

    Patients who received a new stem cell transplantation (SCT) were censored at the start date of this new SCT.

    Patients who received a new anti-cancer therapy or discontinued from the study for other reason than disease progression and who were lost to follow-up were censored at the date of last adequate disease assessment.

    Response defined by Lugano classification (see Outcome Measure 5).

    Measured: Up to 2 years

  5. Overall Survival (OS).

    Overall survival (OS) was defined as the time from the date of first AUTO3 treatment up to the date of death, regardless of cause of death.

    Patients alive at the time of the analysis had the OS censored at the date of last assessment when the patient was known alive.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2017
  2. Study start5 Sep 2017
  3. Primary completion19 Oct 2023
  4. Study completion19 Oct 2023

Why it stopped: After reviewing the data and taking into consideration the available treatment landscape in r/r DLBCL, Autolus didn't progress into the Phase II part of the study and submitted a Notification of End of Trial (MHRA reference 46113/0003/001-0016).

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A dose escalation and expansion phase (Phase I) followed by Phase II
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03287817
Sponsor's protocol ID
AUTO3-DB1
Other IDs
2016-004682-11, 2016
Acronym
ALEXANDER
Status last verified
Jun 2025
First submitted
11 Sep 2017
Last updated
14 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36821767

  • 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.

    PubMed 34515338

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AUTO3 in people with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL), run by Autolus Limited at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I Escalation - Safety (Number of Participants With Grade 3-5 Toxicities) and Identification of Recommended Phase II Dose and Schedule (RP2D). (time frame: Within 75 days of AUTO3 infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03287817, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in