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

Stopped early · Phase 1/Phase 2

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

In brief

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

Key facts

Study ID

NCT03287817

Run by

Autolus Limited

People needed

52

Starts

2017-09-05

Expected to finish

2023-10-19

Last updated by the study team

2025-07-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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).
• 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).

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).
• 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.

Where it is running

• Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust — Newcastle upon Tyne, United Kingdom
• City of Hope Hospital — Duarte, California, United States
• Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center/Sarah Cannon Research Institute — Denver, Colorado, United States
• Sylvester Comprehensive Cancer Center / University of Miami — Miami, Florida, United States
• Siteman Cancer Center / Washington University School of Medicine — St Louis, Missouri, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• TriStar Centennial Medical Center /Sarah Cannon Research Institute — Nashville, Tennessee, United States
• St David's South Austin Medical Center /Sarah Cannon Research Institute — Austin, Texas, United States
• The Beatson West of Scotland Cancer Centre / Queen Elizabeth University Hospital — Glasgow, United Kingdom
• University College London Hospitals NHS Foundation Trust — London, United Kingdom
• Manchester University NHS Foundation Trust — Manchester, United Kingdom

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.