Preliminary Safety and Tolerability of CD19x22 CAR T Cells in Adolescent and Adult R/R B-NHL Patients

Recruiting now · Phase 1

Conditions studied: Non-Hodgkin Lymphoma, B-cell Non-Hodgkin Lymphoma (B-NHL), Mantle Cell Lymphoma (MCL), CNS Lymphoma

In brief

This open-label, single arm phase 1 trial aims to determine the safety and tolerability of anti-CD19 and anti-CD22 chimeric antigen receptor-expressing (CAR) T cells (CD19x22 CAR T) in adolescents and adults with relapsed/refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL). This trial will determine the maximum tolerated dose of CD19x22 CAR T cells using a standard 3+3 trial design.

Key facts

Study ID: NCT05098613
Run by: University of Colorado, Denver
People needed: 68
Starts: 2021-12-21
Expected to finish: 2027-12-01
Last updated by the study team: 2026-07-09

Who can join

Age: 16 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age: ≥ 16 years of age with no upper age limit. (NOTE: the first three subjects on this trial must be ≥ 18 years of age.)
COHORT 1: Non-CNS B-NHL
Histologically confirmed aggressive B-cell NHL including the following types defined by World Health Organization (WHO) 2008:
Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr Virus (EBV)+ DLBCL of the elderly; OR
Primary mediastinal (thymic) large B cell lymphoma; OR
Transformation to DLBCL; OR
High grade B-cell Lymphoma (HGBL).
Subjects must not have any signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at screening; subjects who have been previously treated for CNS disease, but have no evidence of disease at screening are eligible for this cohort.
Subjects must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least two lines of therapy.
The two lines of prior therapy must include an anthracycline and anti-CD20 monoclonal antibody treatment.
Relapse or refractory after single antigen targeting CAR T cell therapy
Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
COHORT 2: MANTLE CELL LYMPHOMA (MCL)
Mantle Cell Lymphoma (MCL).
Results of all tests conducted on the tissue at initial diagnosis and/or relapse, including, but not limited to, the MCL subtype (classic and blastoid), Ki-67 proliferation index, and TP53 mutation status should be provided if done.
Subjects must have relapsed and/or refractory MCL confirmed by either flow cytometry or immunohistochemistry (ICH), disease stabilization, or disease recurrence after at least two lines of therapy including any combination of the agents below:
An anti-CD20-directed therapy
A BTK inhibitor
Anthracycline or Bendamustine
Relapse or refractory after single antigen targeting CAR T cell therapy.
Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. MCL patients without measurable nodal or extranodal disease by IWG criteria are eligible if they have bone marrow involvement of MCL at relapse
COHORT 3: PRIMARY CNS LYMPHOMA OR SECONDARY CNS LYMPHOMA
Subjects with relapsed and/or refractory primary CNS lymphoma (PCNSL) OR secondary CNS lymphoma (SCNSL), as defined by the following:
a. Absence of measurable disease outside the CNS, as determined by radiographic imaging (i.e. PET/CT).
b. Detectable CNS disease, as defined as: i. At least 1 site of measurable disease within the brain or spinal cord that is ≥ 1 cm in the longest diameter based on MRI or PET/CT imaging; OR, ii. CSF-positive disease only (confirmed by presence of persistent disease, detected by cytology or flow cytometry) at the time of enrollment iii. Neoplastic B-cells detectable within the vitreous by flow cytometry or cytology

You may not qualify if…

Age < 16 years of age.
Patients who are intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
Patients with active, poorly controlled hydrocephalus defined as increase/worsening in symptoms (headaches, nausea/vomiting, lethargy, or neurological function with increased hydrocephalus noted on radiologic evaluation and/or need for CSF diversion. Note: If hydrocephalus is controlled after CSF diversion, patient may be eligible for the study. Only applicable to Cohort 3.
Patients with brainstem lesions. Only applicable to Cohort 3.
History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ and localized prostate cancer not on active treatment.
Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if responding to active treatment.
Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen [HBsAg] positive) or hepatitis C.
History of known myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular lymphoma involvement.
Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or efficacy of study treatment.
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
Pregnancy (serum pregnancy test must be obtained at time of enrollment for females of childbearing potential and to be repeated 72 hours prior to lymphodepleting chemotherapy regimen); females who have undergone surgical sterilization or who have been postmenopausal for at least 6 months are not considered to be childbearing potential.
Lactating.
In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
Unwilling to participate in long-term follow-up protocol that is required if CAR T cell therapy is administered at CU Anschutz.
APHERESIS ELIGIBILITY
In order to proceed with apheresis, enrolled participants cannot have active, severe infection. For the purpose of this trial, active, severe infection is defined as:
Positive blood culture within 48 hours of the start of the apheresis procedure, OR
Fever >38.2°C AND clinical signs of infection within 48 hours of start of apheresis procedure
Additionally, participants should have the following labs within 14 days of apheresis:
CBC with manual differential
Lymphocyte enumeration (TBNK) panel to measure CD3 count
CD3 count must be >0.15 x 106 cells/mL
LYMPHODEPLETING CHEMOTHERAPY ELIGIILITY:
In order to proceed with lymphodepleting chemotherapy, enrolled participants must meet all eligibility criteria below within 72 hours prior to lymphodepletion, unless otherwise specified:

Where it is running

University of Colorado Hospital — Aurora, Colorado, United States (enrolling)

Full record on ClinicalTrials.gov

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