NCT07168486
CD19.20.22 CAR T-cells for Patients With Relapsed/Refractory B-Cell Lymphomas
Enrolling by Invitation
PHASE1Ages 18+InterventionalTreatmentUniversity of Maryland, BaltimoreInvestigator-initiated
~15 participants
Updated 2025-09-11 on ClinicalTrials.gov
What's tested:CD19.20.22 CAR T cellsFludarabine and Cyclophosphamide
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Safety and Tolerability]
Measured over From date of enrollment assessed up to 24 months
+3 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Djordje Atanackovic, MD · PRINCIPAL_INVESTIGATOR · Professor of Medicine
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Age ≥ 18 years
Histologically confirmed relapsed/refractory B cell Lymphoma. Histologies allowed: diffuse large B cell lymphoma (DLBCL), primary mediastinal large B cell lymphoma (PMBCL), Follicular Lymphoma (FL), transformed follicular lymphoma (tFL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Richter's transformation with or without concurrent CLL, Burkitt's lymphoma.
Relapsed or Refractory disease after two lines or more of therapy (except one or more line for MCL) including rituximab and other anti-CD20 antibodies, BTK inhibitors (Mantle Cell Lymphoma only), and anthracycline (specifically for DLBCL, PMBCL, tFL, and Burkitt's lymphoma).
Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma \[2\]. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. If the only measurable disease is lymph node disease, at least 1 lymph node should be ≥ 1.5 cm.
Two out of three target antigen expression required (IHC or flow per institutional guidelines) on the most recent biopsy available. We will analyze a tumor sample from the most recent relapse or development of refractory disease state (archival sample within \<6 months) for antigen expression. Alternatively, a new biopsy will be obtained in case archival material is not available.
Prior Auto CAR T permitted (washout 3 months)
Prior ASCT is permitted and prior AlloSCT is permitted if off immunosuppression and no clinically significant (more than grade 1) GVHD
Prior Allo CAR T permitted (washout 1 month, permitting hematologic parameters)
Prior Bispecific T-Cell Engager (BiTE) permitted (washout 3 months)
At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint (ICP) therapy and anti-CD20 mAb therapy
At least 3 half-lives must have elapsed after any prior systemic inhibitory/stimulatory ICP or anti-CD20 mAb therapy at the time the subject is planned for leukapheresis
ECOG 0 or 1
Acceptable Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion) Cardiac ejection fraction (EF) greater than or equal to 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA) Resting O2 saturation \>90% on room air Total bilirubin ≤ 1.5 mg/dL except in individuals with Gilbert's syndrome Total bilirubin ≤ 3.0 mg/dL in individuals with Gilbert's syndrome Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \<5 times the Upper Limit of Normal (ULN) for age
A creatinine clearance (as estimated by direct urine collection or the non-racial CKD-EPI equation) \> 30 mL/min
Subjects must have the following hematologic function parameters:
Estimated life expectancy of more than 3 months independent from primary disease
Subjects of child-bearing or child-fathering potential must be willing to use study-defined highly-effective methods birth control from the time of enrollment on this study through the study follow-up period Study-defined highly-effective methods of birth control are implants, levonorgestrel releasing intrauterine systems, medroxyprogesterone acetate depot, tubal sterilization, sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses), and ovulation inhibitory progesterone.
Exclusion
Unable to give informed consent
Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive), If there is a history of treated hepatitis B or hepatitis C, the viral load must be polymerase chain reaction (PCR) negative; antiviral secondary prophylaxis is required if HBsAg negative and anti-HBc positive
Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing
Known history of active seizure or presence of seizure activities or on active anti-seizure medications within the prior 12 months
Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease
Presence of active CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity
Active systemic fungal, viral or bacterial infection
Pregnant or breast-feeding woman
Previous or concurrent malignancy with the following exceptions:
Medical condition requiring prolonged use of systemic corticosteroids equivalent to Prednisone \>10 mg/day
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion).
For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.
Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline.
History of severe immediate hypersensitivity reaction to any of the agents used in this study
Clinical suspicion of central nervous system (CNS) lymphoma
If the subject has history of CNS disease, then he/she must Have no signs or symptoms of active CNS disease Have no active disease on magnetic resonance imaging (MRI)- e.g. vasogenic edema; stable, post-treatment changes are acceptable.
In case of cerebral vascular accident (CVA) The CVA event must be \> 12 months prior to leukapheresis Any neurological deficits must be stable
ECOG 2 or higher (unless due to lymphoma diagnosis)
Ongoing immunosuppression for graft versus host disease treatment or prophylaxis (prior allogeneic stem cell transplant permitted)
History of a severe hypersensitivity reaction or contraindication to any of the agents used in the study (including fludarabine and cyclophosphamide).
Subjects of both genders who are not willing to practice highly effective birth control from the time of informed consent through 6 months after the CAR19.20.22infusion
In the investigator's judgment, the subject is unlikely to complete all study-specific visits or procedures, including follow-up visits, or comply with the study requirements for participation
What this trial measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Safety and Tolerability]From date of enrollment assessed up to 24 months
To evaluate the safety and tolerability of CAR19.20.22 CAR T-cells
- Efficacy Overall Response Rate in participantsFrom date of enrollment assessed up to 24 months
Effect on the disease: Number of patients with clinical responses: Overall Survival (OS); Progression-Free Survival (PFS); Overall Response Rate (ORR)
- Change in CAR19.20.22 T-cell function assessed by multicolor ELISPOT assay using CD19/CD22 protein targets.From date of enrollment assessed up to 24 months
Function will be assessed using in-house multicolor ELISPOT assays performed on leukapheresis product, starting T-cells, final CAR T-cell product, and post-infusion blood samples. To evaluate the functionality of the CAR T-cells over time using our in-house developed multicolor enzyme-linked immune absorbent spot (ELISPOT) assays using beads covered with CD19 and CD22 recombinant proteins as targets.
- Persistence of CAR19.20.22 T-cells in peripheral blood measured by qPCR vector copy number and flow cytometry enumeration of CD19 and CD22 CAR-expressing T-cells."From date of enrollment assessed up to 24 months
PK/PD persistence will be evaluated using qPCR to quantify vector copy number and flow cytometry to enumerate CD19 and CD22 CAR-expressing T-cells. Pharmacokinetics/Pharmacodynamics (PK/PD) - In vivo duoCAR T-cell persistence in peripheral blood samples by qPCR to measure vector copy number or Flow Cytometry to enumerate CD19 CAR or CD22 CAR expressing T-cells.