CAR T-Cells for B-Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Antiseizure, Corticosteroids

Disqualifiers: HIV, Active hepatitis, CNS disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using specialized cells, called CAR T-cells (CD19.20.22 CAR T cells), to manage B-cell lymphoma that hasn't responded to other treatments. The researchers aim to determine if these cells are safe, effective, and persist long enough in the body to make a difference. Individuals with B-cell lymphoma, which has returned or not improved after at least two treatments, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) required for some treatments before participating, such as 3 months for prior Auto CAR T and Bispecific T-Cell Engager, and 1 month for prior Allo CAR T.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that treatments combining CD19 with CD22 or CD20, like the CAR T-cells under study, hold promise for treating blood cancers. These treatments are generally safe, though some patients have experienced side effects.

For example, studies of similar treatments reported side effects such as fever and low blood pressure, which are common with CAR T-cell therapies. Importantly, these studies demonstrated that such side effects can be managed with proper care.

As this treatment is in an early trial phase, researchers are closely monitoring safety. However, the use of similar CAR T-cell therapies suggests that some level of safety is already understood. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the CD19.20.22 CAR T-cell treatment for B-cell lymphoma because it offers a personalized approach by modifying a patient's own T-cells to target multiple antigens on cancer cells. Unlike traditional treatments, such as chemotherapy and radiation, which can harm healthy cells, CAR T-cells are engineered to specifically attack cancer cells, potentially leading to fewer side effects. Additionally, this treatment targets three different markers (CD19, CD20, and CD22) on B-cell lymphoma cells, increasing the chances of effectively eliminating cancer cells even if they try to evade single-target therapies. This multi-target approach could provide a more robust and long-lasting response, which is why it's generating so much excitement among researchers.

What evidence suggests that this treatment might be an effective treatment for B-cell lymphoma?

Research shows that CAR T-cell therapy, which targets the CD19 protein, has greatly benefited patients with relapsed or hard-to-treat B-cell lymphoma. Studies have found significant health improvements in patients receiving these CD19-targeted CAR T-cells. Targeting both CD19 and CD20 yields even better results, with higher success rates after three months compared to targeting CD19 alone. Additionally, CAR T-cells targeting CD19 and CD22 have demonstrated promising long-term results, with more than half of the patients experiencing a year without disease progression. In this trial, participants will receive CAR19.20.22 T-cells, which aim to enhance treatment by targeting three proteins: CD19, CD20, and CD22, building on these encouraging findings. ^{1 2 4 6 7}

Who Is on the Research Team?

Djordje Atanackovic, MD

Principal Investigator

Professor of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with various types of B-cell lymphomas that have come back or haven't responded to treatment. It's specifically for those whose cancer cells show at least two target antigens that the CAR T-cells are designed to attack.

Inclusion Criteria

I am 18 years old or older.

Two out of three target antigen expression required on the most recent biopsy 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. Cardiac ejection fraction (EF) ≥ 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 > 30 mL/min. Subjects must have the following hematologic function parameters: Absolute neutrophil count (ANC) > 1000/µL. Absolute Lymphocyte Count > 100/µL. Platelets > 50,000/µL. 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.

My lymphoma can be measured by scans, and I have at least one lymph node larger than 1.5 cm.

Exclusion Criteria

I am unable to understand and give consent for treatment.

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 may impair the ability to evaluate neurotoxicity. Active systemic fungal, viral or bacterial infection. Pregnant or breast-feeding woman. Previous or concurrent malignancy with 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. Baseline dementia that would interfere with therapy or monitoring. 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 specific criteria must be met. ECOG 2 or higher (unless due to lymphoma diagnosis). Ongoing immunosuppression for graft versus host disease treatment or prophylaxis. History of a severe hypersensitivity reaction or contraindication to any of the agents used in the study. Subjects of both genders who are not willing to practice highly effective birth control. 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo fludarabine/cyclophosphamide lymphodepletion prior to CAR T-cell infusion

1 week

Treatment

Participants receive CAR19.20.22 T-cells infusion at various dose levels

Up to 24 months

Follow-up

Participants are monitored for safety, efficacy, and persistence of CAR T-cells

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• CD19.20.22 CAR T cells

Trial Overview The study tests a new therapy using tri-specific CAR T-cells (CD19.20.22) alongside chemotherapy drugs Fludarabine and Cyclophosphamide in patients with relapsed/refractory B-cell lymphoma, aiming to evaluate safety, effectiveness, cell persistence, and exhaustion levels.

How Is the Trial Designed?

Group I: Dose Level 1 Experimental Treatment 2 Interventions

Autologous CAR19.20.22 T-cells, 2.5 × 10\^6 cells/kg (±20%), IV infusion following fludarabine/cyclophosphamide lymphodepletion.

Group II: Dose Level 0 Experimental Treatment 2 Interventions

Autologous CAR19.20.22 T-cells, 1.0 × 10\^6 cells/kg (±20%), IV infusion following fludarabine/cyclophosphamide lymphodepletion.

Group III: Dose Level -1 Experimental Treatment 2 Interventions

Autologous CAR19.20.22 T-cells, 0.75 × 10\^6 cells/kg (±20%), IV infusion following fludarabine/cyclophosphamide lymphodepletion.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07168486

Study Details | NCT07168486 | CD19.20.22 CAR T-cells ... The goal of this study is to treat patients diagnosed with relapsed or refractory positive B cell lymphoma - positive for 2 or more target ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427354/

CD19 CAR-T Outcomes in Patients with Relapsed/Refractory ... In this real-world study, CD19 CAR-T-cell therapy in patients with R/R DLBCL resulted in meaningful clinical benefits, particularly in those ...

3. mdanderson.org mdanderson.org/newsroom/researchers-identify-key-b-cell-lymphoma-traits-linked-with-greatest-benefit-from-CD19-CAR-T-cell-therapy.h00-159777234.html

Researchers identify key B-cell lymphoma traits linked with ... Researchers identify key B-cell lymphoma traits linked with greatest benefit from CD19 CAR T cell therapy. MD Anderson News Release June 18 ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1582944/full

Comparison of efficacy and adverse effects of CD19/20 ... Results: The CD19/20 CART group demonstrated significantly superior three-month efficacy to the CD19 CAR T-cell group, with a notably higher ...

5. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06567-3

Efficacy and safety of a novel CD19, CD22 dual-targeted ... The 12-month PFS rate was 54.66%, and the 12-month OS rate was 77.34%. The 24-month PFS rate was 49.69% and the 24-month OS rate was 72.51%.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12106392/

Efficacy and safety of CD19 combined with CD22 or CD20 ... CD19 combined with CD22 or CD20 therapy is a promising immunotherapy approach for the treatment of hematological malignancies.

7. mdpi.com mdpi.com/2673-6357/6/1/3

Real-World Outcomes of Anti-CD19 Chimeric Antigen ... We report on 82 patients with R/R DLBCL that successfully completed an infusion of an anti-CD19 CAR T-cell product at our institution.