UCD19 CAR T Cells for B-Cell Lymphoma

Overseen By Chanel Mansfield, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must not be taking: Monoclonal antibodies, Immunomodulatory drugs, Corticosteroids

Disqualifiers: Severe psychiatric illness, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for B-cell non-Hodgkin lymphoma (NHL), a cancer affecting white blood cells. Researchers use a patient's own immune cells, called T cells, to combat the cancer. They extract T cells from the patient's blood, modify them in a lab to recognize and attack the cancer, and then reintroduce them into the body. This process uses UCD19 CAR T Cells, a form of immunotherapy. Adults whose B-cell NHL has returned or stopped responding to chemotherapy may qualify. Participants should have no other available curative treatments and must meet specific health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before participating. You must not have received monoclonal antibody therapy, immunomodulatory drugs, or corticosteroids above a certain dose within 14 days before the cell collection process. Please discuss your current medications with the study team to see if they are allowed.

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

Research shows that CD19 CAR T cells, such as the UCD19 CAR T cells under study, may help treat B-cell lymphoma. In past studies, these treatments worked for patients whose B-cell lymphoma returned or didn't respond to other treatments. However, some side effects have been reported.

Common side effects include flu-like symptoms and fever, expected with this type of therapy. These occur because the treatment activates the immune system to fight cancer cells. The intensity of these side effects can vary, and some patients may experience stronger reactions. One study found that people with other conditions, like lupus, had less severe side effects compared to those with B-cell lymphoma.

This trial is in its early stages, meaning that while some safety information exists, more research is needed to fully understand how well people tolerate the treatment. Participants in this trial will provide valuable information to help determine its safety for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-Cell Lymphoma, which typically include chemotherapy and monoclonal antibodies like Rituximab, UCD19 CAR T Cells offer a novel approach by genetically modifying a patient’s own immune cells to target cancer. This treatment is unique because it uses a lentiviral vector to reprogram the patient's T cells to specifically attack lymphoma cells, enhancing precision and potentially reducing damage to healthy cells. Researchers are excited about this treatment because it represents a personalized approach that could offer long-lasting remission by enabling the patient’s immune system to continue fighting cancer long after the initial treatment.

What evidence suggests that UCD19 CAR T Cells might be an effective treatment for B-cell lymphoma?

Research has shown that a special treatment using CD19-targeted CAR T cells can lead to long-lasting remission in people with certain blood cancers, such as non-Hodgkin lymphoma. In this trial, participants will receive UCD19 CAR T Cells, which are specially modified immune cells designed to target and kill cancer cells. Studies have found that these modified cells significantly impact patients whose cancer has returned or isn't responding to regular treatments. In some trials, up to 59% of patients achieved complete remission, meaning their cancer was no longer detectable. This method has been especially promising for difficult-to-treat cases, offering hope to those with few other options. ^{2 4 6 7 8}

Who Is on the Research Team?

Michael Verneris, MD

Principal Investigator

University of Colorado Denver, Anschutz Medical Campus

Manali Kamdar, MD

Principal Investigator

University of Colorado Denver, Anschutz Medical Campus

Are You a Good Fit for This Trial?

Adults aged 18-80 with B-cell non-Hodgkin lymphoma that's come back or didn't respond to treatment may join. They must have no other cure options, be in fairly good health, and not planning pregnancy for a year post-treatment. Excluded are those with recent monoclonal antibody therapy, severe psychiatric issues, certain lung/infection conditions, prior gene/CAR T cell therapy, HIV/Hepatitis B/C infection.

Inclusion Criteria

There are no other treatments that can cure your condition, as decided by your main doctor.

You do not currently have Graft-versus-Host Disease (GvHD).

Provision of signed and dated Informed Consent form

Exclusion Criteria

You have received a type of medication called monoclonal antibody therapy within the past 14 days.

The doctor thinks that cellular therapy is not a good option for you, for any reason.

Prior therapies:

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CAR T cell infusion

Up to 1 month

CAR T Cell Infusion

Infusion of UCD19 CAR T Cells after successful manufacture and lymphodepleting chemotherapy

Day 0 (infusion)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long Term Follow Up

Long-term safety monitoring of UCD19 CAR T Cells for latent adverse reactions

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• UCD19 CAR T Cells

Trial Overview The trial is testing UCD19 CAR T Cells on adults with relapsed/refractory B-NHL. Participants' own T cells will be modified in the lab to fight cancer by adding a new gene through a weakened virus and then returned to their body via IV injection.

How Is the Trial Designed?

Group I: UCD19 CAR T Cells Experimental Treatment 1 Intervention

Participants will receive lymphodepleting chemotherapy followed by infusion of UCD19 CAR T Cells (Lentiviral Vector \[LV\] Transduced Autologous Peripheral Blood Lymphocytes

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

Anti-CD19 CAR-T cell therapy successfully achieved a complete response in a patient with relapsed/refractory follicular lymphoma, demonstrating its efficacy in treating this type of lymphoma.

The therapy not only addressed the lymphoma but also allowed for subsequent curative treatment of gastric adenocarcinoma, indicating its potential for use in patients with multiple malignancies while maintaining a good quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. Liu, J., Cao, F., Li, Z., et al.[2022]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CD19 is a highly effective target for CAR T-cell therapies, showing significant responses in patients with relapsed B-cell malignancies, particularly chronic lymphocytic leukemia and acute lymphoblastic leukemia.

While treatment with CD19-CAR T cells can lead to severe systemic inflammatory reactions, these are generally reversible with proper medical care, highlighting the importance of monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR trials. Ramos, CA., Savoldo, B., Dotti, G.[2022]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

Citations

1. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy The data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7575989/

Efficacy and safety of CD19 chimeric antigen receptor T cells ... A number of clinical studies have confirmed that anti-CD19 CAR T-cells have a significant effect on relapsed/refractory (R/R) B-cell lymphoma (14-16). Based on ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3131/533382/Outcomes-of-CAR-T-Cells-Therapy-in-High-Grade-B

Outcomes of CAR T-Cells Therapy in High-Grade B-Cell ... Approval of anti-CD19 Chimeric Antigen Receptor (CAR) T-cells for third-line aggressive lymphomas has resulted in long-term remission in up to ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19004

Long-term outcomes of CAR-T cell therapy in DLBCL. Efficacy: Complete remission occurred in 59% with a median response duration of 8.3 months. Safety profile: CRS occurred in 100% of patients, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04544592

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL Pediatric patients with refractory or multiply relapsed leukemia and lymphoma do poorly with traditional chemotherapy and have overall survival rates below 20%- ...

6. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Safety and feasibility of anti-CD19 CAR T cells with fully humanbinding domains in patients with B-cell lymphoma. Nat Med. 2020;26:270–80 ...

7. ashpublications.org ashpublications.org/blood/article/146/9/1088/537757/Comparison-of-the-safety-profiles-of-CD19

Comparison of the safety profiles of CD19-targeting CAR T ... Despite similar CAR T-cell dynamics, patients with SLE experienced less severe adverse events after CAR T-cell therapy than those with B-NHL ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05535855

UCD19 CAR T Therapy in Adults With B-ALL and MRD ... This open-label, single arm Phase 1/1b trial aims to determine the safety and tolerability of anti-CD19 chimeric antigen receptor-expressing (CAR) T cells ...