CAR T-Cell Therapy for Lymphoma

Overseen By Emerging Medicine

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Disqualifiers: Uncontrolled infection, Hepatitis B/C, HIV, 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 retreatment using CTL019/CTL119, a type of CAR T-cell therapy, to evaluate its effectiveness for individuals with certain B-cell lymphomas that have recurred after a long remission. The goal is to determine if this treatment can benefit those with no other curative options and a limited prognosis with existing therapies. Suitable candidates have previously responded well to this therapy, have diffuse large B-cell or follicular lymphoma, and lack other curative treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that CTL019/CTL119, a type of CAR T-cell therapy, has produced varying safety results in past studies. One study found the treatment generally safe, with most side effects being mild. However, another study reported that all patients experienced cytokine release syndrome (CRS), a common side effect. This ranged from mild in about 40.6% of patients to severe in 50%, with fatal cases in 9.37% of patients.

While CAR T-cell therapy can be effective, discussing the potential risks and benefits with a healthcare provider is important. Ensure a clear understanding of what participating in a trial might involve. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CAR T-Cell Therapy, specifically CTL019/CTL119, is unique because it harnesses the body's own immune system to fight lymphoma. Unlike traditional treatments like chemotherapy and radiation that target cancer cells broadly, this therapy involves modifying a patient’s T-cells to specifically seek out and destroy lymphoma cells. Researchers are excited about this treatment because it offers a more personalized approach, potentially with fewer side effects, and might be effective in cases where standard treatments have failed. This innovative approach represents a significant shift toward more targeted and potentially more effective cancer therapies.

What evidence suggests that CTL019/CTL119 might be an effective treatment for lymphoma?

Research has shown that CTL019/CTL119, a type of CAR T-cell therapy, may help treat B-cell lymphomas. In one study, 64% of patients responded positively to the treatment. Another study found that 13 out of 19 patients responded well, with 11 achieving complete remission, meaning their cancer was no longer detectable. These results suggest that CTL019/CTL119 could be effective for people with certain difficult-to-treat lymphomas. Although more research is needed, these early findings are promising for those considering this treatment. Participants in this trial will receive retreatment with CTL019/CTL119 and follow the schedule of procedures. ^{1 6 7 8 9}

Who Is on the Research Team?

Stephen Schuster, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults with B-cell lymphomas who've had a good response to previous CAR T-cell therapy (CTL019/CTL119) lasting at least 6 months. They should have no other curative options and a limited prognosis. Key health requirements include normal liver function, decent heart function, and stable performance status.

Inclusion Criteria

I had a successful CAR T-cell treatment lasting at least 6 months.

Agree to contraceptive requirements outlined in Section 4.3

My lymphoma is CD19 positive.

Exclusion Criteria

I currently have an infection that is not under control.

I am HIV positive.

Any uncontrolled active medical disorder that would preclude participation as outlined

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Retreatment

Participants receive retreatment with CTL019/CTL119 chimeric antigen receptor (CAR) modified T cells

3 months

Follow-up

Participants are monitored for safety and effectiveness after retreatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• CTL019/CTL119

Trial Overview

The study tests the effects of reusing CTL019/CTL119 cells in patients whose B-cell lymphoma has relapsed late after initial successful treatment. It's for those who previously participated in UPCC13413/NCT02030834 and still have their manufactured product available.

How Is the Trial Designed?

Group I: Retreatment with CTL019/CTL119 Experimental Treatment 1 Intervention

All subjects will receive retreatment with CTL019/CTL119 and be followed per the schedule of procedures.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., et al.[2023]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

The study developed a CAR (CD4CAR) that enables CD8+ T cells to target and eliminate CD4+ T-cell lymphomas, showing effectiveness in both laboratory and patient-derived samples.

In mouse models of aggressive T-cell lymphoma, CD4CAR T cells not only suppressed tumor growth but also significantly extended survival, suggesting their potential as a new treatment option for patients with peripheral T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Pinz, K., Liu, H., Golightly, M., et al.[2018]

CAR T-cell therapy, particularly anti-CD19 CAR T cells, shows strong efficacy in treating resistant forms of B-cell lymphomas, achieving durable complete remissions lasting over 2 years in some patients with refractory diffuse large-B-cell lymphoma (DLBCL).

Despite their effectiveness, CAR T-cell therapies can lead to severe toxicities, such as cytokine-release syndrome and neurological issues, highlighting the need for careful management and ongoing research into safer CAR designs and treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. Brudno, JN., Kochenderfer, JN.[2022]

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

CAR T-cell therapy is a groundbreaking treatment for recurrent B-cell lymphomas and acute lymphoid leukemia, showing over 80% remission rates and faster responses compared to traditional therapies, with a treatment duration of just 2-3 weeks.

While CAR T-cell therapy can lead to significant side effects like cytokine release syndrome and neurotoxicity, understanding these potential adverse events and their timelines is crucial for optimizing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists. de Groot, PM., Arevalo, O., Shah, K., et al.[2022]

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5788566/

Chimeric Antigen Receptor T Cells in Refractory B-Cell ...

RESULTS. A total of 28 adult patients with lymphoma received CTL019 cells, and 18 of 28 had a response (64%; 95% confidence interval [CI], 44 to 81).

2.

ashpublications.org

ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025016778/546741/Comparative-real-world-outcomes-of-CD19-directed

Comparative real-world outcomes of CD19-directed CAR T ...

Between April 2016 and July 2024, 624 patients received CD19-targeted CAR T-cell therapies (344 axi-cel, 142 tisa-cel, and 138 liso-cel). At a ...

3.

novartis.com

novartis.com/us-en/news/media-releases/novartis-highlights-ctl019-data-showing-its-potential-treatment-specific-types-hard-treat-non-hodgkin-lymphoma

Novartis highlights CTL019 data showing its potential in ...

Thirteen of 19 evaluable patients responded to the therapy. Eleven achieved a complete response (CR) and two experienced a partial response (PR) to treatment1.

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)02375-5/fulltext

805MO Real-world efficacy and safety of tisagenlecleucel ...

The 12-month progression-free survival (PFS) and overall survival (OS) rates were 62.6% and 84.9%, respectively (both medians were not reached). Among the 106 ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497119311012

Chimeric Antigen Receptor Modified T Cells Directed ...

At the median follow-up 11.4 mo from CTL019 infusion, the proportion of pts progression-free is 77% (95%CI: 45-92%) and the median TTNT not yet reached compared ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40960310/

Long-term outcomes of CNCT19 chimeric antigen receptor ...

After a median follow-up of 54.0 months, the estimated 5-year progression-free survival and overall survival rates were 25.0% and 37.5%, ...

7.

nature.com

nature.com/articles/s41409-025-02629-8

Clinical outcomes of a new local CD19 CAR-T cell therapy ...

The overall safety profile of PP CAR-T therapy was favorable, with the majority of adverse events (AEs) being grade I–II in severity. In the B- ...

8.

ascopubs.org

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

Long-term outcomes of CAR-T cell therapy in DLBCL.

Safety profile: CRS occurred in 100% of patients, with severe cases (Grade 3–4) in 50% mild to moderate 40.6% and fatal CRS in 9.37%.

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7416618/

Efficacy and safety of second-generation CAR T-cell therapy ...

The present study conducted a meta-analysis that showed highly favorable outcomes [objective response rate (ORR): 69%; complete remission (CR): 49%] in B-cell ...