CAR T-Cell Therapy for Leukemia and Lymphoma

Overseen By Clelie Peck

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nationwide Children's Hospital

Disqualifiers: Neurologic toxicity, Untreated infection, Genetic syndrome, GVHD, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called anti-CD19 CAR T-cell therapy, a type of immunotherapy, for children and young adults with certain blood cancers—B cell acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma—that have returned or resisted other treatments. The trial examines the safety and effectiveness of this treatment. It seeks participants who have experienced cancer relapse after a bone marrow transplant or have not responded to traditional chemotherapy. The trial involves collecting cells from the patient, administering specific chemotherapy to prepare their body, and then infusing the modified cells back to combat the cancer. Participants will be monitored for up to a year after the infusion to assess the treatment’s effects. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy and CAR T-cell therapy, it's possible that some medications might need to be adjusted. It's best to discuss your current medications with the trial team.

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

Research shows that anti-CD19 CAR T-cell therapy can effectively treat certain blood cancers, such as B-cell lymphoma that has returned or resisted other treatments. This therapy modifies a patient's own immune cells to better locate and attack cancer cells.

Regarding safety, studies indicate that patients generally tolerate this therapy well. However, some may experience side effects ranging from mild to severe, including fever, tiredness, and low blood pressure. Severe reactions are less common but can occur.

This therapy remains in the early stages of testing, so researchers are still confirming its safety and effectiveness. While early results appear promising, potential risks remain under investigation. Patients considering trial participation should discuss possible side effects and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia and lymphoma, which often include chemotherapy and radiation, CAR T-cell therapy harnesses the power of the immune system by engineering a patient's own T-cells to target and destroy cancer cells. This treatment is unique because it uses a chimeric antigen receptor (CAR) to specifically recognize the CD19 protein found on the surface of cancer cells. Researchers are excited because this targeted approach has the potential for high precision in attacking cancer cells while sparing healthy ones, which could lead to fewer side effects and more effective outcomes. Additionally, this therapy represents a one-time treatment that might offer long-lasting remission, making it a promising alternative to ongoing conventional therapies.

What evidence suggests that this CAR T-Cell therapy is effective for leukemia and lymphoma?

Research shows that CD19-targeted CAR T-cell therapy, which participants in this trial will receive, has greatly improved outcomes for some blood cancers. Specifically, patients with B-cell non-Hodgkin lymphoma have benefited from this treatment. Studies have found that this therapy can lead to long-lasting remission. Young adults receiving CD19 CAR T-cell therapy have experienced similar success, regardless of the specific version used. While early results are promising, ongoing research aims to fully understand its potential and safety. ^{4 6 7 8 9}

Who Is on the Research Team?

Margaret Lamb, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults up to age 30 with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or non-Hodgkin lymphoma. Participants must have a certain level of heart, liver, kidney, and lung function, agree to use contraception if applicable, and not be pregnant. They can't join if they have HIV/AIDS, uncontrolled infections including hepatitis B/C, recent graft versus host disease after a transplant, any prior CD19 CAR T cell therapy or are part of another investigational study within the last month.

Inclusion Criteria

I was diagnosed with my condition before turning 31.

My child has B-Cell ALL that has not responded to treatment.

My parent or guardian has signed the consent form for me.

Exclusion Criteria

I have no major ongoing nerve-related issues except for controlled seizures or stable conditions.

I do not have active hepatitis B or C, nor any uncontrolled infections.

I am experiencing moderate to severe symptoms from a transplant reaction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Collection of autologous lymphocytes from the patient via apheresis

1 day

1 visit (in-person)

Lymphodepleting Chemotherapy

Administration of fludarabine and cyclophosphamide to prepare the body for CAR T cell infusion

4 days

Inpatient stay

CAR T Cell Infusion

Infusion of anti-CD19 CAR T cells after lymphodepleting chemotherapy

1 day

Inpatient stay

Immediate Post-Infusion Monitoring

Patients are monitored for toxicity including cytokine release syndrome, neurologic toxicity, and tumor lysis syndrome

7 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term Follow-up

Monitoring for potential long-term side effects of cell therapy

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CD19 specific Chimeric Antigen Receptor T Cell

Trial Overview The trial tests anti-CD19 CAR T cells made on-site for safety and effectiveness against specific blood cancers. It involves screening patients followed by chemotherapy to prepare their bodies before infusing these engineered immune cells. The process includes collecting patient's cells (leukapheresis), giving chemo drugs fludarabine/cyclophosphamide over four days then infusing the CAR T cells between day 2-14 post-chemo.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Leukopharesis: cells collected with a target of ≥1 x10\^9 TNC with ≥3% CD3+ cells. Lymphodepleting chemotherapy: 4 days of IV chemotherapy with fludarabine and cyclophosphamide. * Fludarabine 30 mg/m2/day IV x 4 days (days -6 through -3) * Cyclophosphamide 500 mg/m2/day IV x 2 days (days -6 and-5) anti-CD19 CAR T cells: * 0.3 - 1 x 10\^6 per kilogram for patients \<50 kg * Flat dose of 0.3 - 1 x 10\^8 for patients ≥50 kg The cell infusion will take place on day 0 (at least 2 days after completion of lymphodepleting chemotherapy). The patient will receive pre-medication with acetaminophen and diphenhydramine 30-60 minutes prior to the cell infusion.

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Published Research Related to This Trial

Chimeric antigen receptor (CAR) therapy, particularly targeting CD19, has shown significant efficacy in treating patients with chemorefractory B cell malignancies, leading to its potential regulatory approval as a cell-based immunotherapy.

While CAR therapy is effective, it is associated with toxicities such as cytokine release syndrome, neurotoxicity, and B cell aplasia, which require careful management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. Davila, ML., Sadelain, M.[2023]

CD19-targeted CAR-T cell therapy has shown high efficacy in treating relapsed/refractory B-cell malignancies, with recent trials demonstrating impressive initial results and durable responses.

Despite its effectiveness, CAR-T therapy faces significant challenges, including life-threatening side effects like cytokine release syndrome and neurotoxicity, highlighting the need for improved safety measures and further research into targeting other B-cell antigens and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials for chimeric antigen receptor T-cell therapy: lessons learned and future directions. Schroeder, BA., Jess, J., Sankaran, H., 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]

In a Phase I trial involving 43 pediatric and young adult patients with leukemia, initial treatment failures were linked to poor CAR T cell expansion and rapid loss of functional CAR T cells after infusion.

For patients who achieved remission, the durability of that remission was associated with higher levels of TNF-α-secreting CAR CD8+ T cells and sufficient CD19 antigen levels at the time of treatment, suggesting these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T cell product and disease attributes predict leukemia remission durability. Finney, OC., Brakke, HM., Rawlings-Rhea, S., et al.[2022]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

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]

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]

CAR T-cell therapy has shown remarkable success in treating B-cell acute lymphoblastic leukemia by targeting the CD19 marker, which is present on most B-cell tumors.

The therapy is being explored for other B-cell malignancies, including chronic lymphocytic leukemia and various types of lymphoma, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Pegram, HJ., Smith, EL., Rafiq, S., et al.[2018]

CD19CAR-T cell therapy is effective in treating relapsed and refractory B-lineage acute lymphoblastic leukemia, with four out of five patients achieving complete remission and minimal residual disease negativity.

The therapy can be safely administered with real-time monitoring of a 6-cytokine pattern, allowing for effective management of side effects like cytokine release syndrome and neurotoxicity using tocilizumab and steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. Shen, D., Song, H., Xu, X., et al.[2021]

CAR-T therapy has shown promising results in treating leukemia and lymphoma, offering potentially curative options for patients who previously had limited treatment choices, as highlighted in studies presented at the 61st annual meeting of the American Society of Hematology.

Recent advancements in CAR-T constructs aim to enhance treatment efficacy and durability while also improving strategies to manage toxicity, indicating a focus on both effectiveness and patient safety in the evolving field of cellular immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates in Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Lymphoma and Leukemia from the Annual Meeting of American Society of Hematology 2019. Bukhari, A., Siglin, J., Lutfi, F., et al.[2020]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10527363/

Outcomes of Chimeric Antigen Receptor (CAR) T-Cell ... Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have greatly improved the outcomes of many B-cell non-Hodgkin lymphomas ...

2. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... 2-targeted CAR has proven effective in treating gastrointestinal tumors in a study including 37 patients (NCT04196413), with an overall response ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723011314

Outcomes of CD19-Directed Chimeric Antigen Receptor T ... We analyzed and compared outcomes in patients with tCLL/SLL or tMZL and patients with DLBCL/tFL. The study included 134 patients who received a total of 136 CAR ...

4. ashpublications.org ashpublications.org/bloodadvances/article/9/11/2763/536292/Real-world-outcomes-for-young-adult-patients

Real-world outcomes for young adult patients receiving CD19 ... Key PointsReal-world efficacy among YAs receiving CD19 CAR T was comparable irrespective of CAR T construct.CRS and ICANS were observed more ...

5. bloodcancerunited.org bloodcancerunited.org/blood-cancer-care/adults/types-blood-cancer-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy

Chimeric antigen receptor (CAR) T-cell therapy Data from long-term outcome studies following CAR T-cell therapy indicates that CD19-targeted CAR T cells can induce prolonged remissions in patients with B- ...

6. 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 ...

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

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

8. 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 ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7003

A phase 1 study of KITE-363 anti-CD19/CD20 chimeric ... At 7.3 months median follow-up, ORR in CAR-naive pts at DL 3 was 87%; complete response (CR) rate was 78%. Among those, all 7 pts with LBCL who ...