CAR T-cell Therapy for Pediatric Leukemia & Lymphoma

Overseen By Vanessa Fabrizio, MD, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Disqualifiers: CNS leukemia, GvHD, severe infection, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called CAR T-cell therapy for children and young adults with certain blood cancers, specifically leukemia and lymphoma. The goal is to determine if these specially engineered cells can help patients who haven't responded to other treatments or have relapsed. The trial consists of two parts: the first tests different doses, and the second uses the best dose identified. This trial may suit those with specific types of B-cell leukemia or lymphoma who have relapsed or haven't responded well to other treatments. 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 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 using CAR-T cell therapy to target CD19 successfully treats certain types of non-Hodgkin lymphoma (NHL). This therapy employs a patient's own modified immune cells to attack cancer cells. Similar CAR-T therapies have already been approved and effectively used for other blood cancers.

These therapies are generally well-tolerated, though side effects can occur. Common side effects include fever and low blood pressure, typically resulting from the immune system's active fight against cancer. Serious side effects are possible but less common, and doctors closely monitor patients to manage them.

As this trial is in an early phase, safety remains a key focus. Early phase trials often aim to determine the safest dose. While this therapy is new for children with leukemia and lymphoma, its use in other conditions suggests a known safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells because this treatment offers a unique approach to tackling pediatric leukemia and lymphoma. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, this CAR T-cell therapy is engineered to specifically recognize and attack cancer cells expressing the CD19 protein. This precision reduces damage to healthy cells and can lead to fewer side effects. Moreover, this personalized treatment uses the patient's own T-cells, which are modified to enhance their cancer-fighting abilities, providing a potentially powerful and tailored immune response against the disease.

What evidence suggests that this treatment might be an effective treatment for pediatric leukemia and lymphoma?

Research has shown that CD19-targeted CAR T-cell therapy holds promise for treating blood cancers like leukemia and lymphoma. This therapy has proven especially beneficial for individuals with large B-cell lymphoma (LBCL) that has recurred or resisted other treatments, with several products already available. Studies have demonstrated that these therapies can provide long-lasting effectiveness, with positive outcomes persisting for several years. In this trial, the new therapy also targets the CD19 protein on cancer cells, which is crucial for its success. Early results indicate that this treatment can induce remission in some patients when other treatments have failed. The goal is to extend these benefits to more people, including children. ^{1 2 4 6 7}

Who Is on the Research Team?

Vanessa Fabrizio, MD

Principal Investigator

Children's Hospital Colorado

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 month to 25 years with B-cell Acute Lymphoid Leukemia or Non-Hodgkin's Lymphoma that has relapsed multiple times, failed standard treatments, or occurred after a bone marrow transplant. Participants must have CD19 expression and be able to perform daily activities at least half of the time.

Inclusion Criteria

Willingness to participate in long-term follow-up study

I can do most activities but need help with some.

Provision of signed and dated consent form from parent or guardian (patients <18), the patient themselves (>18), or legally authorized representative (patient >18 who lack decision-making capacity)

Exclusion Criteria

My organs are too weak for certain cancer treatments.

I have HIV or active Hepatitis B/C.

I have not had gene therapy or CAR-T cell treatment before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

First 3-21 subjects enrolled and treated with escalating doses of therapy until the RP2D is determined

Variable

Dose Expansion

22-40 additional subjects treated at the RP2D, including those treated within the phase 1 portion of the trial

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells

Trial Overview The study tests a new CAR-T cell therapy targeting CD19 on cancer cells in pediatric patients. It aims to provide quicker access to treatment for those who've had limited options before, including kids with B-cell NHL or those experiencing their first relapse.

How Is the Trial Designed?

Group I: Phase II: Dose Expansion Experimental Treatment 1 Intervention

Up to 18 additional subjects will be treated at the recommended Phase 2 dose (RP2D) to allow for 12 total subjects to be treated in each cohort, including those treated within the phase 1 portion.

Group II: Phase I: Dose Escalation Experimental Treatment 1 Intervention

First 4-18 subjects enrolled. Treated with escalating doses of therapy until the recommended phase 2 dose (RP2D) is determined.

CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells is already approved in United States, European Union for the following indications:

Approved in United States as CD19 CAR T-cell therapy for:

• Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (R/R B-ALL)
• Relapsed/Refractory Non-Hodgkin Lymphoma (R/R NHL)

Approved in European Union as CD19 CAR T-cell therapy for:

• Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (R/R B-ALL)
• Relapsed/Refractory Non-Hodgkin Lymphoma (R/R NHL)

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

CAR T-cell therapies, such as tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), are effective treatments for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T cells that target the CD19 antigen.

These therapies are classified as 'living drugs' because they involve the genetic engineering of a patient's own T cells, highlighting the importance of proper collection and manufacturing processes for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. Carnoy, S., Beaumont, JL., Kanouni, T., et al.[2021]

Chimeric antigen receptor (CAR) T-cell therapy targeting the CD19 antigen has shown high effectiveness in treating patients with relapsed or refractory B-cell malignancies, with several therapies like tisagenlecleucel already approved in Japan.

Research is ongoing for CAR T-cell therapies targeting other cancers, such as acute myeloid leukemia (AML) and multiple myeloma, indicating a broadening scope of CAR T-cell applications beyond just B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptor T-cell therapy for hematological malignancies]. Nakazawa, Y.[2019]

In the updated ZUMA-3 study with a median follow-up of 26.8 months, brexucabtagene autoleucel (KTE-X19) achieved a 71% complete remission rate in adults with relapsed or refractory B-precursor acute lymphoblastic leukemia, indicating its efficacy as a treatment option.

Patients treated with KTE-X19 had a median overall survival of 25.4 months, significantly longer than the 5.5 months observed in matched historical controls, demonstrating a meaningful survival benefit with manageable safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. Shah, BD., Ghobadi, A., Oluwole, OO., et al.[2023]

Tisagenlecleucel and axicabtagene ciloleucel are groundbreaking CAR-T cell therapies that have shown high effectiveness in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and certain types of B-cell non-Hodgkin lymphomas.

This review highlights the challenges faced by physicians in administering these therapies and discusses future directions for research and treatment in the field of immune and cellular therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Mohty, M., Gautier, J., Malard, F., et al.[2022]

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]

Axicabtagene ciloleucel and tisagenlecleucel are FDA-approved CAR T cell therapies specifically designed to target CD19 in patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma, marking a significant advancement in cellular immunotherapy.

Despite their transformative potential, there are ongoing concerns about the appropriate use and potential short- and long-term toxicities of these therapies, prompting expert consensus to guide clinicians in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Jain, T., Bar, M., Kansagra, AJ., et al.[2020]

The FDA has approved tisagenlecleucel, the first anti-CD19 CAR T-cell therapy, specifically for treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia (ALL).

CAR T-cell therapy, particularly with tisagenlecleucel, shows promise as a standard treatment option for patients with B-cell malignancies, although it has primarily been developed through small clinical studies and poses unique management challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. Thomas, X., Paubelle, E.[2019]

A survey of 41 experienced clinicians revealed that many do not consider a history of malignancy or prior treatments as contraindications for CAR T-cell therapy, indicating a broader eligibility for patients than previously thought.

There is significant variability in follow-up care models after CAR T therapy, with most clinicians recommending frequent hospital visits in the initial month, highlighting the need for standardized guidelines in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. Hayden, PJ., Sirait, T., Koster, L., et al.[2021]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

Tisagenlecleucel is the first FDA-approved CD19-targeted CAR T cell therapy specifically for pediatric patients with pre-B-cell acute lymphoblastic leukemia (B-ALL), showing excellent responses in a multicenter phase II trial for those with highly refractory disease.

While CAR T cell therapy can lead to durable remissions in many patients, close monitoring for unique toxicities such as cytokine release syndrome and neurotoxicity is essential after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia. Pacenta, HL., Laetsch, TW., John, S.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11305028/

Approved CAR-T therapies have reproducible efficacy and ... Anti-CD19 CAR-T cell therapy has proven to be a valuable asset in the treatment of R/R LBCL and there are currently three commercial products ...

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

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/18/3834/764532/Facts-and-Hopes-CAR-T-Cell-Therapy-and-Immune

CAR T-Cell Therapy and Immune Contexture in Non-Hodgkin ... This review focuses on biomarkers associated with CAR T-cell therapy in mature B-cell non-Hodgkin lymphoma malignancies, underscoring the importance of ...

4. multiplemyelomahub.com multiplemyelomahub.com/medical-information/long-term-outcomes-following-car-t-cell-therapy-in-b-cell-malignancies

Long-term outcomes following CAR T-cell therapy in B- ... Data from 12 studies at a median follow-up of 1-year (range, 1–4.8 years) outline the long-term efficacy of CD19-targeted CAR T-cell therapies in B-ALL.

5. mcgs.bcbsfl.com mcgs.bcbsfl.com/MCG?mcgId=09-J3000-94&pv=false

Subject: Chimeric Antigen Receptor (CAR) T-Cell Therapies Axicabtagene ciloleucel (Yescarta) is a CD19-directed, genetically-modified autologous T cell immunotherapy that was first approved by the U.S. ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0037196324000891

The Development of CAR T-Cell Therapy in the Earlier ... Targeting CD19 with CAR-T cell therapy has been very successful in B-cell NHL with 4 CAR-T cell products available to date and with various indications: ...

7. chi.scholasticahq.com chi.scholasticahq.com/article/124277-overview-of-approved-car-t-products-and-utility-in-clinical-practice

Overview of approved CAR-T products and utility in clinical ... Below, we review the currently commercially available CAR T-cell products and their indications as of 2023.