CAR-T Therapy for Acute Lymphoblastic Leukemia

Overseen By Connor Tate

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Infections, Cardiac disease, CNS disorders, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment called KTE-X19, a type of CAR-T therapy, for individuals with B-cell acute lymphoblastic leukemia (B-ALL) who are in remission but still have traces of disease. The trial aims to understand the safety and effectiveness of this treatment, which uses modified immune cells to target and kill cancer cells. This study suits adults diagnosed with B-ALL who have completed initial chemotherapy and are in remission with minimal residual disease. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in cancer 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, you must avoid corticosteroid therapy at a dose greater than 5 mg/day of prednisone (a type of steroid) or equivalent for 7 days before joining the trial.

Is there any evidence suggesting that KTE-X19 CAR T-cell therapy is likely to be safe for humans?

Research has shown that KTE-X19, also known as Tecartus, has been tested in patients with certain types of acute lymphoblastic leukemia, a cancer affecting the blood and bone marrow. Studies have found that while this treatment can be effective, some side effects require consideration.

Common side effects include low blood cell counts, leading to conditions like low white blood cells (neutropenia and leukopenia) and low platelets (thrombocytopenia). These conditions can increase the risk of infections and bleeding. Almost all patients in past studies experienced these side effects, with severe cases being quite common.

Despite these risks, the FDA has approved KTE-X19 for certain leukemia treatments, indicating that its benefits can outweigh the risks in specific situations. However, potential participants should consult their doctors to fully understand what joining a trial might mean for their health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute lymphoblastic leukemia, which typically involve chemotherapy or stem cell transplants, KTE-X19 is a form of CAR-T cell therapy that uses a patient's own immune cells to fight cancer. This treatment is unique because it modifies these cells to better recognize and attack leukemia cells, potentially offering a more personalized and precise approach. Researchers are excited about KTE-X19 because it targets specific cancer cells, which might lead to fewer side effects and improved outcomes compared to traditional methods. By harnessing the power of the immune system itself, this therapy could revolutionize how we treat leukemia, offering hope for patients who might not respond well to existing treatments.

What evidence suggests that KTE-X19 might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that KTE-X19, also known as Tecartus, yields promising results for treating B-cell acute lymphoblastic leukemia (B-ALL). Studies have demonstrated high response rates in patients whose cancer returned or did not respond to previous treatments, indicating that the cancer reacted well to this new treatment. Specifically, one study found that many patients went into remission, meaning their cancer became undetectable. Long-term follow-ups revealed that the treatment's benefits persisted over time. In this trial, participants will receive KTE-X19 as autologous CAR T-cell immunotherapy. Overall, these findings suggest that KTE-X19 could be an effective option for B-ALL patients in remission with very low levels of remaining cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Bijal Shah, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with B-cell acute lymphoblastic leukemia (B-ALL) that's CD19 positive can join. They must be in remission but still have minimal residual disease after induction chemotherapy. Participants need to be generally healthy, able to follow the trial schedule, and willing to use birth control during and for 6 months after the study.

Inclusion Criteria

My leukemia is CD19 positive.

Be willing and able to provide written informed consent/assent for the trial

I am fully active or can carry out light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy prior to CAR T-cell infusion

1 day

Treatment

Participants receive KTE-X19 CAR T-cell therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• KTE-X19

Trial Overview The trial is testing KTE-X19 CAR T-cell therapy's effectiveness and safety in treating B-ALL patients who are in remission but have some remaining cancer cells detectable at very low levels.

How Is the Trial Designed?

Group I: Autologous CAR T-cell immunotherapy Experimental Treatment 1 Intervention

Tecartus will be delivered at a target dose of 1x106 cells / kg. For those \>100 kg, a flat dose of 1 x108 cells will be used. Tecartus will be administered on day 0, following 1 day of rest from conditioning chemotherapy.

KTE-X19 is already approved in United States, European Union for the following indications:

Approved in United States as Tecartus for:

• Mantle Cell Lymphoma
• B-cell precursor Acute Lymphoblastic Leukemia

Approved in European Union as Tecartus for:

• Mantle Cell Lymphoma
• B-cell precursor Acute Lymphoblastic Leukemia

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Kite, A Gilead Company

Industry Sponsor

Trials

45

Recruited

4,300+

Published Research Related to This Trial

Brexucabtagene autoleucel is the first FDA-approved CAR T-cell therapy targeting CD19 for adults with relapsed and refractory B-cell acute lymphoblastic leukemia, marking a significant advancement in treatment options.

The approval was based on the outcomes of the Zuma-3 trial, which demonstrated the efficacy of this therapy in improving patient outcomes in a challenging-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. Frey, NV.[2022]

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]

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]

Tisagenlecleucel (KYMRIAH) is the first FDA-approved CAR-T therapy for children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia, marking a significant advancement in personalized cancer immunotherapy.

A global task force has been established to address challenges related to the implementation, safe delivery, and long-term monitoring of CAR-T therapy, providing guidance for hematologists and transplant physicians in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Kansagra, AJ., Frey, NV., Bar, M., et al.[2023]

Brexucabtagene autoleucel (KTE-X19) CAR T-cell therapy showed a remarkable 91% objective response rate and 68% complete response rate in 68 patients with relapsed/refractory mantle cell lymphoma after a median follow-up of 35.6 months, indicating its efficacy in this challenging patient population.

The therapy demonstrated durable long-term responses with manageable safety, as late-onset toxicities were infrequent, occurring in only 3% of patients, suggesting that KTE-X19 is a safe and effective treatment option even for those with high-risk characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Wang, M., Munoz, J., Goy, A., et al.[2023]

Brexucabtagene autoleucel (brexu-cel) is an FDA-approved CAR T-cell therapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL), showing a complete remission (CR) rate of 52% within 3 months after treatment in a study of 54 patients.

While brexu-cel demonstrates significant efficacy, it is associated with serious adverse reactions in 79% of patients, including severe cytokine release syndrome (92%) and neurological toxicities (87%), necessitating a risk evaluation and mitigation strategy (REMS) for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Bouchkouj, N., Lin, X., Wang, X., et al.[2022]

Brexucabtagene autoleucel (brexu-cel) significantly improves overall survival (OS) and event-free survival (EFS) compared to blinatumomab and standard chemotherapy, with hazard ratios indicating a strong treatment effect in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

In comparison to inotuzumab ozogamicin, brexu-cel also shows improved OS, while the EFS difference is not statistically significant, suggesting brexu-cel may be a more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparisons of Brexucabtagene Autoleucel with Alternative Standard Therapies for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients. Shah, B., Chen, JMH., Wu, JJ., et al.[2023]

Citations

1. tecartushcp.com tecartushcp.com/car-t-cell-therapy/acute-lymphoblastic-leukemia/response

TECARTUS® Efficacy Response Data for R/R B-cell ALL KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/16/4081/537144/Outcomes-of-brexucabtagene-autoleucel-in-patients

Outcomes of brexucabtagene autoleucel in patients with ... Outcomes of brexucabtagene autoleucel in patients with relapsed/refractory acute lymphoblastic leukemia with CNS involvement Open Access.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9734710/

Two-year follow-up of KTE-X19 in patients with relapsed or ... KTE-X19 is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic ...

4. nature.com nature.com/articles/s41375-025-02532-7

Three-year analysis of adult patients with relapsed or ... Three-year analysis of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02614066

NCT02614066 | A Study Evaluating the Safety and Efficacy ... The primary objectives of this study are to determine the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in adult participants with relapsed/ ...

6. tecartushcp.com tecartushcp.com/car-t-cell-therapy/acute-lymphoblastic-leukemia/safety-profile

TECARTUS® Safety Profile & Adverse Reactions TECARTUS® safety profile and adverse reactions in patients with R/R B-cell precursor acute lymphoblastic leukemia. See Important Safety Information.

7. fda.gov fda.gov/media/140409/download

Package Insert and Medication Guide - TECARTUS What is TECARTUS? TECARTUS is a treatment for adults with mantle cell lymphoma or acute lymphoblastic leukemia. It is used following disease progression ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/tecartus-epar-product-information_en.pdf

Tecartus, INN-brexucabtagene autoleucel - EMA The most common Grade 3 or higher haematological adverse reactions included neutropenia (99%), leukopenia (98%), lymphopenia (96%), thrombocytopenia (65%) and ...

9. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/523/531551/Efficacy-and-Safety-of-Brexucabtagene-Autoleucel

Efficacy and Safety of Brexucabtagene Autoleucel for ... Efficacy and safety of Brexucabtagene autoleucel for relapsed/refractory B-cell acute lymphoblastic leukemia in patients aged 60 and above.