CAR-T Therapy for Acute Lymphoblastic Leukemia

Overseen By James Rolland

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

Trial Summary

What is the purpose of this trial?

This is a Phase 2 Study is to determine the efficacy and safety rate of B-Cell Acute Lymphoblastic Leukemia (B-ALL) participants in remission with minimal residual disease (MRD) after KTE-X19 CAR T-cell 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.

What data supports the effectiveness of the treatment KTE-X19 (Tecartus, Brexucabtagene autoleucel) for acute lymphoblastic leukemia?

The effectiveness of KTE-X19 for treating acute lymphoblastic leukemia is supported by the ZUMA-3 trial, where 52% of patients achieved complete remission within 3 months. This treatment has also shown promise in other conditions like mantle cell lymphoma, indicating its potential effectiveness. ^{1 2 3 4 5}

Is CAR-T therapy (KTE-X19, Tecartus, Brexucabtagene autoleucel) safe for humans?

Brexucabtagene autoleucel (KTE-X19) has been approved for treating certain types of leukemia and lymphoma, but it can have serious side effects. In studies, serious reactions occurred in 79% of patients, with 5% experiencing fatal reactions like brain swelling and infections. Common side effects include cytokine release syndrome (a severe immune reaction) and neurological issues, which led to a special safety monitoring program. ^{1 2 3 4 5}

How is the treatment KTE-X19 (Tecartus) different from other treatments for acute lymphoblastic leukemia?

KTE-X19 (Tecartus) is unique because it is a CAR T-cell therapy, which means it uses the patient's own immune cells that are genetically modified to target and destroy cancer cells. This treatment is specifically approved for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, offering a new option for patients who have not responded to other treatments. ^{1 2 3 6 7}

Research Team

Bijal Shah, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

My leukemia is CD19 positive.

I am fully active or can carry out light work.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. [2022]

4. United States 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. [2023]

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. [2019]

7. England 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). [2023]