Brexucabtagene Autoleucel + Dasatinib for Acute Lymphoblastic Leukemia

Overseen By Alyssa M Kanega

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Corticosteroids, TKIs, others

Disqualifiers: CNS disorders, Cardiac disease, 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

Duration: 1 month

20 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess the feasibility of oral dasatinib pulses (3 consecutive days per week) during the first month following infusion of brexucabtagene autoleucel (Tecartus) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had salvage chemotherapy, corticosteroid therapy, or certain other treatments shortly before enrolling. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Brexucabtagene Autoleucel (KTE-X19) for Acute Lymphoblastic Leukemia?

Brexucabtagene autoleucel (KTE-X19) has shown effectiveness in treating adults with relapsed or refractory B-cell acute lymphoblastic leukemia, with a complete remission rate of 73% and a median overall survival of 25.4 months, based on the ZUMA-3 trial results. ^{1 2 3 4 5}

Is Brexucabtagene Autoleucel (Tecartus) safe for humans?

Brexucabtagene Autoleucel (also known as Tecartus or KTE-X19) has been associated with serious side effects in clinical trials, including cytokine release syndrome (a severe immune reaction) in 92% of patients and neurologic toxicities in 87% of patients, with some cases being severe. Serious adverse reactions occurred in 79% of patients, and fatal reactions occurred in 5%, including cerebral edema (brain swelling) and infections. ^{1 2 5 6 7}

What makes the treatment Brexucabtagene Autoleucel unique for acute lymphoblastic leukemia?

Brexucabtagene autoleucel is a unique treatment because it is a CAR T-cell therapy that specifically targets the CD19 protein on cancer cells, offering a personalized approach by using the patient's own modified immune cells to fight the leukemia. It is particularly novel as it was the first of its kind approved for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, providing a new option for patients who have not responded to other treatments. ^{1 2 3 4 5}

Research Team

Lori Muffly, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults with B-cell acute lymphoblastic leukemia that's come back or hasn't responded to treatment can join. They need good liver, kidney, heart, and lung function; a normal heartbeat; not pregnant; willing to use birth control for six months after treatment; and no severe active infections or recent serious heart issues.

Inclusion Criteria

My lung function is good and my bilirubin levels are normal or near normal.

My kidneys are working well.

My heart is strong and works well.

Exclusion Criteria

I have brain involvement with changes in my neurological condition.

I have an autoimmune disease and have been on immunosuppressive drugs in the past year.

I have not taken corticosteroids in the week before joining.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brexucabtagene autoleucel infusion followed by oral dasatinib pulses (3 consecutive days per week) during the first month

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

2 years

Treatment Details

Interventions

• Brexucabtagene Autoleucel
• Dasatinib

Trial Overview The trial tests if taking dasatinib orally for three days a week after getting brexucabtagene autoleucel (Tecartus) is doable in adults with relapsed/refractory B-cell acute lymphoblastic leukemia.

Participant Groups

Group I: Dasatinib Experimental Treatment 1 Intervention

Oral dasatinib 100mg

Brexucabtagene Autoleucel is already approved in European Union, United States for the following indications:

Approved in European Union as Tecartus for:

• Mantle cell lymphoma (MCL)
• Acute lymphoblastic leukemia (ALL)

Approved in United States as Tecartus for:

• Mantle cell lymphoma (MCL)
• Acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Kite Pharma

Collaborator

Trials

2

Recruited

40+

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 (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 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]

Tisagenlecleucel, a CAR-T cell therapy, shows high overall remission rates of 69% to 93% in patients with relapsed/refractory B-cell acute lymphoblastic leukemia, with durable 12-month relapse-free survival rates of 55% to 59%.

However, the treatment is associated with significant risks, including potentially life-threatening cytokine release syndrome in 77% to 100% of patients and neurotoxicity in 31% to 45%, highlighting the need for careful patient selection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations. Halford, Z., Anderson, MK., Bennett, LL., et al.[2021]

Brexucabtagene autoleucel (brexu-cel) demonstrated a high overall complete remission rate of 73% and a median overall survival of 25.4 months in adults with relapsed or refractory B-cell acute lymphoblastic leukemia, based on a study of 78 patients with a median follow-up of 29.7 months.

The therapy was effective across various prior treatment subgroups, with high remission rates regardless of previous therapies, indicating its potential as a robust treatment option for patients with R/R B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3. Shah, BD., Cassaday, RD., Park, JH., 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 (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]

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

Matching-Adjusted Indirect Comparisons of Brexucabtagene Autoleucel with Alternative Standard Therapies for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients. [2023]

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

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

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

Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3. [2023]

6. 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]

7. 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]