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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for adults with a challenging form of blood cancer called B-cell acute lymphoblastic leukemia. The researchers aim to determine if adding dasatinib, taken orally for part of the week, can effectively complement brexucabtagene autoleucel (a type of CAR T-cell therapy). This trial seeks participants whose leukemia has returned or has not responded to previous treatments. Those who cannot join include individuals with prior issues with dasatinib or certain health conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dasatinib, one of the treatments in this trial, is generally well-tolerated. In a study with older patients who had a specific type of leukemia, researchers found dasatinib combined with mild chemotherapy to be manageable. Another study showed that 82% of patients were still alive after four years of taking dasatinib daily. However, some patients did experience serious side effects, such as infections.

Brexucabtagene autoleucel, also known as Tecartus, is another treatment in this trial. The FDA has already approved it for certain blood cancers. This approval suggests some level of safety, but each person may react differently. Like any treatment, there are potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Brexucabtagene Autoleucel combined with Dasatinib for Acute Lymphoblastic Leukemia because it represents a novel approach to targeting cancer cells. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Brexucabtagene Autoleucel is a type of CAR-T cell therapy that specifically modifies a patient's own immune cells to recognize and attack leukemia cells. This targeted mechanism could lead to more effective and less harmful treatment outcomes. Additionally, combining it with Dasatinib, an oral tyrosine kinase inhibitor, may enhance its effectiveness by further inhibiting the growth of cancer cells. This combination has the potential to revolutionize treatment by providing a more precise and personalized therapy option.

What evidence suggests that Brexucabtagene Autoleucel + Dasatinib could be effective for acute lymphoblastic leukemia?

This trial will evaluate the effectiveness of combining dasatinib with CAR T-cell therapy, specifically brexucabtagene autoleucel, for treating certain types of acute lymphoblastic leukemia (ALL), particularly when the leukemia has the Philadelphia chromosome (Ph+). Research has shown that this combination leads to high rates of complete molecular remission, making the disease undetectable at a very detailed level. Studies indicate that adding dasatinib to other treatments can result in long-term remissions and improved survival rates. Although more research is needed to confirm these benefits for everyone, early results are promising for its effectiveness in combating this type of leukemia. ^{6 7 8 9 10}

Who Is on the Research Team?

Lori Muffly, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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) 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]

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]

Citations

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SPRYCEL® (dasatinib) Efficacy - Newly Diagnosed Patients SPRYCEL patients achieved higher & faster cCCyR* and MMR† rates at Years 1 and 5 vs imatinib · Fatal adverse reactions occurred in 3 patients (4%), all of which ...

2. onclive.com onclive.com/view/dasatinib-plus-car-t-cell-therapy-shows-efficacy-in-ph-acute-lymphoblastic-leukemia

Dasatinib Plus CAR T-Cell Therapy Shows Efficacy in Ph+ ... Dasatinib plus CAR T cells led to high CMR and LFS rates with a good safety profile in Ph-positive acute lymphoblastic leukemia.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4081177/

First report of phase 2 study of dasatinib with hyper-CVAD for ... The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph + ALL.

4. news.bms.com news.bms.com/news/details/2017/Sprycel-dasatinib-Added-to-Standard-Chemotherapy-Demonstrates-Three-Year-Survival-Benefit-in-Pediatric-Patients-with-Newly-Diagnosed-Philadelphia-Chromosome-Positive-Acute-Lymphoblastic-Leukemia/default.aspx

Sprycel (dasatinib) Added to Standard Chemotherapy ... Showed event-free and overall survival rates of 65.5% and 91.5%, respectively 14.2% of patients treated with Sprycel induction therapy ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01075

Long-Term Results of the Dasatinib-Blinatumomab ... The initial report showed 60% of molecular responses (52% by intention to treat) at the primary end point (after two cycles of blinatumomab) and ...

6. sprycel-hcp.com sprycel-hcp.com/safety-newly-diagnosed

SPRYCEL® (dasatinib) Safety Profile - Newly Diagnosed ... Fatal adverse reactions occurred in 3 patients (4%), all of which were due to infections; Eight patients (10%) experienced adverse reactions leading to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5085255/

Dasatinib and low-intensity chemotherapy in elderly patients ... In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph+ ALL.

8. news.bms.com news.bms.com/news/details/2010/Four-Year-Follow-Up-Data-for-SPRYCEL-dasatinib-Demonstrate-82-Percent-Overall-Survival-in-Patients-with-Chronic-Myeloid-Leukemia-Who-Failed-Gleevec1/default.aspx

Four-Year Follow-Up Data for SPRYCEL® (dasatinib) ... At four years, for all patients administered SPRYCEL 100 mg once daily, overall survival was 82% (95% CI: 76%-88%) and progression-free survival was 66% (95% CI ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8027101/

Dasatinib in the Management of Pediatric Patients With ... Dasatinib plus chemotherapy showed good tolerability and outcomes similar to imatinib in COG AALL0031 (5-year OS 86% ± 5% overall, 87% ± 5% for ...

10. academic.oup.com academic.oup.com/jjco/advance-article/doi/10.1093/jjco/hyaf154/8271051

Safety profiles of dasatinib in pediatric patients: a real-world ... This study demonstrates key adverse events associated with dasatinib in pediatric patients and emphasizes the importance of enhanced ...