Brexucabtagene Autoleucel + Dasatinib for Acute Lymphoblastic Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Lori Muffly, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Stanford University

Must not be taking: Corticosteroids, TKIs, others

Disqualifiers: CNS disorders, Cardiac disease, others

No Placebo Group

Approved in 2 Jurisdictions

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stanford University Palo Alto, CA

Who Is Running the Clinical Trial?

Stanford University Lead Sponsor

Kite Pharma Collaborator

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] Brexucabtagene autoleucel (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 leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care.

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] Brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, is approved for relapsed/refractory B-cell precursor acute lymphoblastic leukemia in adults aged 18+/26+ years in the US/European Union (EU), based on efficacy results from the single-arm ZUMA-3 trial. This study aimed to estimate the relative treatment effects of brexu-cel versus inotuzumab ozogamicin (InO), blinatumomab (blina), and chemotherapies using unanchored matching-adjusted indirect comparison (MAIC) methods.

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

Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. [2022] In October 2021, brexucabtagene autoleucel became the first anti-CD19 chimeric antigen receptor T-cell product to receive approval from the Food and Drug Administration to treat adults with relapsed and refractory B-cell acute lymphoblastic leukemia. The approval is based on results from the Zuma-3 trial and significantly widens treatment options for this patient population. In this article, we review outcomes from this study and its implications.

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

Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations. [2021] To evaluate the current literature for tisagenlecleucel in the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL).

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] Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.

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] In October 2021, the FDA approved brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Approval was based on the phase II portion of ZUMA-3, a single-arm, open-label, multicenter trial that evaluated a single infusion of brexu-cel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine, in this population. Efficacy was established on the basis of complete remission (CR) within 3 months after infusion and the duration of CR (DOCR). Among 54 patients in the efficacy analysis population, the CR rate was 52% (95% CI: 38, 66) with a median time-to-response of 56 days. With a median follow-up for responders of 7.1 months, the median DOCR was not reached. For all leukapheresed patients in the phase II portion of this trial (n = 71), the CR rate was 41% (95% CI: 29, 53). Among the 78 patients treated with the approved dose of brexu-cel, serious adverse reactions occurred in 79% and fatal adverse reactions occurred in 5% and included cerebral edema and infections. Cytokine release syndrome occurred in 92% (grade ≥3, 26%) and neurologic toxicities occurred in 87% (grade ≥3, 35%), leading to implementation of a risk evaluation and mitigation strategy (REMS). Postmarketing study with 15 years of follow-up will further evaluate long-term safety in adult patients with relapsed or refractory B-ALL.

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] Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in the pivotal ZUMA-2 study of KTE-X19 in relapsed/refractory MCL are reported, including for subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics.