Axicabtagene Ciloleucel for Large B-Cell Lymphoma

(ZUMA-24 Trial)

Not currently recruiting at 16 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kite, A Gilead Company

Must be taking: Anti-CD20, Anthracycline

Must not be taking: IV antimicrobials

Disqualifiers: Stem cell transplant, CNS lymphoma, 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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of axicabtagene ciloleucel, a specialized cell therapy, for individuals with large B-cell lymphoma that has returned or resisted previous treatments. Participants will receive a combination of chemotherapy and this unique cell therapy in an outpatient setting. Suitable candidates have relapsed or hard-to-treat large B-cell lymphoma, have previously tried specific treatments, and are open to outpatient care and follow-up. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that axicabtagene ciloleucel has been thoroughly studied in patients with large B-cell lymphoma, including those whose cancer returned or didn't respond to other treatments. In past studies, this treatment consistently showed safe results across different patient groups. Most people tolerated it well, although some experienced side effects. These often included fever and low blood cell counts, common with treatments affecting the immune system. Standard medical care usually managed these side effects effectively.

The FDA has already approved axicabtagene ciloleucel for certain uses, indicating rigorous testing to ensure safety for specific situations. While every new trial aims to gather more safety data, existing evidence provides a solid understanding of how people might respond to the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Axicabtagene ciloleucel is unique because it uses chimeric antigen receptor (CAR) T-cell therapy to target large B-cell lymphoma. Unlike standard treatments, which often rely on chemotherapy and radiation, this therapy involves modifying a patient's own T cells to better recognize and attack cancer cells. This personalized approach has the potential to be more effective and offer longer-lasting remission for patients, making it a groundbreaking option in the fight against this type of lymphoma. Researchers are excited about its ability to specifically target cancer cells while sparing healthy ones, which could lead to fewer side effects and improved outcomes.

What evidence suggests that axicabtagene ciloleucel could be effective for large B-cell lymphoma?

Research shows that axicabtagene ciloleucel, which participants in this trial will receive, can effectively treat large B-cell lymphoma, especially in patients whose cancer has returned or not responded to other treatments. Studies have found that this treatment can significantly extend patients' lives compared to standard treatments. In real-world settings, patients receiving axicabtagene ciloleucel have experienced similar results, regardless of race or ethnicity. Although some patients may still see disease progression, the treatment has shown promise in extending patients' lives. ^{1 4 6 7 8}

Who Is on the Research Team?

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory large B-cell lymphoma who have had prior treatments including an anti-CD20 monoclonal antibody and chemotherapy. They must have at least one measurable lesion, be in good physical condition (ECOG status of 0 or 1), and agree to outpatient treatment. Excluded are those with a history of stem cell transplant, previous CAR T-cell therapy, CNS involvement by lymphoma, more than one line of LBCL therapy, or uncontrolled infections.

Inclusion Criteria

At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma

I've been treated with both an Anti-CD20 drug and anthracycline-based chemotherapy.

I have a specific type of advanced lymphoma and have undergone at least one treatment.

Exclusion Criteria

I have had a stem cell transplant using my own or donor cells.

I have or had cancer cells in my brain or spinal fluid.

I have had CAR-T cell therapy or similar treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine over 3 days

1 week

3 visits (in-person)

Treatment

Participants receive axicabtagene ciloleucel infusion following prophylactic corticosteroid treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Follow-up

Participants who complete at minimum 24 months follow-up will transition to a separate long-term follow-up study

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Axicabtagene Ciloleucel
• Cyclophosphamide
• Dexamethasone
• Fludarabine

Trial Overview The study tests axicabtagene ciloleucel given alongside steroids like dexamethasone in patients with large B-cell lymphoma that has come back after treatment or hasn't responded to it. The aim is to see how well the drug works when administered outside the hospital setting.

How Is the Trial Designed?

Group I: Axicabtagene Ciloleucel Experimental Treatment 4 Interventions

Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m\^2/day and fludarabine 30 mg/m\^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2. Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10\^6 cells/kg.

Axicabtagene Ciloleucel is already approved in United States, European Union for the following indications:

Approved in United States as Yescarta for:

• Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in European Union as Yescarta for:

• Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy
• Relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after three or more lines of systemic therapy

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Published Research Related to This Trial

Axicabtagene ciloleucel and tisagenlecleucel are effective CAR T-cell therapies targeting CD19 for treating B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma, but they can lead to serious complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

ICANS can occur alongside CRS and may affect the central nervous system due to elevated cytokine levels, but there is currently no consensus on the best management strategies for this condition, highlighting the need for improved identification and treatment protocols in intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies. Rivera, AM., May, S., Lei, M., et al.[2021]

In a study of 122 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed aggressive B-cell non-Hodgkin lymphoma, the overall response rate was 70% and the complete response rate was 50%, indicating strong efficacy even in a post-commercial setting with relaxed eligibility criteria.

Patients eligible for the original ZUMA-1 trial had significantly better outcomes, including higher complete response rates (63% vs. 42%) and longer duration of response, progression-free survival, and overall survival, while the rates of severe side effects like cytokine release syndrome and neurotoxicity were consistent with those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Jacobson, CA., Hunter, BD., Redd, R., et al.[2022]

Axicabtagene ciloleucel (Yescarta) is an approved second-line treatment for patients with large B-cell lymphoma who do not respond to or relapse within 12 months of initial chemoimmunotherapy.

Patient identity confirmation and premedication to reduce hypersensitivity reactions are essential steps in the administration of this autologous infusion therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Second-Line Treatment for B-Cell Lymphoma. Aschenbrenner, DS.[2022]

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.

While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. Halford, Z., Anderson, MK., Bennett, LL.[2021]

In two large randomized trials, adding intravenous paclitaxel to standard doxorubicin-cyclophosphamide (AC) therapy significantly improved disease-free survival at 5 years for women with early breast cancer, with one trial also showing improved overall survival.

While paclitaxel demonstrated efficacy in neoadjuvant therapy by increasing response rates and eligibility for breast-conserving surgery, it was associated with notable grade 3-4 adverse events, primarily hematological issues like neutropenia and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer. Simpson, D., Plosker, GL.[2018]

Axicabtagene ciloleucel and brexucabtagene autoleucel are effective anti-CD19 T-cell therapies that have shown high response rates in patients with relapsed and refractory B-cell malignancies, leading to FDA approvals for specific types of lymphoma.

Despite their effectiveness, these therapies can cause significant toxicities, such as cytokine release syndrome and neurologic issues, which necessitate careful management and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. Reagan, PM., Friedberg, JW.[2021]

The interim analysis of the phase 2 ZUMA-5 study showed that axicabtagene ciloleucel (axicel; Yescarta) provided significant and durable clinical benefits for patients with relapsed or refractory indolent non-Hodgkin lymphoma, indicating its efficacy in this patient population.

The treatment demonstrated a high overall response rate (ORR) and complete response (CR) rate, while maintaining a manageable safety profile, suggesting it is a viable option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim Phase 2 ZUMA-5 Results Show Promise for Axi-Cel in R/R iNHL. Slater, H.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8555382/

Outcomes of patients with large B-cell lymphoma ... However, the majority of axi-cel–treated patients will ultimately experience disease progression. Only limited data exist on patients with progressive disease ( ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301665

Survival with Axicabtagene Ciloleucel in Large B-Cell ... Axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than ...

3. ashpublications.org ashpublications.org/blood/article/143/26/2722/515777/Real-world-and-clinical-trial-outcomes-in-large-B

Real-world and clinical trial outcomes in large B-cell ... Overall survival and most safety outcomes with axi-cel were consistent across race/ethnicity in relapsed/refractory large B-cell lymphoma.

4. yescartahcp.com yescartahcp.com/large-b-cell-lymphoma/real-world-evidence

Real World Evidence | YESCARTA® (axicabtagene ciloleucel) Data were collected retrospectively from 298 patients with R/R LBCL who underwent leukapheresis at 17 US institutions as of September 30, 2018, with the intent ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03391466

NCT03391466 | Study of Effectiveness of Axicabtagene ... The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6990602/

Safety and efficacy of axicabtagene ciloleucel in refractory ... We provide an overview of axi-cel therapy, including efficacy and safety data, along with a practical discussion of current treatment considerations.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02348216

NCT02348216 | Study Evaluating the Safety and Efficacy of ... A Comparison of Two-Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients With Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38635762/

Real-world and clinical trial outcomes in large B-cell ... - PubMed Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings.