Axicabtagene Ciloleucel for Large B-Cell Lymphoma

(ZUMA-24 Trial)

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the study drug, axicabtagene ciloleucel, in participants with relapsed or refractory large B-cell lymphoma (LBCL) in the outpatient setting.

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.

What data supports the effectiveness of the treatment Axicabtagene Ciloleucel for Large B-Cell Lymphoma?

Research shows that Axicabtagene Ciloleucel (Yescarta) is effective for patients with relapsed or refractory large B-cell lymphoma, with significant and durable clinical benefits observed in clinical trials. It has been approved by the FDA for this condition due to its high response rates, although it can have serious side effects that need careful management. ^{1 2 3 4 5}

What safety data exists for Axicabtagene Ciloleucel (Yescarta) in humans?

Axicabtagene ciloleucel, a CAR T-cell therapy, can cause cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which are complications that affect the immune and nervous systems. These side effects can be serious, and managing them effectively is still a challenge. ^{6 7 8 9 10}

What makes the drug Axicabtagene Ciloleucel unique for treating Large B-Cell Lymphoma?

Axicabtagene Ciloleucel is a unique treatment for Large B-Cell Lymphoma because it is a type of CAR T-cell therapy, which involves modifying a patient's own immune cells to better recognize and attack cancer cells, offering a personalized approach compared to traditional chemotherapy. ^{11 12 13 14 15}

Research Team

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 (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]

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]

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 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]

References

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

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

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

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

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

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]

4. United States 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. [2021]

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

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]

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

CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies. [2021]

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Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study. [2019]

10. New Zealand pubmed.ncbi.nlm.nih.gov

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12. Thailand pubmed.ncbi.nlm.nih.gov

Efficacy of dose dense doxorubicin and cyclophosphamide followed by paclitaxel versus conventional dose doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel in patients with node-positive breast cancer. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression. [2020]

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

Integration of docetaxel into adjuvant breast cancer treatment regimens. [2018]

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Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer. [2020]