Axicabtagene Ciloleucel for Follicular Lymphoma

(ZUMA-22 Trial)

Recruiting at 51 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kite, A Gilead Company

Must not be taking: CD19-targeted, CAR therapy

Disqualifiers: CNS disorder, Cardiac disease, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 cycles (21-28 days per cycle)

230 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is test how well the study drug, axicabtagene ciloleucel, works in participants with relapsed/refractory follicular lymphoma

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Axicabtagene Ciloleucel for Follicular Lymphoma?

Research shows that Axicabtagene Ciloleucel (axi-cel) is effective for patients with relapsed or refractory follicular lymphoma, with high response rates and durable remissions observed in the ZUMA-5 study. It is considered a promising option for patients who have not responded to other treatments. ^{1 2 3 4 5}

Is Axicabtagene Ciloleucel (Yescarta) safe for humans?

Axicabtagene ciloleucel (Yescarta) has been used in various studies for different types of lymphoma, showing a manageable safety profile. Common side effects include cytokine release syndrome (a reaction that can cause fever and low blood pressure), neurological issues, infections, fever, diarrhea, nausea, low blood pressure, and fatigue. ^{1 2 3 6 7}

How is the treatment axicabtagene ciloleucel unique for follicular lymphoma?

Axicabtagene ciloleucel is a unique treatment for follicular lymphoma because it is a CAR-T cell therapy, which uses the patient's own modified immune cells to target and destroy cancer cells, offering high response rates and durable remissions even in patients with difficult-to-treat cases. ^{1 2 3 4 8}

Research Team

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Eligibility Criteria

This trial is for adults with a confirmed diagnosis of follicular lymphoma who need treatment and have at least one measurable lesion. They must have had the disease return or not respond after initial therapy, including those whose disease came back within 24 months or after two treatments. Pregnant women, individuals with certain nervous system disorders, severe neuropathy, active infections (including HIV and hepatitis), autoimmune diseases, cardiac issues in the past six months, prior CD19-targeted therapies or CAR T-cell therapies cannot participate.

Inclusion Criteria

My cancer returned or didn't respond after initial treatment and it's considered high-risk.

At least 1 measurable lesion per the Lugano Classification {Cheson 2014}

I need treatment for my condition.

Exclusion Criteria

History of autoimmune disease

I have been diagnosed with small lymphocytic lymphoma.

I have severe nerve pain or numbness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either axicabtagene ciloleucel or standard of care therapy, including Rituximab-based regimens

6-12 cycles (21-28 days per cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Long-term Follow-up

Participants who received axicabtagene ciloleucel transition to a separate study for continued monitoring

Remainder of 15 years

Treatment Details

Interventions

• Axicabtagene Ciloleucel

Trial Overview The study is testing axicabtagene ciloleucel against standard care drugs like Vincristine, Prednisone, Bendamustine etc., to see which works better for relapsed/refractory follicular lymphoma. Participants will be randomly assigned to receive either the study drug or one of the standard care options.

Participant Groups

Group I: Axicabtagene Ciloleucel Experimental Treatment 3 Interventions

Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.

Group II: Standard of Care Therapy Active Control 7 Interventions

Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2

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) is an effective CAR-T therapy for relapsed/refractory follicular lymphoma, demonstrating high response rates and durable remissions in patients with challenging disease characteristics.

The ZUMA-5 study indicates that axi-cel has manageable toxicities and should be considered a standard treatment option for patients with relapsed/refractory follicular lymphoma beyond second-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Management of Follicular Lymphoma: Current Perspectives on Clinical Utility, Patient Selection and Reported Outcomes. Mohty, R., Kharfan-Dabaja, MA., Chavez, JC.[2023]

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 a retrospective study of 275 patients with relapsed/refractory large B-cell lymphoma (LBCL) receiving axicabtagene ciloleucel (axi-cel), the overall response rate was 82% and the complete response rate was 64%, demonstrating strong efficacy similar to the original ZUMA-1 trial.

Safety profiles showed that 7% of patients experienced severe cytokine release syndrome and 31% had neurotoxicity, with a nonrelapse mortality rate of 4.4%, indicating manageable risks associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Nastoupil, LJ., Jain, MD., Feng, L., et al.[2022]

Yescarta (axicabtagene ciloleucel) is an engineered T-cell therapy that showed a 66% overall response rate and a 47% complete response rate in treating relapsed or refractory diffuse large B-cell lymphoma, based on a phase II study with a median follow-up of 15.1 months.

The therapy was associated with manageable adverse events, including cytokine release syndrome and neurological issues, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. Papadouli, I., Mueller-Berghaus, J., Beuneu, C., et al.[2022]

Axicabtagene ciloleucel is an innovative CAR T-cell therapy approved for treating relapsed or refractory follicular lymphoma, showing high rates of durable responses in patients who have undergone multiple prior treatments.

The therapy has a manageable safety profile, making it a significant advancement for patients with this challenging form of non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma. Cohen, JA., Ghobadi, A.[2022]

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

Axicabtagene Ciloleucel in the Management of Follicular Lymphoma: Current Perspectives on Clinical Utility, Patient Selection and Reported Outcomes. [2023]

5. 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]

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

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. [2022]

7. England pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma. [2022]