Axicabtagene Ciloleucel for Follicular Lymphoma
(ZUMA-22 Trial)
Recruiting in Palo Alto (17 mi)
+51 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Kite, A Gilead Company
Must not be taking: CD19-targeted, CAR therapy
Disqualifiers: CNS disorder, Cardiac disease, Autoimmune, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
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.12345
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.12367
How is the treatment axicabtagene ciloleucel unique for follicular lymphoma?
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.
See 2 more
Exclusion Criteria
History of autoimmune disease
I have been diagnosed with small lymphocytic lymphoma.
I have severe nerve pain or numbness.
See 15 more
Trial 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 (CAR T-cell Therapy)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: Axicabtagene CiloleucelExperimental Treatment3 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 TherapyActive Control7 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)Duarte, CA
Stanford Health CareStanford, CA
The University of Kansas HospitalWestwood, KS
Henry-Joyce Cancer ClinicNashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Kite, A Gilead CompanyLead Sponsor
References
New Second-Line Treatment for B-Cell Lymphoma. [2022]Axicabtagene ciloleucel (Yescarta) has been approved for use as a second-line drug in patients with large B-cell lymphoma who are resistant to, or who relapse within 12 months of, first-line chemoimmunotherapy.Confirming the patient's identity and matching it to the drug are critical as this is an autologous infusion. Nurses should premedicate patients to minimize the risk of hypersensitivity reactions.
Interim Phase 2 ZUMA-5 Results Show Promise for Axi-Cel in R/R iNHL. [2021]Results from an interim analysis of the phase 2 ZUMA-5 study showed that axicabtagene ciloleucel (axicel;Yescarta) demonstrated significant and durable clinical benefit in patients with relapsed or refractory indolent non-Hodgkin lymphoma, with high overall response rate (ORR) and complete response (CR) rate observed. It also had a manageable safety profile.
Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting.
Axicabtagene Ciloleucel in the Management of Follicular Lymphoma: Current Perspectives on Clinical Utility, Patient Selection and Reported Outcomes. [2023]Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) that has shown efficacy in B-cell non-Hodgkin's lymphoma. It has shown high efficacy in relapsed/refractory follicular lymphoma (FL) even in the presence of high risk features (early relapse, heavily pretreated patients and bulky disease). Treatment options for R/R follicular lymphoma do not offer long-term remissions, especially in the third-line setting. Axi-cel was studied in R/R FL in the ZUMA-5 study, which showed high response rates with durable remissions. Axi-cel was associated with anticipated but manageable toxicities. Long-term follow up may be able to inform the potential for cure of FL. Axi-cel should be part of the standard of care options for R/R FL beyond second line.
Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. [2021]To evaluate the literature for axicabtagene ciloleucel (axi-cel), a first-in-class chimeric antigen receptor (CAR) T-cell therapy, in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL).
Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. [2022]Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication.
EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]On June 28, 2018, the Committee for Advanced Therapies and the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yescarta for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy. Yescarta, which was designated as an orphan medicinal product and included in the European Medicines Agency's Priority Medicines scheme, was granted an accelerated review timetable. The active substance of Yescarta is axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product whereby a patient's own T cells are harvested and genetically modified ex vivo by retroviral transduction using a retroviral vector to express a chimeric antigen receptor (CAR) comprising an anti-CD19 single chain variable fragment linked to CD28 costimulatory domain and CD3-zeta signaling domain. The transduced anti-CD19 CAR T cells are expanded ex vivo and infused back into the patient, where they can recognize and eliminate CD19-expressing cells. The benefits of Yescarta as studied in ZUMA-1 phase II (NCT02348216) were an overall response rate per central review of 66% (95% confidence interval, 56%-75%) at a median follow-up of 15.1 months in the intention to treat population and a complete response rate of 47% with a significant duration. The most common adverse events were cytokine release syndrome, neurological adverse events, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. IMPLICATIONS FOR PRACTICE: Yescarta (axicabtagene ciloleucel) was the first chimeric antigen receptor T-cell therapy to be submitted for evaluation to the European Medicines Agency and admitted into the "priority medicine" scheme; it was granted accelerated assessment on the basis of anticipated clinical benefit in relapsed/refractory diffuse large B-cell lymphoma, a condition of unmet medical need. Indeed, Yescarta showed an overall response rate of 66% and a complete response rate of 47% with a significant duration and a manageable toxicity that compared very favorably with historical controls. Here the analysis of benefits and risks is presented, and specific challenges with this important novel product are highlighted, providing further insights and reflections for future medical research.
Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma. [2022]Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was recently approved for relapsed or refractory follicular lymphoma following progression on two or more lines of therapy including an anti-CD20 monoclonal antibody with an alkylating agent, providing a therapeutic breakthrough in a subset of indolent non-Hodgkin lymphoma associated with poor clinical outcomes.