CAR T-Cell Therapy + Radiotherapy for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Rituximab, Aminoglycosides
Disqualifiers: Transformed FL, Invasive malignancy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?To learn about the safety of a drug called axicabtagene ciloleucel given in combination with radiation therapy to patients with relapsed/refractory FL.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that steroids are permitted, and there is no urgent need for bridging chemotherapy or rituximab between certain procedures. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment Axicabtagene Ciloleucel (Axi-cel) combined with Radiotherapy for Follicular Lymphoma?
Research shows that Axicabtagene Ciloleucel (Axi-cel), a type of CAR T-cell therapy, has been effective in treating relapsed or refractory follicular lymphoma, with high rates of durable response compared to other treatments. This suggests it could be beneficial when combined with radiotherapy for follicular lymphoma.
12345Is CAR T-Cell Therapy (Axicabtagene Ciloleucel) safe for humans?
Axicabtagene ciloleucel (Yescarta) has been shown to have a manageable safety profile in various studies for different types of lymphoma, with common side effects including cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly), neurological events, infections, fever, diarrhea, nausea, low blood pressure, and fatigue. Serious side effects occurred in some patients, but no treatment-related deaths were reported.
678910How is the treatment Axicabtagene Ciloleucel (Yescarta) unique for follicular lymphoma?
Axicabtagene Ciloleucel (Yescarta) is a unique treatment for follicular lymphoma because it uses the patient's own T-cells, which are modified to target and destroy cancer cells expressing the CD19 protein. This approach offers high response rates and durable remissions, especially for patients who have not responded to other treatments.
2491112Eligibility Criteria
This trial is for adults over 18 with Follicular Lymphoma that's come back or hasn't responded after at least two treatments. They should be fairly active (able to care for themselves), have good organ function, and no severe liver issues. Participants need measurable cancer lesions, can have had past radiation if safe, and women able to have children must test negative for pregnancy.Inclusion Criteria
I have had radiation therapy without exceeding normal tissue tolerance.
I have at least 2 tumors that can be measured and are larger than 1 cm.
I am a woman who can have children and have a recent negative pregnancy test.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Radiation
Participants receive bridging radiotherapy as part of the treatment protocol
2 weeks
Chemotherapy
Participants undergo conditioning chemotherapy prior to CAR T-cell infusion
1 week
CAR T-cell Infusion
Participants receive an infusion of axicabtagene ciloleucel
1 day
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of cytokine release syndrome (CRS) and ICANS
4 weeks
Participant Groups
The study tests axicabtagene ciloleucel (a CAR-T cell therapy) combined with radiotherapy in patients with relapsed/refractory Follicular Lymphoma. It aims to assess the safety of this combination treatment.
1Treatment groups
Experimental Treatment
Group I: Axicabtagene CiloleuceExperimental Treatment6 Interventions
Participants will first have a procedure to collect your white blood cells that will be used to make axicabtagene ciloleucel. Then participatns will receive radiation therapy, followed by conditioning chemotherapy and 1 infusion of axicabtagene ciloleucel.
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:
MD Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. [2023]In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data.
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
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).
Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. [2018]B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options. Axi-cel is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, and is also being evaluated in other B-cell malignancies in ongoing clinical trials. In this review we will discuss the mechanism of action of axi-cel, clinical trials leading to its FDA approval, ongoing clinical trials and its potential adverse effects, and will speculate on the future directions of axi-cel and CAR T-cell therapy in general.
Axicabtagene Ciloleucel in Combination with the 4-1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11. [2023]Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4-1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy.
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 as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. [2023]High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.
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.
Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. [2020]Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYMRIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short- and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.
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 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.
Yescarta: A New Era for Non-Hodgkin Lymphoma Patients. [2020]The use of conventional therapeutic approaches in patients with lymphoma demonstrates significant drug resistance leading to poor prognosis with reduced median survival period. T-cell immunotherapy has diverted huge attention of the researchers in recent times to engage in the stated research studies in the pool of chemotherapy-refractory lymphoma patients. B-cell antigen CD19-targeted chimeric antigen receptor (CAR) T-cell products are approved for the treatment of non-Hodgkin B-cell refracting or relapsing lymphoma. The aim of this article is to give an idea about the use of FDA-approved anti-cancer gene therapy, Axicabtagene ciloleucel, marketed under the name of Yescarta®. Axicabtagene ciloleucel is developed from the patients' mononuclear peripheral blood cells during which T cells are orchestrated to articulate a CAR that diverts them to identify CD19-expressing cells. It is used in patients with non-Hodgkin B-cell refracting or relapsing lymphoma who had no response to prior therapeutic regiment involving the use of chemotherapeutics. Here, we review the mode of action, safety, and efficacy of Yescarta.