CAR T-Cell Therapy + Radiotherapy for Follicular Lymphoma

Overseen By Susan Wu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Rituximab, Aminoglycosides

Disqualifiers: Transformed FL, Invasive malignancy, 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

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{6 7 8 9 10}

How 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. ^{2 4 9 11 12}

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.

Research Team

Susan Wu, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility 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.

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

Treatment Details

Interventions

• Axicabtagene Ciloleucel
• Radiotherapy

Trial Overview 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.

Participant Groups

Group I: Axicabtagene Ciloleuce Experimental Treatment 6 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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

The ZUMA-5 trial demonstrated that axicabtagene ciloleucel (axi-cel) provides durable responses in patients with relapsed/refractory follicular lymphoma, showing significant improvements in overall survival and progression-free survival compared to the SCHOLAR-5 control cohort.

With a median follow-up of 29.4 months for ZUMA-5 and 25.4 months for SCHOLAR-5, the analysis confirmed that axi-cel's efficacy remains strong over time, with hazard ratios indicating a 48% reduction in the risk of death and a 72% reduction in the risk of disease progression compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Palomba, ML., Ghione, P., Patel, AR., et al.[2023]

In a phase 2 trial involving 111 patients with refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 82%, with 54% achieving a complete response, indicating its efficacy as a treatment option.

The treatment was associated with significant adverse events, including neutropenia in 78% of patients and neurologic events in 28%, highlighting the need for careful monitoring of safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. Neelapu, SS., Locke, FL., Bartlett, NL., et al.[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]

Axicabtagene ciloleucel (axi-cel) is an effective CAR T-cell therapy targeting CD19, showing high response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies, particularly after two or more lines of prior treatment.

Axi-cel is FDA-approved for adult patients with specific types of B-cell lymphomas, including diffuse large B-cell lymphoma, and is currently being studied for its efficacy in other B-cell malignancies in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. Sharma, P., King, GT., Shinde, SS., et al.[2018]

In a phase 1 trial involving 12 patients with relapsed/refractory large B-cell lymphoma, the combination of CD19-directed CAR T-cell therapy (axi-cel) and the 4-1BB agonist utomilumab showed a manageable safety profile with no dose-limiting toxicities observed.

The treatment resulted in a high objective response rate of 75%, with 58% of patients achieving a complete response, suggesting that this combination may enhance the efficacy of CAR T-cell therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Jain, MD., Miklos, DB., Jacobson, CA., et al.[2023]

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]

In the ZUMA-12 study involving 40 patients with high-risk large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high complete response rate of 78% and an overall response rate of 89%, indicating its effectiveness as a first-line treatment.

The safety profile of axi-cel was manageable, with only 8% of patients experiencing severe cytokine release syndrome and 23% experiencing neurological events, and no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Neelapu, SS., Dickinson, M., Munoz, J., et al.[2023]

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]

Axicabtagene ciloleucel and tisagenlecleucel are FDA-approved CAR T cell therapies specifically designed to target CD19 in patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma, marking a significant advancement in cellular immunotherapy.

Despite their transformative potential, there are ongoing concerns about the appropriate use and potential short- and long-term toxicities of these therapies, prompting expert consensus to guide clinicians in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Jain, T., Bar, M., Kansagra, AJ., et al.[2020]

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]

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 (Yescarta) is an FDA-approved CAR T-cell therapy specifically designed to target CD19-expressing cells in patients with non-Hodgkin B-cell lymphoma who have not responded to previous chemotherapy, highlighting its role in treating drug-resistant lymphoma.

The therapy utilizes the patient's own T cells, which are modified to better recognize and attack cancer cells, demonstrating a novel approach to improve outcomes in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yescarta: A New Era for Non-Hodgkin Lymphoma Patients. AlDallal, SM.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

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]

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

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]

3. 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]

4. Spain pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. [2018]

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

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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. [2023]

8. 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]

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

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]

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

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

11. 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]

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

Yescarta: A New Era for Non-Hodgkin Lymphoma Patients. [2020]