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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety of a treatment combining CAR T-cell therapy, specifically the drug axicabtagene ciloleucel, with radiation for patients whose follicular lymphoma has returned or not responded to previous treatments. Participants will have their white blood cells collected to create the CAR T-cells, followed by radiation and chemotherapy before receiving the axicabtagene ciloleucel infusion. This trial may suit those diagnosed with follicular lymphoma, whose disease has returned or resisted two or more past treatments, and who have at least one lesion measurable on a scan. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that axicabtagene ciloleucel has a manageable safety record based on previous studies. In long-term follow-ups, patients with certain types of lymphoma experienced lasting positive responses, and the treatment's safety remained consistent. Side effects, or adverse events, were generally expected and could be handled using established guidelines.

One study compared axicabtagene ciloleucel to a similar treatment and found it had more frequent side effects. However, these side effects were not surprising and were managed using existing practices. The FDA has already approved this treatment for other conditions, indicating a known level of safety.

Overall, while side effects occur, they are usually manageable, and the treatment has a well-defined safety record based on previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for follicular lymphoma, which typically involve chemotherapy and monoclonal antibodies, axicabtagene ciloleucel is a type of CAR T-cell therapy. This treatment is unique because it uses the patient's own genetically modified T-cells to target and destroy cancer cells. Researchers are excited about axicabtagene ciloleucel because it represents a personalized approach with the potential for long-lasting remission, offering hope for patients who may not respond to conventional therapies. Additionally, combining this with radiotherapy could enhance its effectiveness by priming the cancer cells for the immune attack.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that axicabtagene ciloleucel, a type of CAR T-cell therapy, holds strong potential for treating follicular lymphoma. In one study, 92% of patients responded to the treatment, and 84% achieved complete remission, with no signs of cancer detected. A follow-up analysis revealed that patients lived over five years without their cancer worsening. In this trial, participants will receive axicabtagene ciloleucel following radiotherapy, suggesting that this combination could effectively treat relapsed or difficult-to-treat follicular lymphoma. ^{3 6 7 8 9}

Who Is on the Research Team?

Susan Wu, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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]

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 (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 (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]

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]

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]

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 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00668

Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene ... The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40536814/

Clinical, tumor, and product features associated with ... Clinical, tumor, and product features associated with outcomes after axicabtagene ciloleucel therapy in follicular lymphoma. J Clin Invest ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1098301524023349

Cost-Effectiveness of Axicabtagene Ciloleucel for Adult ... Relapse, recurrence, and disease burden remain common in follicular lymphoma; 19% of patients relapse within 2 years of treatment, and treatment toxicity ...

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2121/500351/Comparative-Effectiveness-of-Axicabtagene

Comparative Effectiveness of Axicabtagene Ciloleucel Vs ... In patients of all ages, ORR was 92% in axi-cel vs 67% in SoC, and CR rate was 84% vs 37%. Because of varying follow-up lengths by treatment ( ...

5. yescarta.com yescarta.com/clinical-trial-results

YESCARTA® (axicabtagene ciloleucel) Clinical Trial Results For LBCL patients whose cancer returned after their first treatment: YESCARTA showed improved results compared to standard therapy. Trial in LBCL (2nd line). A ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41100801/

Five-Year Follow-Up Analysis of ZUMA-5 The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02348216

NCT02348216 | Study Evaluating the Safety and Efficacy of ... A Comparison of Two-Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients With Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38179688/

Comparative efficacy and safety of tisagenlecleucel and ... Tisa-cel (n = 53) was associated with better safety outcomes than axi-cel (n = 124), reflected by lower rates of any grade and grade ≥3 cytokine release ...

9. yescartahcp.com yescartahcp.com/large-b-cell-lymphoma/safety

Safety - YESCARTA® (axicabtagene ciloleucel) YESCARTA demonstrated a well-characterized safety profile; AEs were managed per established guidance. 1 Consistent safety profile in both clinical trials and ...