Axicabtagene Ciloleucel for Non-Hodgkin Lymphoma

Overseen By Kelly Chyan, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Anticonvulsants

Disqualifiers: Pregnancy, CNS disease, Prior CAR-T, others

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

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase Ib study to establish safety of Axi-Cel-2 in patients with Large B Cell Lymphoma (LBCL) who are at high risk of relapse.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 2 weeks or 5 half-lives, whichever is shorter, since any prior systemic therapy before starting the study. This means you may need to stop some medications before participating.

What data supports the effectiveness of the treatment Axicabtagene Ciloleucel for Non-Hodgkin Lymphoma?

Research shows that Axicabtagene Ciloleucel (Yescarta) is effective for patients with relapsed or refractory indolent non-Hodgkin lymphoma, with high response rates and manageable safety. It is also approved for relapsed aggressive B-cell non-Hodgkin lymphoma, showing durable remission rates of about 40%. ^{1 2 3 4 5}

Is Axicabtagene Ciloleucel (Yescarta) safe for humans?

Axicabtagene ciloleucel (Yescarta) has been shown to have a manageable safety profile, but it can cause side effects like cytokine release syndrome (a severe immune reaction), neurological issues, infections, fever, diarrhea, nausea, low blood pressure, and fatigue. These side effects were observed in studies for treating different types of non-Hodgkin lymphoma. ^{1 2 3 5 6}

What makes axicabtagene ciloleucel unique for treating non-Hodgkin lymphoma?

Axicabtagene ciloleucel is a unique treatment because it is a CAR T-cell therapy, which means it uses the patient's own modified immune cells to target and destroy cancer cells, specifically those with the CD19 protein. This approach is different from traditional chemotherapy and offers a new option for patients with relapsed or refractory large B-cell lymphoma who have not responded to other treatments. ^{1 3 5 7 8}

Research Team

Saurabh Dahiya, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults over 18 with high-risk Large B Cell Lymphoma who've had one prior treatment can join. They must have normal organ function, not be pregnant or breastfeeding, agree to use birth control, and cannot have a history of certain cancers or severe reactions to Axi-Cel. Those with central nervous system lymphoma, previous CAR-T therapy, or conditions affecting study participation are excluded.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Willingness to practice birth control for specified duration if of child-bearing potential

My lymphoma is high-risk with elevated LDH levels.

Exclusion Criteria

My lymphoma has spread to my brain or spinal cord.

I have previously undergone CAR-T or adoptive cell therapy.

I have had a transplant from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

First three patients (maximum of 6) will receive 0.5 x 10^6/kg CART cells (25% standard dose) as reinfusion product between days 7 through 14 if CRS/ICANS has resolved to a grade 1 or less.

1-2 weeks

Phase 1b Treatment

Up to 20 evaluable subjects will receive the target dose of AxiCel infusion to evaluate efficacy of Axi-Cel-2 in adults with high risk relapsed/refractory LBCL.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on dose limiting toxicity (DLT) for 28 days after the infusion of Axi-Cel-2.

4 weeks

Treatment Details

Interventions

• Axicabtagene Ciloleucel

Trial Overview The trial is testing the safety of a second infusion of Axicabtagene Ciloleucel (Axi-Cel-2) in patients whose aggressive Non-Hodgkin's Lymphoma has returned after initial treatment. It aims to see if reinfusing can help without causing significant harm.

Participant Groups

Group I: Phase 1b Experimental Treatment 1 Intervention

Up to 20 evaluable subjects will receive the target dose of AxiCel infusion to evaluate efficacy of Axi-Cel-2 in adults with high risk relapsed/refractory LBCL

Group II: Safety Run-in phase Active Control 1 Intervention

First three patients (maximum of 6) will receive 0.5 x 106/kg CART cells (25% standard dose) as reinfusion product between days 7 through 14 if CRS/ICANS has resolved to a grade 1 or less.

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?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Kite Pharma

Collaborator

Trials

2

Recruited

40+

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) 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]

Axicabtagene ciloleucel (Axi-cel) provides more quality-adjusted life years (QALYs) compared to standard chemotherapy for treating relapsed large B-cell lymphoma, but it is not cost-effective in China due to its high price, requiring a price reduction for better economic viability.

In contrast, Axi-cel is considered cost-effective in the United States, with an incremental cost-effectiveness ratio (ICER) of $142,326.94/QALY, which is below the acceptable threshold of $150,000, indicating its potential value in the U.S. healthcare system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States. Li, N., Lei, J., Zhang, J., et al.[2023]

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. 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]

5. 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]

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

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

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

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

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

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States. [2023]