20 Participants Needed

Axicabtagene Ciloleucel for Non-Hodgkin Lymphoma

KC
Overseen ByKelly Chyan, MPH
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Stanford University
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Axicabtagene Ciloleucel, a type of CAR T-cell therapy, to determine its safety for people with Large B Cell Lymphoma (LBCL) who are likely to experience a relapse. The trial aims to assess whether this treatment can benefit those at high risk who have already tried one other treatment for LBCL. Suitable candidates have aggressive forms of B cell lymphoma and at least one measurable tumor on a scan. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that Axicabtagene Ciloleucel is likely to be safe for humans?

Research has shown that Axicabtagene Ciloleucel has been tested for safety in patients with non-Hodgkin lymphoma. In earlier studies, some patients experienced cytokine release syndrome (CRS), a reaction that can be serious or life-threatening. This occurred in about 90% of patients who received the treatment. However, the FDA has already approved this treatment for certain types of lymphoma, indicating that its safety is well understood.

As this trial is in an early stage, the main goal is to ensure the treatment's safety for a new group of patients. Researchers will closely monitor any side effects. Participants will receive careful monitoring to ensure their safety.12345

Why do researchers think this study treatment might be promising?

Axicabtagene Ciloleucel (Axi-Cel) is unique because it uses CAR T-cell therapy to target non-Hodgkin lymphoma, specifically high-risk relapsed/refractory large B-cell lymphoma (LBCL). Unlike traditional treatments like chemotherapy and radiation, which attack both cancerous and healthy cells, Axi-Cel reprograms a patient's own immune cells to recognize and destroy cancer cells more precisely. This targeted approach not only promises fewer side effects but also offers hope for patients who haven't responded well to standard therapies. Researchers are particularly excited about its potential to provide long-term remission with just one dose.

What evidence suggests that Axicabtagene Ciloleucel might be an effective treatment for Non-Hodgkin Lymphoma?

Research shows that axicabtagene ciloleucel (Axi-Cel) can effectively treat large B-cell lymphoma (LBCL). One study found that patients with LBCL, which returned early or didn't respond to other treatments, lived longer with Axi-Cel compared to other options. Another study on patients with non-Hodgkin lymphoma, a type of LBCL, reported positive results with Axi-Cel, indicating it helps manage the disease. Real-world data supports these findings, showing improvement in patients who didn't respond well to previous treatments. This trial will evaluate Axi-Cel in two phases: a Safety Run-in phase and a Phase 1b, to further assess its efficacy for those at high risk of the disease returning.23567

Who Is on the Research Team?

SD

Saurabh Dahiya, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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

Willingness to practice birth control for specified duration if of child-bearing potential
I am fully active or restricted in physically strenuous activity but can do light work.
My lymphoma is high-risk with elevated LDH levels.
See 8 more

Exclusion Criteria

My lymphoma has spread to my brain or spinal cord.
History of allergic reactions or severe infusion reaction to Axi-Cel
I have previously undergone CAR-T or adoptive cell therapy.
See 7 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Phase 1bExperimental Treatment1 Intervention
Group II: Safety Run-in phaseActive Control1 Intervention

Axicabtagene Ciloleucel is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Yescarta for:
🇪🇺
Approved in European Union as Yescarta for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials
2,527
Recruited
17,430,000+

Kite Pharma

Collaborator

Trials
2
Recruited
40+

Published Research Related to This Trial

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.
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.
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 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.
Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma.Cohen, JA., Ghobadi, A.[2022]

Citations

Safety and efficacy of axicabtagene ciloleucel in refractory ...We provide an overview of axi-cel therapy, including efficacy and safety data, along with a practical discussion of current treatment considerations.
Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene ...Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 ...
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 ...
Survival with Axicabtagene Ciloleucel in Large B-Cell ...Axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than ...
Real World Evidence | YESCARTA® (axicabtagene ciloleucel)Data were collected retrospectively from 298 patients with R/R LBCL who underwent leukapheresis at 17 US institutions as of September 30, 2018, with the intent ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/41100801/
Five-Year Follow-Up Analysis of ZUMA-5The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment ...
Efficacy and Safety of Axicabtagene Ciloleucel (Axi-cel) for the ...We reported best objective response rate (bORR), best complete response (bCR) rate and adverse events of special interest (AESI), including cytokine release ...
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