Axicabtagene Ciloleucel for Non-Hodgkin's Lymphoma

(ZUMA-5 Trial)

No longer recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kite, A Gilead Company

Disqualifiers: Transformed FL, Small lymphocytic, 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

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called axicabtagene ciloleucel for individuals with non-Hodgkin's lymphoma, a type of blood cancer. The treatment modifies the participant's own white blood cells in a lab to enhance their ability to fight cancer. The trial aims to determine if this treatment can reduce cancer symptoms and ensure its safety. Individuals whose lymphoma has worsened after at least two different treatments might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you're on conventional systemic therapy, you need to stop it 2 weeks or 5 half-lives before the procedure, whichever is shorter. For immune checkpoint therapy, you need to stop 3 half-lives before the procedure.

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 people with non-Hodgkin's lymphoma. In earlier studies, about 90% of patients experienced a significant side effect called cytokine release syndrome (CRS), with some facing severe reactions. Despite these side effects, many patients showed positive changes in their condition.

Although these side effects might seem concerning, axicabtagene ciloleucel is already approved by the FDA for certain other types of lymphoma. This approval suggests that, despite the risks, the benefits can outweigh them for some patients. Anyone considering joining a trial should discuss these potential side effects with their doctor and weigh them against the possible benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Axicabtagene ciloleucel is unique because it uses CAR T-cell therapy, a cutting-edge approach where a patient's own T cells are modified to better recognize and fight cancer cells. Unlike traditional treatments for Non-Hodgkin's Lymphoma, such as chemotherapy or monoclonal antibodies, this therapy offers a targeted attack on cancer cells by enhancing the body's immune response. Researchers are excited about axicabtagene ciloleucel because it has the potential to provide more durable remissions with fewer side effects than conventional therapies.

What evidence suggests that axicabtagene ciloleucel might be an effective treatment for non-Hodgkin's lymphoma?

Studies have shown that axicabtagene ciloleucel effectively treats a type of non-Hodgkin's lymphoma that recurs or resists treatment. One study found that patients with this condition had a five-year survival rate of 83.4% specific to their lymphoma. This treatment uses the patient's own modified white blood cells to target and attack cancer cells, which has succeeded in previous patients. Research indicates that this method leads to a good response rate, making it a promising option for those unresponsive to other treatments. These findings suggest that axicabtagene ciloleucel is a highly effective treatment for this type of lymphoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Are You a Good Fit for This Trial?

Adults with relapsed or refractory indolent Non-Hodgkin Lymphoma, specifically follicular lymphoma or marginal zone lymphoma that worsened after at least two prior treatments. Participants must have measurable disease, no CNS lymphoma involvement, and be able to stop current therapies before leukapheresis. They should be in good physical condition (ECOG 0-1) and not pregnant or breastfeeding.

Inclusion Criteria

My lymphoma has not affected my brain or spinal cord.

Individual is not pregnant or breastfeeding (female individuals only) and is willing to use birth control from the time of consent through 12 months following chimeric antigen receptor (CAR) T cell infusion (both male and female individuals)

My lymphoma has worsened after two or more treatments.

Exclusion Criteria

My cancer is classified as Grade 3b follicular lymphoma.

My lymphoma has changed from a less aggressive type to a more aggressive one.

My lymphoma affects my heart or I need urgent cancer treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Participants undergo leukapheresis to collect white blood cells for manufacturing

1 week

Conditioning Chemotherapy

Participants receive conditioning chemotherapy with cyclophosphamide and fludarabine for 3 days

1 week

Treatment

Participants are infused with axicabtagene ciloleucel and monitored in a hospital for a minimum of 7 days

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24-60 months

Long-term Follow-up

Participants transition to a long-term follow-up study for the remainder of the 15-year follow-up assessments

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Axicabtagene Ciloleucel
• Cyclophosphamide
• Fludarabine

Trial Overview The trial is testing axicabtagene ciloleucel, a treatment made from the patient's own genetically modified white blood cells designed to fight cancer. It also involves pre-treatment with Cyclophosphamide and Fludarabine. The goal is to see if this approach is effective (aiming for a 70% response rate) and safe for patients.

How Is the Trial Designed?

Group I: axicabtagene ciloleucel Experimental Treatment 3 Interventions

Participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, followed by a single infusion of CAR transduced autologous T cells.

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?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Citations

1. 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 ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5115/534253/Efficacy-and-Safety-of-Axicabtagene-Ciloleucel-Axi

Efficacy and Safety of Axicabtagene Ciloleucel (Axi-cel) for the ... This analysis demonstrated the consistent efficacy of Axi-cel in Chinese R/R NHL patients, while NE of any grade and ≥grade 3 were lower.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5987753/

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T ... Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute.

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

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 ...

5. targetedonc.com targetedonc.com/view/axi-cel-efficacy-in-r-r-indolent-non-hodgkin-lymphoma-sustained-at-5-years

Axi-Cel Efficacy in R/R Indolent Non-Hodgkin Lymphoma ... The 5-year lymphoma specific OS rate was 83.4%. “Collectivley, these long-term data support axi-cel as a highly effective therapeutic approach ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6928/506107/Efficacy-and-Safety-of-Axicabtagene-Ciloleucel-Axi

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 ...

7. 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6990602/

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.

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

Safety - YESCARTA® (axicabtagene ciloleucel) CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin ...