CAR T-cell Therapy for Neuroblastoma

Navin Pinto, MD profile photo
Overseen ByNavin Pinto, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy for individuals with neuroblastoma, a cancer that often resists standard treatments. The goal is to assess the safety and effectiveness of using the patient's own immune cells, modified to target the cancer. Participants will receive these modified cells after undergoing chemotherapy to prepare their bodies. The trial seeks individuals with neuroblastoma that has returned or persisted despite other treatments. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic corticosteroids (unless it's a small replacement dose) at least 7 days before joining. You also need to be off chemotherapy or biologic therapy for at least 7 days before starting the trial. If you're on anti-tumor antibody therapy, you need to wait 3 half-lives or 30 days, whichever is shorter, before enrolling.

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

Research has shown that CAR T-cell therapy, which targets CD171 for treating neuroblastoma, appears safe. Studies have found that targeting CD171 does not harm important organs in animal tests with rhesus macaques. This suggests the treatment might not lead to serious side effects in vital organs.

In early human tests, CAR T-cell therapy for neuroblastoma has been safe and feasible, though scientists continue to work on enhancing its effectiveness. It is important to note that this treatment remains in the early stages of human testing, so researchers are determining the optimal dose.

Overall, while early studies have shown the therapy to be well-tolerated, more research is needed to fully understand its safety in humans as it progresses through clinical trials.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about CAR T-cell therapy for neuroblastoma because it represents a personalized approach that directly targets cancer cells. Unlike traditional treatments like chemotherapy or radiation, which can affect both healthy and cancerous cells, CAR T-cell therapy uses a patient's own immune cells, engineered to recognize and attack neuroblastoma cells specifically. This treatment involves modifying T cells to express CD171-specific CARs, which allow them to identify and destroy cancer cells more efficiently. Additionally, the therapy includes variations in generation and spacer length, which researchers believe may enhance the effectiveness and persistence of the T cells in the body. These innovative features give hope for improved outcomes with potentially fewer side effects compared to conventional therapies.

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

Research has shown that a new treatment using CD171-specific CAR T cells could help treat neuroblastoma, a type of cancer. CD171 is a protein found on many neuroblastoma cells, making it a good target for treatment. Early lab studies demonstrated that these CAR T cells can successfully attack neuroblastoma cells by recognizing this protein. They have also been effective against similar proteins in other types of solid tumors, suggesting potential benefits for neuroblastoma patients. This trial will evaluate different generations of CD171-specific CAR T cells, with participants receiving either 2nd or 3rd generation CAR T cells. While these results are promising, further research is needed to confirm their effectiveness in people with neuroblastoma.23678

Who Is on the Research Team?

CA

Catherine Albert, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 26 years old with high-risk neuroblastoma or ganglioneuroblastoma that's resistant to standard treatments. They must have a life expectancy of at least 8 weeks, be in relatively stable health, and not have received certain recent therapies like allogeneic stem cell transplants.

Inclusion Criteria

My organs are functioning well.
My cancer can be measured or seen on tests.
I was diagnosed with high-risk neuroblastoma or it spread after I turned 18 months.
See 13 more

Exclusion Criteria

I have a condition that affects my immune system or bone marrow.
I am currently suffering from a severe infection.
I have a history of or currently have significant brain-related health issues.
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Generation

T cells are isolated, selected, transduced with a lentivirus to express CD171 CAR, and expanded in culture

4-6 weeks

Lymphodepletion and T Cell Infusion

Participants receive lymphodepletion chemotherapy followed by infusion of CAR+ T cells

1 week

Intensive Follow-up

Participants are monitored intensely for 6 weeks with serial blood testing and disease status re-evaluation

6 weeks

Long-term Follow-up

Participants are followed bi-annually for 5 years, then annually for 10 years to monitor long-term health effects

15 years

What Are the Treatments Tested in This Trial?

Interventions

  • Patient Derived CD171 specific CAR T cells
Trial Overview The ENCIT-01 study tests different versions of genetically engineered T cells designed to target CD171 on neuroblastoma cells. It aims to find the highest dose patients can tolerate without severe side effects. These T cells are taken from the patient, modified in the lab, then given back to attack the cancer.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: C: Long Spacer 2nd Generation CE7R CAR T CellsExperimental Treatment1 Intervention
Group II: B: 3rd Generation CE7R CAR T CellsExperimental Treatment1 Intervention
Group III: A: 2nd Generation CE7R CAR T CellsExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials
319
Recruited
5,232,000+

Ben Towne Center for Childhood Cancer Research

Collaborator

Trials
1
Recruited
70+

The Evan Foundation

Collaborator

Trials
5
Recruited
240+

Published Research Related to This Trial

Despite the integration of anti-GD2 monoclonal antibody therapy, the 5-year overall survival rate for high-risk neuroblastoma patients remains around 50%, highlighting the need for improved treatment options.
CAR T cell therapy has shown promise in early clinical trials for neuroblastoma, demonstrating safety and feasibility, but challenges such as T cell persistence and an immunosuppressive tumor environment need to be addressed to enhance its efficacy.
CAR T Cell Therapy for Neuroblastoma.Richards, RM., Sotillo, E., Majzner, RG.[2023]

Citations

Preclinical Assessment of CD171-Directed CAR T-cell ...We have focused on CD171 (L1-CAM), an abundant cell surface molecule on neuroblastomas and, specifically, on the glycosylation-dependent tumor-specific epitope ...
What we learned from bench to bedside with the ...We developed a CAR specific for CD171, an antigen expressed in several solid tumors including neuroblastoma, the most common extracranial tumor in childhood ...
CAR T Cell Therapy for NeuroblastomaIn this review, we summarize the clinical trials that have been completed or are underway for CAR T cell therapy in neuroblastoma.
CD171- and GD2-specific CAR-T cells potently target ...Both CD171 and GD2 are effective targets on human retinoblastoma cell lines, and CAR-T cell therapy is highly effective against retinoblastoma in vitro.
NCT02311621 | Engineered Neuroblastoma Cellular ...Autologous CD4 and CD8 cells are lentivirally transduced to generate patient-derived CD171 specific CAR T cells also expressing an EGFRt. Patients will receive ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/27390347/
Preclinical Assessment of CD171-Directed CAR T-cell ...Our preclinical assessment of the CE7 epitope on CD171 supports its utility and safety as a CAR T-cell target for neuroblastoma immunotherapy.
CAR T Cell Therapy for Neuroblastoma - PMC - PubMed CentralIn early phase clinical trials, CAR T cell therapy for neuroblastoma has proven safe and feasible, but significant barriers to efficacy remain.
Tumor-Derived Extracellular Vesicles Impair CD171- ...We here evaluated the role of tumor-derived extracellular vesicles on the efficacy of CAR T cells targeting the neuroblastoma-specific antigen, CD171.
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