Long-term Follow-up of CAR T Cell Therapy

Enrolling by invitation at 11 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Autolus Limited

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tracks patient outcomes for up to 15 years after receiving AUTO CAR T cell therapy, a treatment that modifies a patient's own cells to fight cancer. It serves as a long-term evaluation of the therapy's effectiveness. Individuals who have already received AUTO CAR T cell therapy in a previous clinical study and meet the study requirements may qualify for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that AUTO CAR T cell therapy is likely to be safe for humans?

Studies have shown that AUTO CAR T cell therapy can help some patients with certain blood cancers remain in remission for extended periods, keeping the cancer under control. However, risks are involved. Many patients experience Cytokine Release Syndrome (CRS), a side effect occurring in about 81.8% of cases, causing symptoms like fever, nausea, and tiredness.

There is also a risk of prolonged cytopenia, a significant drop in blood cells, which increases susceptibility to infections. This risk is higher for certain cancers, such as B-cell Acute Lymphoblastic Leukemia (B-cell ALL), compared to Non-Hodgkin Lymphoma (NHL).

Long-term care is crucial because AUTO CAR T cell therapy can lead to other late complications, such as infections and more severe drops in blood cells, which can be serious. Despite these risks, many patients respond well to the therapy.

The current phase of this research indicates that some evidence about the safety of AUTO CAR T cell therapy already exists, but more information is still being collected. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for CAR T cell therapy?

Unlike standard treatments for certain cancers, which often include chemotherapy or radiation, AUTO CAR T cell therapy offers a personalized approach by harnessing the patient’s own immune cells. This innovative treatment involves reprogramming T cells to target and destroy cancer cells more effectively. Researchers are excited because AUTO CAR T cell therapy has the potential to offer long-term remission with fewer side effects compared to traditional options, making it a promising advancement in cancer treatment.

What is the effectiveness track record for AUTO CAR T cell therapy?

Studies have shown that AUTO CAR T cell therapy effectively treats certain cancers. In previous research, about 55% of patients achieved complete remission, with no signs of cancer detected. Of these patients, 60% remained cancer-free for five years. This therapy uses specially modified cells to locate and destroy cancer cells. Research also indicates that AUTO CAR T therapy has successfully treated various blood cancers and shows promise with solid tumors. Overall, these results suggest that AUTO CAR T cell therapy can be a powerful option for long-term cancer control. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients who have previously received AUTO CAR T cell therapy as part of a clinical study. They must have agreed to long-term follow-up and be able to comply with the study's requirements.

Inclusion Criteria

Patients must have provided informed consent for long-term follow-up study prior to participation

Patients must be able to comply with the study requirements

I have received CAR T cell therapy as part of a clinical trial.

Exclusion Criteria

There are no specific exclusion criteria for this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AUTO CAR T cell therapy infusion

1 day

1 visit (in-person)

Follow-up

Long-term monitoring for safety and efficacy, including assessment of SAEs, AESIs, and CAR transgene persistence

15 years

Visits at Month 3, 6, 9, 12 during Year 1, then every 6 months up to Year 5, then yearly up to Year 15

What Are the Treatments Tested in This Trial?

Interventions

• AUTO CAR T cell therapy

Trial Overview The trial involves long-term monitoring of patients treated with AUTO CAR T cell therapy, tracking their health for up to 15 years after their first infusion to assess lasting effects and outcomes.

How Is the Trial Designed?

Group I: AUTO CAR T cell therapy Experimental Treatment 1 Intervention

Patients who received previous treatment with AUTO CAR T Cell Therapy

Who Is Running the Clinical Trial?

Autolus Limited

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

CAR T cell therapy has become an important treatment for certain blood cancers, with three types of anti-CD19 CAR-T cells already approved for use in the Czech Republic, and more trials underway for targeting other cancer-specific antigens.

While the management of CAR-T cell therapy has improved, including updated guidelines for early toxicity, long-term follow-up is essential due to potential late toxicities, highlighting the need for ongoing research to enhance efficacy and reduce side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. Jana, M., Tomáš, J., Michal, K., et al.[2022]

CAR T cell therapy is an effective treatment for relapsed/refractory hematologic cancers, leading to the FDA approval of five products, but it is associated with significant immune-mediated toxicities like cytokine release syndrome (CRS) and neurological issues.

Long-term effects of CAR T cell therapy can include prolonged low blood cell counts, reduced antibody levels, increased risk of infections, and potential development of secondary cancers, highlighting the need for careful monitoring and management of these toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities associated with adoptive cellular therapies. Hansen, DK., Dam, M., Faramand, RG.[2022]

The combination of autologous stem-cell transplantation (ASCT) and CAR30 T-cell therapy was found to be safe and effective in treating relapsed/refractory CD30+ lymphoma, with 83.3% of patients achieving a complete response after treatment.

In a pilot study involving 6 patients, all of whom had previously poor prognoses, the treatment resulted in successful engraftment and maintained responses over a median follow-up of 20.4 months, indicating promising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. Zhang, P., Yang, X., Cao, Y., et al.[2022]

CAR T-cell therapy, particularly targeting CD19, has shown remarkable efficacy with approximately 90% complete response rates in patients with relapsed or refractory acute lymphoblastic leukemia, demonstrating its potential as a powerful treatment for B-cell malignancies.

Ongoing research is focused on enhancing the safety and effectiveness of CAR T cells, including exploring their use in solid tumors and in combination with other therapies, indicating a promising future for this innovative cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy. Maus, MV., June, CH.[2023]

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

In a study of patients who underwent CD19-targeted CAR-T cell therapy for B cell malignancies, 73% were alive and 24% were in complete remission after a median follow-up of 28.1 months, indicating promising long-term efficacy.

The most common late adverse event was hypogammaglobulinemia, affecting 67% of patients, but most late events were not severe, suggesting a generally safe long-term profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late Events after Treatment with CD19-Targeted Chimeric Antigen Receptor Modified T Cells. Cordeiro, A., Bezerra, ED., Hirayama, AV., et al.[2021]

A review of 152 pre-clinical studies on CAR T-cell therapy revealed that only 7.9% were specifically designed to assess or improve safety, indicating a significant gap in safety evaluation prior to clinical use.

Key safety parameters, such as the use of immunocompetent animal models and comprehensive monitoring of physiological responses, were inadequately reported, suggesting that current pre-clinical data may not reliably predict the safety of CAR T-cell therapies in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality Assessment of Pre-Clinical Studies of Chimeric Antigen Receptor T-Cell Therapy Products: A Point of Focus on Safety. Maharshi, V., Diksha, D., Gupta, P.[2022]

A multicenter initiative has been established to comprehensively study the extended toxicities and late effects of CAR T cell therapy, focusing on areas such as neurotoxicity, psychosocial impacts, and immune reconstitution.

The initiative aims to create a systematic framework for investigating adverse events related to CAR T cell therapy, which will help optimize treatment strategies and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells. Shalabi, H., Gust, J., Taraseviciute, A., et al.[2023]

Citations

1. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy This study demonstrated a CR rate of 55%, and 60% of these patients remained in remission at 5 years. Overall, these results demonstrate that ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37055515/

Long-term outcomes following CAR T cell therapy - PubMed In this Review, we summarize long-term follow-up data on efficacy and toxicities from patients treated with CAR T cells targeting CD19 or BCMA.

3. ashpublications.org ashpublications.org/blood/article/146/14/1677/537756/Remission-conversion-drives-outcomes-after-CAR-T

Remission conversion drives outcomes after CAR T-cell ... Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1567576924008324

CAR-T cell therapy: Efficacy in management of cancers ... This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors.

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1650568/full

Long-term follow-up of patients with relapsed/refractory ... In BCMA CAR-T responders, cell expansion peaked at 7–15 days, followed by a gradual decline within 1 month. CAR-T cells became undetectable in all patients ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5877/527643/Long-Term-Outcomes-and-Adverse-Events-of-CAR-T-19

Long-Term Outcomes and Adverse Events of CAR T-19 Cell ... Significant adverse effects were noted, including Cytokine Release Syndrome (CRS) with a mean incidence of 81.8% (95% CI: 76.7% to 86.9%), ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8078596/

Late Effects after Chimeric Antigen Receptor T cell Therapy for ... The risk of prolonged cytopenia post-CAR T-cell therapy is higher in B-cell ALL compared to NHL, based on clinical trials and observational studies.

8. ashpublications.org ashpublications.org/hematology/article/2024/1/109/526152/Late-complications-and-long-term-care-of-adult-CAR

Late complications and long-term care of adult CAR T-cell ... Understand that adult CAR T-cell patients are at risk for a number of late complications (eg, infections, cytopenias) that can be life-threating ...