Long-term Follow-up of CAR T Cell Therapy

Recruiting at 9 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

500 Participants Needed

Trial Summary

What is the purpose of this trial?

Long-term follow-up of patients exposed to an AUTO CAR T cell therapy for up to 15 years following their first AUTO CAR T cell therapy infusion.

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.

What data supports the effectiveness of the treatment AUTO CAR T cell therapy?

Research on similar CAR T cell therapies, like those targeting CD19, shows high initial response rates in treating certain blood cancers, with many patients achieving complete remission. However, maintaining these responses over the long term remains a challenge, as relapses can occur. ^{1 2 3 4 5}

What safety data exists for CAR T cell therapy in humans?

CAR T cell therapy has shown effectiveness in treating certain blood cancers, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues. Long-term effects may include low blood cell counts, infections, and potential secondary cancers, with ongoing research to better understand and manage these risks. ^{1 6 7 8 9}

How is AUTO CAR T cell therapy different from other treatments for this condition?

AUTO CAR T cell therapy is unique because it involves reprogramming a patient's own T cells to specifically target and destroy cancer cells, combining the precision of antibodies with the powerful functions of T cells. This personalized approach can lead to high response rates in patients with certain types of cancer, such as B-cell malignancies, and offers a novel option for those who have not responded to traditional treatments. ^{1 3 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Late Events after Treatment with CD19-Targeted Chimeric Antigen Receptor Modified T Cells. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Parameters of long-term response with CD28-based CD19 chimaeric antigen receptor-modified T cells in children and young adults with B-acute lymphoblastic leukaemia. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cell Therapy for Pediatric B-ALL: Narrowing the Gap Between Early and Long-Term Outcomes. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicities associated with adoptive cellular therapies. [2022]

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

Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. [2023]

9. United Arab Emirates 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy. [2023]

11. Czech Republic pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

[New treatment for patients with therapy-resistant lymphoma: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy]. [2021]