CAR T Cell Therapy for Leukemia and Lymphoma

Recruiting at 7 trial locations

Overseen By Autolus Ltd

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Autolus Limited

Disqualifiers: CNS pathology, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment AUTO1 for leukemia and lymphoma?

Research shows that CAR T cell therapy targeting CD19 has been highly effective, achieving complete remission in up to 90% of patients with a type of leukemia called B-cell acute lymphoblastic leukemia, which is often resistant to chemotherapy. This suggests that similar treatments like AUTO1 could also be effective for leukemia and lymphoma. ^{1 2 3 4 5}

Is CAR T Cell Therapy generally safe for humans?

CAR T Cell Therapy has shown a favorable safety profile in clinical trials, with some studies reporting no severe toxicities like cytokine release syndrome or neurotoxicity. However, rare but serious side effects such as hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation have been reported, which can be fatal if not managed properly. ^{6 7 8 9 10}

How is the treatment AUTO1 different from other treatments for leukemia and lymphoma?

AUTO1 is a CAR T cell therapy that uses genetically modified T cells to target and destroy cancer cells, specifically those expressing the CD19 antigen, which is different from traditional chemotherapy that targets rapidly dividing cells in general. This approach has shown remarkable success in achieving complete remission in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, offering a novel and highly effective option compared to standard treatments. ^{1 2 11 12 13}

What is the purpose of this trial?

This is a Phase Ib study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 in pediatric patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B ALL) and r/r B cell Non-Hodgkin lymphoma (B NHL)

Eligibility Criteria

This trial is for pediatric patients under 18 with relapsed or refractory B-cell acute lymphoblastic leukemia (B ALL) and aggressive mature B-cell non-Hodgkin lymphoma (B NHL). They must have tried at least two systemic therapies, weigh more than 6 kg, and have a performance status score of ≥50%. It's not for those who've had certain treatments less than three months ago or don't meet other specific health criteria.

Inclusion Criteria

I am under 18 years old.

My kidney, liver, lung, and heart functions are all within normal ranges.

I weigh at least 6 kg.

Exclusion Criteria

I have a significant brain or nerve condition.

I had a stem cell transplant less than 3 months ago.

I have had severe side effects from blinatumomab treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Collection of T cells from participants for CAR T cell engineering

1 week

Bridging

Participants may receive additional therapy to control disease while waiting for CAR T cell manufacturing

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion to prepare for CAR T cell infusion

1 week

Treatment Evaluation

Participants receive AUTO1 infusion and are monitored for initial safety and efficacy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• AUTO1

Trial Overview The study tests AUTO1, a CAR T cell therapy targeting CD19 in children with specific types of blood cancer that haven't responded to previous treatments. The aim is to see how safe it is and how well it works against these cancers.

Participant Groups

Group I: AUTO1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Autolus Limited

Lead Sponsor

Trials

9

Recruited

1,000+

Findings from Research

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

Autologous T cells engineered to express chimeric antigen receptors (CARs) targeting CD19 have demonstrated remarkable effectiveness in treating relapsed/refractory B-cell leukemias and lymphomas, as shown in clinical trials.

This CAR T cell therapy approach aims to harness the immune system while minimizing adverse effects like graft-versus-host disease, making it a promising strategy for treating pediatric cancers, including B cell acute lymphoblastic leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recent advances and future directions in CAR-T cell therapy in pediatric oncology]. Ceppi, F., Renella, R., Diezi, M., et al.[2019]

In a study of 47 patients with relapsed/refractory large B cell lymphomas receiving CAR T-cell therapy, changes in PET scan results at 30 days post-infusion were found to be predictive of patient outcomes, with a significant correlation between SUVmean variation and progression-free survival.

Patients with a Deauville score of 4-5 and a decrease in SUVmean had a similar 1-year progression-free survival rate (61-62%) as those with a better score (1-3), while those with an increase in SUVmean had a much poorer survival rate of 33%, highlighting the importance of these metrics in assessing treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. Guidetti, A., Dodero, A., Lorenzoni, A., et al.[2023]

CAR T-cell therapy has shown durable remission in B-cell leukemia and lymphoma, highlighting its potential effectiveness for treating other types of cancers.

Recent advancements in CAR design and clinical application strategies aim to enhance T-cell proliferation and efficacy while minimizing toxicity, making this therapy more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cells: New Approaches to Improve Their Efficacy and Reduce Toxicity. Maus, MV., Powell, DJ.[2018]

In a Phase I trial involving 43 pediatric and young adult patients with leukemia, initial treatment failures were linked to poor CAR T cell expansion and rapid loss of functional CAR T cells after infusion.

For patients who achieved remission, the durability of that remission was associated with higher levels of TNF-α-secreting CAR CD8+ T cells and sufficient CD19 antigen levels at the time of treatment, suggesting these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T cell product and disease attributes predict leukemia remission durability. Finney, OC., Brakke, HM., Rawlings-Rhea, S., et al.[2022]

The study demonstrated that using CRISPR/Cas9 to knock out the TCR gene in ARI-0001 CAR-T cells can effectively disrupt the TCR without significantly altering the T cell phenotype, achieving over 80% efficiency.

While this method shows promise for creating allogeneic CAR-T cells with maintained anti-tumor activity, there are potential safety risks due to possible large deletions in the genome that require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. Maldonado-Pérez, N., Tristán-Manzano, M., Justicia-Lirio, P., et al.[2022]

In a phase 1 trial involving 15 pediatric and young adult patients with relapsed or refractory B-ALL, the dual-targeting CAR T-cell therapy AUTO3 demonstrated a favorable safety profile with no severe toxicities reported and an impressive remission rate of 86% one month post-treatment.

Despite the high initial remission rate, the one-year overall survival rate was 60% and event-free survival rate was 32%, indicating that improvements in the persistence of AUTO3 CAR T-cells are necessary to enhance long-term outcomes and prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Cordoba, S., Onuoha, S., Thomas, S., et al.[2022]

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving remission rates as high as 90% in relapsed/refractory acute lymphoblastic leukemia (ALL), but lower response rates in chronic lymphocytic leukemia (CLL) highlight the need for ongoing research to improve outcomes.

Long-term follow-up indicates that CAR T cell therapy may provide durable remissions, but the emergence of escape pathways necessitates combinatorial treatment strategies and careful toxicity management to enhance safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia. Singh, N., Frey, NV., Grupp, SA., et al.[2018]

CAR T-cell therapy has received FDA approval for treating relapsed/refractory diffuse large B-cell lymphoma, recurrent acute lymphoblastic leukemia, and mantle cell lymphoma, highlighting its growing role in hematological cancer treatment.

Despite its promise, CAR T-cell therapy faces challenges in efficacy and persistence across different hematological malignancies, with over a thousand ongoing clinical trials aimed at addressing these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies. Lin, WY., Wang, HH., Chen, YW., et al.[2021]

In a phase I clinical trial involving 7 patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma, CD7 CAR-T therapy achieved a remarkable 100% complete remission rate by day 28, demonstrating its strong efficacy.

However, the treatment was associated with significant safety concerns, including severe infections leading to the deaths of 2 patients, highlighting the need for careful monitoring of immune reconstitution and potential complications post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy. Chen, W., Shi, H., Liu, Z., et al.[2023]

Chimeric antigen receptor-modified T cells (CAR-Ts) are a promising new treatment for hematological malignancies, showing powerful efficacy against tumor cells by targeting specific cancer-associated antigens.

The review discusses the CAR-T manufacturing process and highlights ongoing clinical trials for various blood cancers, including acute lymphoblastic leukemia and multiple myeloma, indicating a growing interest and development in this area of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. Allegra, A., Innao, V., Gerace, D., et al.[2018]

References

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

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Recent advances and future directions in CAR-T cell therapy in pediatric oncology]. [2019]

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

Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. [2023]

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

Chimeric Antigen Receptor T-Cells: New Approaches to Improve Their Efficacy and Reduce Toxicity. [2018]

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

CD19 CAR T cell product and disease attributes predict leukemia remission durability. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. [2022]

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

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. [2023]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies. [2021]

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

Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy. [2023]

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

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. [2018]