CAR T Cell Therapy for Acute Myeloid Leukemia

Recruiting at 6 trial locations

Overseen by Mark Geyer, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, HIV, HBV, HCV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of using specially modified immune cells to treat cancer patients who haven't responded to other treatments. The goal is to find the highest dose that causes few or mild side effects.

Will I have to stop taking my current medications?

The trial requires that participants stop taking any systemic immunosuppressive agents at least 30 days before treatment, but a physiologic dose of corticosteroids is allowed. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the treatment CD371-YSNVZ-IL18 CAR T cells for acute myeloid leukemia?

Research shows that CAR T-cell therapy has been successful in targeting specific leukemia cells in other studies, such as those targeting CD117 and CD4 markers in acute myeloid leukemia. This suggests potential for similar therapies like CD371-YSNVZ-IL18 CAR T cells to be effective. ^{1 2 3 4 5}

What safety data exists for CAR T Cell Therapy in humans?

CAR T Cell Therapy can cause side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (damage to the nervous system), although these are not common. Careful monitoring is needed due to potential toxicities, especially when targeting certain antigens in blood cancers. ^{1 2 6 7 8}

What makes the CD371-YSNVZ-IL18 CAR T cell treatment unique for acute myeloid leukemia?

The CD371-YSNVZ-IL18 CAR T cell treatment is unique because it targets specific antigens on leukemia cells, which is challenging due to the lack of leukemia-specific targets in acute myeloid leukemia (AML). This therapy aims to overcome immune escape and the suppressive tumor environment, which are significant hurdles in treating AML with CAR T cells. ^{1 5 7 9 10}

Research Team

Mark Geyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for people with a type of blood cancer called Acute Myeloid Leukemia (AML) that has CD371+ expression. It's open to all ages, but kids must be over 1 year old and weigh at least 10kg. Adults need functioning liver and kidneys, no active graft-versus-host disease post-transplant, and can't have had certain treatments recently. Pregnant women or those who could become pregnant must use contraception.

Inclusion Criteria

My AML did not respond to initial treatment attempts.

I am 16 or older and can care for myself with minimal assistance.

My first AML relapse occurred 12 months or more after my initial treatment, and repeating the same treatment is not expected to help.

Exclusion Criteria

I'm sorry, but it seems like the criterion you provided was incomplete. Could you please provide the full criterion so that I can rewrite it for you?

I have or had brain involvement with my cancer but it's been treated.

I am not pregnant or breastfeeding and if I can become pregnant, I am using effective birth control.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CD371-YSNVZ-IL18 CAR T cells to determine the Maximum Tolerated Dose

up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CD371-YSNVZ-IL18 CAR T cells (CAR T-cell Therapy)

Trial Overview Researchers are testing a new therapy using special immune cells called CD371-YSNVZ-IL18 CAR T cells to treat AML. They want to find the highest dose that's still safe with few or mild side effects by gradually increasing the amount given to participants.

Participant Groups

Group I: Step-Down Dose Experimental Treatment 1 Intervention

Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Group II: Dose Level 2 Experimental Treatment 1 Intervention

Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Group III: Dose Level 1 Experimental Treatment 1 Intervention

Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

CAR T-cell therapy shows promise in improving outcomes for patients with acute myeloid leukemia (AML), a condition with historically poor prognosis.

A significant challenge for the effectiveness of CAR T-cell therapy in AML is the identification of specific target antigens on leukemia cells, as well as the risk of immune escape due to changes in these antigens and a suppressive tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current challenges for CAR T-cell therapy of acute myeloid leukemia. Sauer, T., Rooney, CM.[2020]

The study demonstrates that CAR T-cells targeting CD117 can effectively eliminate both healthy and leukemic hematopoietic stem and progenitor cells (HSPCs) in vitro and in mouse models, suggesting a potential therapeutic strategy for acute myeloid leukemia (AML).

In preclinical models, the anti-CD117 CAR T-cells successfully eradicated primary human CD117-positive AML, indicating their efficacy in treating this type of leukemia while sparing most mature hematopoietic cells, which is crucial for maintaining healthy blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells. Myburgh, R., Kiefer, JD., Russkamp, NF., et al.[2021]

CD4 is identified as a promising target for CAR-T cell therapy in treating acute myeloid leukemia (AML), as it is expressed in certain AML subtypes but not on normal hematopoietic stem cells, allowing for targeted treatment.

CD4 redirected CAR-T cells effectively eliminated CD4-expressing AML cells in laboratory settings and demonstrated strong anti-leukemic effects in a mouse model, suggesting potential for clinical application in refractory AML cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells. Salman, H., Pinz, KG., Wada, M., et al.[2020]

CAR T-cell therapy has the potential to improve outcomes for patients with acute myeloid leukemia (AML) by specifically targeting leukemia cells, but there are significant challenges to its effectiveness and safety.

Strategies being explored to enhance CAR T-cell therapy in AML include targeting specific leukemia antigens to reduce side effects, using checkpoint inhibitors to counteract immune suppression caused by leukemia, and developing allogenic CAR T cells to make the treatment more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. Badar, T., Manna, A., Gadd, ME., et al.[2022]

CART-38, a novel CAR T-cell therapy targeting CD38, effectively rejected multiple hematologic malignancies, including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), and multiple myeloma (MM) in xenografted mice, demonstrating its potential efficacy across different age groups.

While CART-38 showed promising results in treating these cancers, it also reduced hematopoietic progenitors in a model of normal human blood cell development, indicating a need for careful monitoring of potential toxicity in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38 as a pan-hematologic target for chimeric antigen receptor T cells. Glisovic-Aplenc, T., Diorio, C., Chukinas, JA., et al.[2023]

Up to 30% of patients with acute myeloid leukemia (AML) show some response to CAR T-cell therapy, but these responses are often not deep or long-lasting, indicating a need for improved treatment strategies.

Common targets for CAR T-cells in AML include CD123, CD33, and CLL-1, but while these therapies can lead to myeloablation and cytokine release syndrome, they rarely cause neurotoxicity, suggesting a relatively safe profile for certain side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. Cummins, K., Gill, S.[2023]

CAR-T cell therapies have revolutionized the treatment of certain blood cancers, with six FDA-approved therapies showing overall response rates between 50% and 100%, but with significant relapse rates of up to 66%.

Next-generation CAR-T cells are being developed to improve efficacy and safety by incorporating advanced features like additional costimulatory domains and safety switches, which may help reduce side effects and expand treatment options for more types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next generations of CAR-T cells - new therapeutic opportunities in hematology? Tomasik, J., Jasiński, M., Basak, GW.[2022]

Acute Myeloid Leukemia (AML) has a low 5-year survival rate of less than 30%, and current treatment options have not significantly changed in decades, highlighting the need for new therapies.

This review identifies potential target antigens for CAR T-cell therapy in AML, which could help overcome challenges in treating CD19-negative myeloid malignancies and guide future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targets for chimeric antigen receptor T-cell therapy of acute myeloid leukemia. Schorr, C., Perna, F.[2023]

The study developed a novel CAR and secreted bi-specific T cell engager (sBite) targeting c-kit, a protein highly expressed in acute myeloid leukemia (AML), which is associated with poor prognosis and chemotherapy resistance.

Modified γδ T cells demonstrated the ability to kill c-kit+ AML cells in vitro and showed moderate survival benefits in mice with disseminated AML, although their effectiveness was limited by poor homing to the bone marrow, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia. Branella, GM., Lee, JY., Okalova, J., et al.[2023]

References

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

Current challenges for CAR T-cell therapy of acute myeloid leukemia. [2020]

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

Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. [2021]

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

CD38 as a pan-hematologic target for chimeric antigen receptor T cells. [2023]

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

Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. [2023]

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

Next generations of CAR-T cells - new therapeutic opportunities in hematology? [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Targets for chimeric antigen receptor T-cell therapy of acute myeloid leukemia. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia. [2023]