CAR T Cell Therapy for Acute Myeloid Leukemia

Recruiting at 6 trial locations

Overseen By Jae Park, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, HIV, HBV, HCV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 6 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new treatment, CD371-YSNVZ-IL18 CAR T cells (a type of cell therapy), is safe for individuals with acute myeloid leukemia (AML). Researchers are testing different doses to identify the most effective one with the fewest side effects. The trial seeks participants whose AML has returned after treatment or has not responded to other treatments. Participants should have a history of AML and may have already tried other treatments without success. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that CD371-YSNVZ-IL18 CAR T cells are likely to be safe for humans?

Research shows that CD371-YSNVZ-IL18 CAR T cells have been tested in a small group of people. In one study, five patients with relapsed acute myeloid leukemia received this treatment. The results indicated that the treatment was generally safe, although some patients experienced mostly mild side effects.

These studies are in the early stages, focusing on safety and determining the right dose. While some evidence suggests the treatment is generally safe, more research is needed to fully understand the risks. Since this treatment is still under investigation and not yet approved by the FDA for treating leukemia, prospective participants should consider this when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Researchers are excited about CD371-YSNVZ-IL18 CAR T cells because they offer a new way to tackle acute myeloid leukemia (AML), especially in patients whose cancer has relapsed or resisted other treatments. Unlike traditional chemotherapy, which attacks cancer cells broadly, this CAR T-cell therapy targets the CD371 protein, found specifically on leukemia cells, offering a more precise attack. Additionally, these engineered T cells include a component that boosts immune response (IL18), potentially improving their effectiveness and durability. This innovative approach not only aims to improve outcomes but also to reduce the side effects commonly associated with broader treatments.

What evidence suggests that CD371-YSNVZ-IL18 CAR T cells might be an effective treatment for acute myeloid leukemia?

Research has shown that a new treatment, CD371-YSNVZ-IL18 CAR T cells, is under study for its potential to treat acute myeloid leukemia (AML) in this trial. While CAR T-cell therapy has proven effective for some blood cancers, it has not yet achieved the same success for AML. Participants in this trial will receive varying doses of CD371-YSNVZ-IL18 CAR T cells, which are engineered to target and attack a protein on AML cells, potentially enhancing the immune system's ability to fight the cancer. Early results suggest that these modified cells can boost the immune response due to the inclusion of interleukin-18, a molecule that enhances immune activity. Although solid evidence on the effectiveness of these specific CAR T cells for AML is limited, their design is based on successful strategies used in other cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Mark Geyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CD371-YSNVZ-IL18 CAR T cells

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Current treatments for acute myeloid leukemia (AML) often fail or lead to relapses, highlighting the need for new therapeutic strategies.

Chimeric antigen receptor (CAR) T cell therapy, which has shown success in treating B-lineage cancers, is being explored for AML, with ongoing research into potential surface markers and strategies to improve its effectiveness in this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. Fan, M., Li, M., Gao, L., et al.[2021]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40864984/

CD371-Targeted CAR T cells Secreting Interleukin-18 ... Success of chimeric antigen receptor (CAR) T-cell therapy in lymphoid malignancies has not yet been recapitulated in acute myeloid leukemia (AML) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06017258

A Study of CD371-YSNVZIL-18 CAR T Cells in People With ... The purpose of this study is to find out whether CD371-YSNVZ-IL18 CAR T cells are safe, and to look for the highest dose of CD371-YSNVZ-IL18 CAR T cells ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2023-06968

A Study of CD371-specific/YSNVz/IL-18 CAR T Cells in ... This phase I trial tests the safety, side effects, best dose, and effectiveness of CD371-specific/YSNVz/IL-18 chimeric antigen receptor (CAR) T cells in ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/420095

A Study of CD371-YSNVZIL-18 CAR T Cells in People With ... The purpose of this study is to find out whether CD371-YSNVZ-IL18 CAR T cells are safe, and to look for the highest dose of CD371-YSNVZ-IL18 ...

5. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper194162.html

Paper: CD371-Targeted CAR T-Cells Secreting Interleukin ... OffLabel Disclosure: CD371-SAVVYz-IL18 CAR T-cells are not FDA-approved for treatment of acute myeloid leukemia. See more of: 704. Cellular ...