Anti-FLT3 CAR-T Cells for AML

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Hemogenyx Pharmaceuticals LLC

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pregnancy, Active malignancy, Hepatitis, others

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

Compensation: Varies

Number of Visits: 14

Duration: 4 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called anti-FLT3 CAR-T cells, a type of immunotherapy, to determine its safety for people with a challenging type of blood cancer known as AML (acute myeloid leukemia). The study will evaluate the treatment's effectiveness and the duration of any benefits. Ideal candidates for the trial are those with AML that has not responded to other treatments or has recurred, particularly if the cancer cells have a marker called FLT3. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are using certain immunosuppressant medications or high doses of systemic steroids.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Earlier studies have examined anti-FLT3 CAR-T cell therapy for treating acute myeloid leukemia (AML), focusing primarily on its safety and effectiveness. Research has shown that CAR-T cell therapies can cause side effects such as cytokine release syndrome, a strong immune reaction, and neurotoxicity, which is nerve damage. However, medical care can often manage these side effects.

As a phase 1 study, this trial's main goal is to assess the treatment's safety. Phase 1 trials typically involve fewer participants and concentrate on identifying any serious side effects. The aim is to determine the optimal dose that balances effectiveness and safety. This trial tests different dose levels to ensure safety across various dosages.

If anti-FLT3 CAR-T cells had already been approved for another condition, it might suggest a higher safety profile. However, since this is an early phase trial specifically for AML, participants should understand that the primary focus is on safety assessment. Open discussions with the study team about any concerns are important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Researchers are excited about Anti-FLT3 CAR-T cells because they offer a novel approach for treating acute myeloid leukemia (AML). Unlike traditional treatments like chemotherapy and stem cell transplants, which can be broad and affect healthy cells, Anti-FLT3 CAR-T cells are designed to specifically target and eliminate cancer cells with the FLT3 mutation. This precision could potentially lead to more effective outcomes and fewer side effects. Additionally, CAR-T cell therapy harnesses the body’s own immune system to fight cancer, which is a groundbreaking step forward in personalized medicine for AML.

What evidence suggests that anti-FLT3 CAR-T cells might be an effective treatment for AML?

Research has shown that a new treatment using anti-FLT3 CAR-T cells may help treat acute myeloid leukemia (AML). Studies have found that this therapy can lead to high rates of complete remission, meaning the cancer becomes undetectable. For instance, some trials reported that about 72% of patients went into remission just 14 days after receiving the treatment. However, the challenge remains with long-term survival, as some studies found that only about 30% of AML patients survive for five years after treatment. This trial will explore different dose levels of anti-FLT3 CAR-T cells to evaluate their effectiveness and safety. These early findings suggest that anti-FLT3 CAR-T cells could be effective against AML, but more research is needed to understand their long-term benefits. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with relapsed or refractory Acute Myeloid Leukemia (AML), including childhood cancer and granulocytic leukemia. Participants must have previously received treatments that are no longer effective.

Inclusion Criteria

Subjects must have a suitable stem cell transplant donor

I had a transplant, am not on immunosuppressants for 1 month, and have no GvHD needing them.

I am fully active or can carry out light work.

Exclusion Criteria

I had a stem cell transplant from a donor under specific conditions.

I do not have active hepatitis B, hepatitis C, or HIV.

Known history of allergy or hypersensitivity to study product excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of HG-CT-1 CAR-T cells, with dose escalation to determine safety

4 weeks

Multiple visits for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose-limiting toxicities and clinical response

12 months

Regular visits at Day 14, Day 28, Month 3, Month 6, and Month 12

What Are the Treatments Tested in This Trial?

Interventions

• Anti-FLT3 CAR-T cells

Trial Overview The study tests a new therapy called Anti-FLT3 CAR-T cells, aiming to determine its safety at different doses in up to 18 subjects who will receive an infusion of HG-CT-1, the study drug.

How Is the Trial Designed?

Group I: Dose level 3: 3.5x10^8 Transduced CAR+ HG-CT-1 Experimental Treatment 1 Intervention

Group II: Dose level 2: 1.4x10^8 Transduced CAR+ HG-CT-1 Experimental Treatment 1 Intervention

Group III: Dose level 1: 7x10^7 Transduced CAR+ HG-CT-1 Experimental Treatment 1 Intervention

Group IV: Dose level -1: 3.5 x 10^7 Transduced CAR+ HG-CT-1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Hemogenyx Pharmaceuticals LLC

Lead Sponsor

Trials

1

Recruited

20+

MD Anderson Cancer Center University of Texas

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Monovalent FLT3-targeted CAR T cells (FLT3CART) and bispecific CD19xFLT3CART show strong anti-leukemia activity in preclinical models of FLT3-mutant acute myeloid leukemia (AML) and KMT2A-rearranged acute lymphoblastic leukemia (ALL), indicating their potential as effective treatments.

These CAR T-cell therapies demonstrated minimal cross-reactivity with normal tissues and significant in vivo inhibition of leukemia proliferation, suggesting a promising safety profile and efficacy for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against FLT3- mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia. Niswander, LM., Graff, ZT., Chien, CD., et al.[2023]

The study developed a chimeric antigen receptor (CAR) targeting the Flt3 tyrosine kinase, which is associated with poor outcomes in acute myeloid leukemia (AML), demonstrating specific killing of Flt3-positive cancer cells without harming Flt3-negative cells.

Flt3-CAR T cells showed strong antitumor effects in vitro and low off-target cytotoxicity, suggesting a promising new approach for treating relapsed/refractory AML with potentially fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural Flt3Lg-Based Chimeric Antigen Receptor (Flt3-CAR) T Cells Successfully Target Flt3 on AML Cell Lines. Maiorova, V., Mollaev, MD., Vikhreva, P., et al.[2021]

Anti-FLT3 CAR T-cell therapies are being developed as a promising treatment for acute myeloid leukemia (AML), especially for patients with limited options after relapse, showing effectiveness in both laboratory and animal studies.

While these therapies demonstrate potential efficacy, their safety profiles require further investigation, and initial clinical trials have begun to assess their effectiveness in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Development of Anti-FLT3 CAR T-Cell Therapies for Treatment of AML. Pedersen, MG., Møller, BK., Bak, RO.[2022]

AMG 553, a CAR T-cell therapy targeting FLT3, shows promise in selectively targeting acute myeloid leukemia (AML) cells while demonstrating limited toxicity to healthy cells, based on studies in cynomolgus monkeys.

Nonclinical safety assessments indicate that while AMG 553 effectively targets FLT3-positive AML cells, it may also affect some normal hematopoietic stem and progenitor cells, suggesting a need for careful monitoring in clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical Safety Assessment of AMG 553, an Investigational Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Acute Myeloid Leukemia. Karbowski, C., Goldstein, R., Frank, B., et al.[2021]

FLT3 is a key receptor involved in the survival and proliferation of blood cells, and its mutations are linked to poor outcomes in acute myeloid leukemia (AML), making it a critical target for treatment.

Several small molecule tyrosine kinase inhibitors (TKIs) targeting FLT3 have shown promise in early clinical trials, particularly when combined with traditional chemotherapy, indicating a potential strategy for improving responses in patients with FLT3-mutant AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting FLT3 for the treatment of leukemia. Small, D.[2021]

The study presents a promising off-the-shelf CAR T cell therapy targeting FLT3 for treating acute myeloid leukemia (AML), showing effective elimination of AML cells in preclinical models.

While the therapy demonstrated strong efficacy, it also posed a risk of myelotoxicity by affecting healthy hematopoietic stem cells; however, a rituximab-responsive off-switch was developed to allow for safe depletion of CAR T cells after treatment, enabling bone marrow recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic FLT3 CAR T Cells with an Off-Switch Exhibit Potent Activity against AML and Can Be Depleted to Expedite Bone Marrow Recovery. Sommer, C., Cheng, HY., Nguyen, D., et al.[2021]

Engineered T-cells targeting FLT3 show strong effectiveness against acute myeloid leukemia (AML) cells, including those with the FLT3-ITD mutation, indicating a promising new treatment approach for high-risk AML patients.

Combining FLT3-CAR T-cell therapy with the FLT3-inhibitor crenolanib enhances the recognition and destruction of AML cells, suggesting a synergistic effect that could improve treatment outcomes, although caution is needed due to potential damage to normal hematopoietic stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib. Jetani, H., Garcia-Cadenas, I., Nerreter, T., et al.[2019]

Dual-target FLT3scFv/NKG2D-CAR T cells effectively kill acute myeloid leukaemia (AML) cells in both laboratory tests and in a mouse model, showing promise as a treatment option.

The FLT3 inhibitor gilteritinib enhances the effectiveness of these CAR T cells by increasing the expression of NKG2D ligands on AML cells through the NF-κB2 signaling pathway, suggesting a synergistic approach to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel approach for relapsed/refractory FLT3mut+ acute myeloid leukaemia: synergistic effect of the combination of bispecific FLT3scFv/NKG2D-CAR T cells and gilteritinib. Li, KX., Wu, HY., Pan, WY., et al.[2022]

FLT3L CAR-T cells specifically target and kill FLT3+ leukemia cells, including those with the FLT3-ITD mutation, showing strong potential for treating acute myeloid leukemia (AML).

In mouse models, FLT3L CAR-T therapy significantly prolonged survival without harming normal hematopoietic stem cells, indicating a promising safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. Wang, Y., Xu, Y., Li, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9598885/

Recent Advances in the Development of Anti-FLT3 CAR T ... Although there is a relatively high complete remission rate, the 5-year overall survival is approximately 30% because one third of AML patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625002618

CAR-T cell therapy for treatment of acute myeloid leukemia ... This review discusses the advances of CAR-T cell therapy in AML, targets, and outcomes in preclinical and clinical studies.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06786533

NCT06786533 | Clinical Study of Anti-FLT3 CAR-T Cells ... This is a phase 1 dose escalation study to determine the safety of anti-FLT3 CAR-T in subjects with R/R AML. The primary objective is to assess safety.

4. ashpublications.org ashpublications.org/blood/article/145/11/1113/534311/Honing-CAR-T-cells-to-tackle-acute-myeloid

Honing CAR T cells to tackle acute myeloid leukemia | Blood A cohort of 32 pediatric and adult patients with AML treated with CLEC12A CAR T cells showed 72% CR 14 days after CAR therapy. Up to 59% of ...

5. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... There is currently no standardized treatment protocol for these patients, and the 5-year overall survival (OS) rate is below 20%. Therefore, R/R ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.7032

Nonclinical safety assessment of AMG 553, an ... All findings in toxicology studies with anti-FLT3 BiTEs were consistent with the targeted killing of cells expressing FLT3 on the plasma ...