CAR T Cell Therapy for Acute Myeloid Leukemia

Overseen By Katherine G. Tarlock, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Anticancer agents, Steroids, TKIs, others

Disqualifiers: Active malignancy, CNS disease, Severe infection, others

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

Compensation: Varies

Number of Visits: 3

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and proper dosage of a new treatment using modified T cells to combat acute myeloid leukemia (AML) in children, particularly those whose cancer has returned or did not respond to earlier treatments. The treatment, known as FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy, involves altering a patient's own T cells in a lab to better target and destroy cancer cells. Children with AML that shows a specific marker (FOLR1) and have had issues with previous treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications before joining the trial. Chemotherapy and biologic agents must be stopped at least 14 days before enrollment, corticosteroids at least 7 days before, tyrosine kinase inhibitors 3 days before, and hydroxyurea 1 day before. FOLR1 targeting therapy must be stopped 30 days before enrollment.

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

Research shows that FH-FOLR1 CAR T cell therapy is being tested for safety and patient tolerance. CAR T cell therapy involves modifying a patient's immune cells to enhance their ability to fight cancer. Previous studies have demonstrated that this treatment can be highly effective against cancer.

As this trial is in its early stages, it primarily focuses on assessing the safety of this treatment for children with a type of leukemia that hasn't responded to other treatments or has recurred. Although detailed safety data from previous studies on this specific treatment isn't available, testing in humans suggests some confidence in its potential safety and effectiveness.

Patients typically receive chemotherapy drugs, such as fludarabine and cyclophosphamide, before receiving the CAR T cells. These drugs enhance the effectiveness of the CAR T cells. Side effects can occur, but the trial aims to determine the safest and most effective dose. This trial will provide valuable information on patient tolerance and any side effects experienced. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy options for acute myeloid leukemia, such as cytarabine and daunorubicin, FH-FOLR1 CAR T therapy works by engineering a patient's own T cells to specifically target and attack cancer cells. This treatment is unique because it uses a chimeric antigen receptor (CAR) to direct the T cells against a protein called FOLR1 found on the surface of leukemia cells. Researchers are excited about this approach because it offers a more personalized and potentially powerful way to eliminate cancer cells, harnessing the body's immune system to do so with precision. This could lead to more effective and longer-lasting remissions compared to traditional therapies.

What evidence suggests that FH-FOLR1 CAR T cell therapy might be an effective treatment for acute myeloid leukemia?

Research has shown that FH-FOLR1 CAR T Cell Therapy, which participants in this trial will receive, could be promising for treating acute myeloid leukemia (AML) by targeting specific cancer cells. In early lab studies, this treatment demonstrated a strong ability to fight tumors, effectively attacking cancer cells in both small and large areas. This therapy modifies a patient's T cells (a type of immune cell) to help them find and destroy cancer cells more effectively. The goal is for these modified T cells to better target leukemia cells, potentially leading to improved treatment results. While the exact effectiveness in humans remains under study, early findings are encouraging. ^{1 2 5 6 7}

Who Is on the Research Team?

Katherine G. Tarlock, MD

Principal Investigator

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for pediatric patients with a type of blood cancer called acute myeloid leukemia (AML) that has either returned after treatment or hasn't responded to previous treatments. Specific details on eligibility criteria are not provided, but typically include factors like age range, health status, and the presence of FOLR1+ AML.

Inclusion Criteria

Laboratory and meets one of the specified definitions

Has an appropriate stem cell donor source identified

I can undergo a procedure to collect my blood cells.

Exclusion Criteria

I have active graft-versus-host disease or received treatment for it within the last 4 weeks.

I am currently fighting a severe infection.

I have a history of brain or spinal cord disease that needed treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Apheresis

Patients undergo apheresis to obtain T cells for product manufacturing

1 week

1 visit (in-person)

Lymphodepleting Chemotherapy

Patients receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide

4 days

Daily visits (in-person)

CAR T Cell Infusion

Patients receive FH-FOLR1 CAR T cells infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Regular visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy

Trial Overview The trial is testing FH-FOLR1 CAR T-cell therapy in children with AML. It involves modifying the patient's immune cells to target cancer cells and giving chemotherapy drugs before infusing these engineered cells back into the patient to see if it's safe and works against AML.

How Is the Trial Designed?

Group I: Treatment (FH-FOLR1 CAR T) Experimental Treatment 9 Interventions

Patients undergo apheresis to obtain T cells for product manufacturing. Patients receive lymphodepleting chemotherapy with fludarabine IV on days -4 to -1 and cyclophosphamide IV on days -4 and -3. Patients receive FH-FOLR1 CAR T IV on day 0. Patients undergo ECHO at screening, undergo collection of CSF and blood samples and bone marrow aspiration/biopsy throughout the study, and may undergo PET scan on study and during follow up.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Kuni Foundation

Collaborator

Trials

3

Recruited

270+

Published Research Related to This Trial

The study developed the first chimeric antigen receptors (CARs) targeting folate receptor β (FRβ), which is present in 70% of acute myeloid leukemia (AML) cases, showing effective activation and killing of AML cells in both lab and mouse models.

Importantly, m909 CAR T cells did not harm healthy hematopoietic stem and progenitor cells, indicating a potential for safe application in treating AML, especially when combined with all-trans retinoic acid (ATRA) to enhance FRβ expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of folate receptor β on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells. Lynn, RC., Poussin, M., Kalota, A., et al.[2023]

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]

A novel T-cell immunotherapy was developed using a transgene that includes a T-cell receptor (TCR) specific for the HA-1 minor H antigen, which is associated with leukemia, aiming to target and eliminate leukemia cells after hematopoietic stem cell transplantation (HCT).

This engineered T-cell product incorporates safety features, such as an inducible caspase 9 switch to remove T-cells if they cause toxicity, and is designed to enhance the persistence and function of T-cells while minimizing the risk of alloreactivity, showing promising functional responses against primary leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of T-cell immunotherapy for hematopoietic stem cell transplantation recipients at risk of leukemia relapse. Dossa, RG., Cunningham, T., Sommermeyer, D., et al.[2022]

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 new AbTCR-CSR platform targets two antigens, Wilms tumor 1 protein (WT1) and CD33, which are both highly expressed on acute myeloid leukemia (AML) cells, allowing for specific T-cell cytotoxicity while sparing healthy cells.

This dual targeting approach aims to enhance the efficacy of CAR T-cell therapy in AML by reducing toxicity and improving specificity, potentially leading to better clinical outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-receptor T cell platform with Ab-TCR and costimulatory receptor achieves specificity and potency against AML. Dao, T., Xiong, G., Mun, SS., et al.[2023]

Chimeric antigen receptor (CAR) T cell therapy has shown promising results in treating acute lymphoblastic leukemia, with high rates of complete and prolonged clinical responses, indicating its potential as a powerful treatment option.

CAR T cells work by specifically targeting tumor-associated antigens, acting as a 'living drug' that can provide long-term anti-tumor memory, although there are specific but manageable adverse events associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for acute leukemia: New insights in chimeric antigen receptors. Heiblig, M., Elhamri, M., Michallet, M., et al.[2020]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

CD93 has been identified as a promising target antigen for chimeric antigen receptor T-cell therapy in treating acute myeloid leukemia (AML).

The study also presents a strategy to reduce the risk of 'on-target/off-cancer toxicity,' which is a significant concern in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Employing Synthetic T-cell Biology to Target AML without On-Target/Off-Cancer Toxicity. Velasquez, MP., Gottschalk, S.[2023]

A novel second-generation chimeric antigen receptor (CAR) targeting CD33 has been developed, showing effectiveness in redirecting T cells to kill acute myeloid leukemia (AML) cells, which express CD33 in about 90% of cases.

In pre-clinical studies, this CAR therapy demonstrated significant anti-leukemia effects both in vitro and in vivo, effectively preventing leukemia development and delaying disease progression in mice, supporting its potential as a clinical treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. O'Hear, C., Heiber, JF., Schubert, I., et al.[2021]

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]

Chimeric antigen receptor (CAR) T cells targeting both CD123 and CD33, in addition to CLL-1, showed improved anti-tumor activity against acute myeloid leukemia (AML) cells, especially when the target cells expressed low levels of these antigens.

The study demonstrated that dual targeting led to enhanced T cell activation and better tumor control in vivo, resulting in improved survival rates in animal models without any antigen escape in residual tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinatorial antigen targeting strategies for acute leukemia: application in myeloid malignancy. Atilla, PA., McKenna, MK., Watanabe, N., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06609928

NCT06609928 | FH-FOLR1 Chimeric Antigen Receptor T ... This phase I trial tests the safety, side effects, and best dose of FH-FOLR1 chimeric antigen receptor (CAR) T cells in treating pediatric patients with ...

2. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_15172.fh-folr1-chimeric-antigen-receptor-t-cell-therapy-for-treating-pediatric-patients-with-relapsed-or-refractory-acute-myeloid-leukemia.html

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for ... The trial is evaluating if giving FH-FOLR1 CAR T cell therapy is safe and tolerable for pediatric patients with recurrent or refractory AML.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40919994/

Preclinical Evaluation of Folate Receptor-α Chimeric Antigen ... More importantly, FH FOLR1-CART demonstrates potent antitumor activity in both localized and metastatic in vivo cell-derived and patient-derived ...

4. withpower.com withpower.com/trial/phase-1-recurrent-childhood-acute-myeloid-leukemia-1-2025-23b6b

CAR T Cell Therapy for Acute Myeloid Leukemia FH-FOLR1 CAR T Cell Therapy is unique because it uses genetically engineered T cells to specifically target leukemia cells, potentially improving outcomes for ...

5. app.trialscreen.org app.trialscreen.org/trials/phase-1-fh-folr1-chimeric-antigen-receptor-t-cell-therapy-treating-pediatric-trial-nct06609928

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for ... Testing a new immunotherapy approach for treating children with acute myeloid leukemia that has relapsed or not responded to previous treatment. Check your ...

6. trialx.com trialx.com/clinical-trials/listings/322327/fh-folr1-chimeric-antigen-receptor-t-cell-therapy-for-treating-pediatric-patients-with-relapsed-or-refractory-acute-myeloid-leukemia/

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for ... The trial is evaluating if giving FH-FOLR1 CAR T cell therapy is safe and tolerable for pediatric patients with recurrent or refractory AML.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12455178/

Preclinical Evaluation of Folate Receptor-α Chimeric ... More importantly, FH FOLR1-CART demonstrates potent antitumor activity in both localized and metastatic in vivo cell-derived and patient-derived ...