CAR T-Cell Therapy for Acute Myeloid Leukemia

Recruiting at 2 trial locations

Overseen By Swati Naik, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Systemic steroids, Rituximab

Disqualifiers: HIV, Severe infections, APL, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1-2 days

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CD123-CAR T-cell therapy, designed to help individuals with certain blood cancers, such as acute myeloid leukemia (AML) and similar conditions. The primary goal is to determine the safest dose of these specialized cells for patients while monitoring for side effects. Patients with these conditions who have struggled with previous treatments might be suitable candidates, particularly if their disease is CD123 positive, indicating the presence of specific markers targeted by this therapy. 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 new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before the CD123-CAR T-cell infusion. Specifically, you cannot be on systemic steroids exceeding a certain dose, systemic therapy that might interfere with the T cells, rituximab, or intrathecal chemotherapy within specified time frames before the infusion.

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

Research has shown that CD123-CAR T-cell therapy holds promise in early studies for treating acute myeloid leukemia (AML) and other blood cancers. Patients have generally tolerated this treatment well. In one study, some patients experienced side effects, but these were mostly mild and manageable.

CAR T-cell therapy, a type of immunotherapy, uses specially modified white blood cells to attack cancer cells. Although researchers are still studying this treatment, it has been used safely in other types of cancer.

In summary, while CD123-CAR T-cell therapy remains under investigation, early results suggest it is generally safe, with manageable side effects reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for acute myeloid leukemia, which often include chemotherapy and stem cell transplants, CD123-CAR T-cell therapy uses a different approach by harnessing the body's own immune cells. This therapy involves engineering T-cells to specifically target and destroy leukemia cells expressing the CD123 protein. Researchers are excited because this targeted action could mean fewer side effects and potentially more effective eradication of cancer cells, especially for patients who have relapsed or don't have a donor for a transplant. This innovative method offers hope for a more personalized and efficient treatment option.

What evidence suggests that CD123-CAR T-cell therapy might be an effective treatment for AML?

Research has shown that CD123-CAR T-cell therapy, which participants in this trial may receive, could be a promising treatment for acute myeloid leukemia (AML). This therapy targets a protein called CD123, often found on leukemia cells. By focusing on this protein, CD123-CAR T-cells can attack and destroy cancer cells. Early results indicate that this method has significantly reduced leukemia cells in some patients. Another study found that similar CAR T-cell therapies led to complete remission in many patients with other types of leukemia. While more research is needed, these early findings offer hope for its effectiveness in treating AML. ^{1 3 5 6 7}

Who Is on the Research Team?

Swati Naik, MD

Principal Investigator

St. Jude Children's Research Hospital

Paulina Velasquez, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young people (21 or younger) with certain types of leukemia that have come back or didn't respond to treatment. They should be in a condition where they can live at least 12 more weeks, able to do some daily activities, and not pregnant or breastfeeding. They must also have a donor ready for cell therapy.

Inclusion Criteria

Relapsed/refractory CD123+ disease defined as follows: AML/MDS - Relapsed disease: Patients developing recurrent disease after a first complete remission (CR) Refractory disease: Patients not achieving a CR after 2 cycles of induction chemotherapy B-cell ALL - Relapsed disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies including Patients in 2nd or greater relapse Patients with relapse after allogeneic HSCT Refractory disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies T-cell All - Relapsed refractory disease that is CD123 positive BPDCN - Relapsed/refractory disease that has failed front-line therapy Estimated life expectancy of >12 weeks Karnofsky or Lansky (age-dependent) performance score ≥50 Patients with a history of prior allogeneic HCT must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis Patient must have an identified, suitable HCT donor For females of child-bearing age: Not lactating with intent to breastfeed Not pregnant with negative serum pregnancy test within 7 days prior to enrollment Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis

I am 21 years old or younger.

Exclusion Criteria

You are expected to live for at least 8 more weeks.

My bilirubin levels are within normal range, except I have Gilbert's syndrome.

I have not received rituximab therapy in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Collection and Manufacturing

Blood cells are collected via apheresis and modified to improve their ability to recognize and kill cancer cells

2-3 weeks

Chemotherapy

Lymphodepleting chemotherapy is administered to prepare the body for CD123-CAR T cell infusion

4 days

Daily visits for chemotherapy administration

Treatment

Infusion of CD123-CAR T cells following chemotherapy

1-2 days

1 visit for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CD123-CAR T
• Cyclophosphamide
• Fludarabine
• Rituximab

Trial Overview The trial tests CD123-CAR T-cell therapy after chemotherapy to find the highest safe dose. It's given through an IV and aims to see how well it works against leukemia and what side effects it has on patients' bodies, disease control, and survival rates.

How Is the Trial Designed?

Group I: ARM B CD123-CAR T cell therapy Experimental Treatment 5 Interventions

For patients who relapsed following allogeneic transplant and whose CAR T-cells will be manufactured from the previous transplant donor, when available. CD123-CAR T-cell dose and infusion Up to 4 Dose levels will be evaluated with a maximum dose of 2.5 x 10\^8 CAR+ T cells. If dose limiting toxicities (DLTs) are observed on Dose level 1 then the cell dose is de- escalated.

Group II: ARM A CD123-CAR T cell therapy Experimental Treatment 5 Interventions

For patients who have not received an allogeneic transplant or for patients who have received allogeneic transplant and do not have a transplant donor available CD123-CAR T-cell dose and infusion Up to 4 Dose levels will be evaluated with a maximum dose of 2.5 x 10\^8 CAR+ T cells. If dose limiting toxicities (DLTs) are observed on Dose level 1 then the cell dose is de- escalated.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

The study developed a new type of T cell, called CD123-CAR-VST, which can target both acute myeloid leukemia (AML) cells and viral infections like EBV, adenovirus, and CMV, potentially addressing two major complications after hematopoietic stem cell transplantation (HSCT).

CD123-CAR-VST cells were shown to effectively recognize and attack both AML cells and viral antigens in laboratory tests, suggesting they could be a promising treatment option for preventing relapse and viral infections in patients who have undergone HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD123 redirected multiple virus-specific T cells for acute myeloid leukemia. Zhou, L., Liu, X., Wang, X., et al.[2016]

Modified Vγ9Vδ2 T cells expressing anti-CD123 CAR showed significantly improved ability to kill acute myeloid leukemia (AML) cells in laboratory tests, indicating their potential effectiveness as a treatment.

In a mouse model of AML, these modified T cells demonstrated enhanced tumor control, suggesting they could be a promising alternative therapy for patients with this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of Vγ9Vδ2 T cells. Zhang, X., Ang, WX., Du, Z., et al.[2022]

The UniCAR-T platform, designed to target CD123, effectively eliminated CD123+ leukemia cells in both laboratory and animal models, demonstrating strong anti-leukemic efficacy.

This innovative CAR-T approach includes a safety-switch mechanism that allows for controllable toxicity, reducing the risk of harm to healthy hematopoietic cells, which is a significant improvement over traditional CD123 CAR-T therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapidly Switchable Universal CAR-T Cells for Treatment of CD123-Positive Leukemia. Loff, S., Dietrich, J., Meyer, JE., et al.[2020]

CD123 chimeric antigen receptor (CAR) redirected T cells have shown strong antileukemic activity, indicating a promising new approach for treating acute myeloid leukemia.

The development of CD123 CARs provides insights into enhancing immunotherapy strategies, highlighting the need for novel treatments in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia therapeutics: CARs in the driver's seat. Mardiros, A., Brown, CE., Budde, LE., et al.[2021]

CD123 CAR T cells, designed to target the interleukin-3 receptor α chain (CD123) overexpressed in acute myeloid leukemia (AML), showed strong effectiveness against AML cell lines and primary patient samples, indicating their potential as a powerful immunotherapy.

These CAR T cells did not harm normal blood cell formation in vitro and demonstrated the ability to kill AML cells from patients, suggesting a targeted approach that minimizes damage to healthy cells while effectively treating high-risk AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Mardiros, A., Dos Santos, C., McDonald, T., et al.[2023]

CD123 is identified as a promising target for CAR T-cell therapy in acute myeloid leukemia (AML), as its expression increases over time in tumor cells, making it a viable option for treatment.

While CART123 T cells effectively eliminate AML cells in mice, they also destroy normal blood cell production, highlighting the need for careful management and potential rescue strategies during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Gill, S., Tasian, SK., Ruella, M., 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]

CD123 is a promising target for CAR T-cell therapy in leukemia because it is highly expressed in leukemic stem cells while being minimally present in normal blood stem cells, which may reduce potential side effects.

Preclinical studies indicate that CD123 CAR T cells show strong anti-leukemic effects, making them a potential effective treatment option for patients with relapsed or refractory acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells expressing CD123 chimeric antigen receptors for treatment of acute myeloid leukemia. Mardiros, A., Forman, SJ., Budde, LE.[2018]

CAR-modified T cells, specifically those expressing anti-CD123, have shown effectiveness in treating Acute Myeloid Leukemia (AML) by eradicating AML cells.

This innovative immunotherapeutic approach highlights the potential of genetically modified T cells as a promising strategy in the development of AML treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD123 AML targeting by chimeric antigen receptors: A novel magic bullet for AML therapeutics? Tettamanti, S., Biondi, A., Biagi, E., et al.[2022]

Engineered CAR T cells targeting CD123, which is overexpressed in acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL), show promise in treating these cancers while minimizing damage to normal hematopoietic stem cells.

The study demonstrated that a specific combination of antibody chains in CAR T cells can maintain anti-tumor activity without significantly harming normal cells, suggesting a safer approach for immunotherapy in hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors. Thokala, R., Olivares, S., Mi, T., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11938459/

Recent advances of CAR-T cells in acute myeloid leukemia This review mainly summarizes and discusses the research progress and the clinical application of CAR-T cell immunotherapy in AML in recent years.

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

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02623582

NCT02623582 | CD123 Redirected Autologous T Cells for ... Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing anti-CD ...

4. 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.

5. 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 single CD19 CAR T-cell infusion yields a complete remission (CR) in 80% of patients with B-ALL, approximately half of whom will be alive after ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11141645/

Chimeric antigen receptor T-cell therapy in childhood acute ... Here we review the results of early phase clinical studies with AML-specific CAR T cells, and avenues investigators are exploring to improve their effector ...

7. cell.com cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(25)00261-8

CAR-T cell therapy for treatment of acute myeloid leukemia ... This trial served as a feasibility and safety record of CAR-T cell therapy in AML patients. Anti-CD123 CAR. The cell-surface marker CD123 has ...