CD83 CAR T Cells for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: Glucocorticoids, Investigational therapies

Disqualifiers: APL, CNS leukemia, HIV, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with acute myeloid leukemia (AML) that hasn't responded to other treatments or has returned after remission. The treatment uses specially engineered cells, called CD83 CAR T cells (a type of immunotherapy), to target and destroy harmful leukemia cells. The goal is to determine the safety and effectiveness of this treatment. People with relapsed or treatment-resistant AML 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?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use systemic glucocorticoids above a certain dose or be on certain investigational therapies close to the time of treatment. It's best to discuss your specific medications with the trial team.

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

Research has shown that CD83 CAR T cells could be safe and manageable for people with acute myeloid leukemia (AML) that has returned or is difficult to treat. These cells are designed to target and destroy AML cells without harming healthy ones. In other studies on CAR T cell therapy for AML, patients have generally responded well to the treatment. Although reports of side effects exist, they are usually manageable. It is important to note that this is an early-stage trial, with the primary goal of assessing the treatment's safety. This stage focuses on understanding any side effects and determining the optimal dose. ^{1 2 3 4 5}

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

Researchers are excited about autologous Anti-CD83 CAR T-cells for acute myeloid leukemia because these engineered cells target the CD83 protein, which is overexpressed in certain leukemia cells. Unlike traditional chemotherapy options like cytarabine and daunorubicin, which can affect both healthy and cancerous cells, CD83 CAR T-cells are designed to hone in on cancer cells more precisely, potentially reducing collateral damage to healthy cells. This targeted approach not only offers hope for greater effectiveness but also aims to minimize side effects, making it a promising new option for patients with this condition.

What evidence suggests that CD83 CAR T cells might be an effective treatment for acute myeloid leukemia?

Research has shown that a new treatment using CD83 CAR T cells can effectively target and destroy AML (acute myeloid leukemia) cells. One study found that AML cells have a protein called CD83, and these special CAR T cells successfully killed leukemia cells in the lab. This trial will evaluate the effectiveness of CD83 CAR T cells in patients with AML. This treatment is promising because it aims to prevent two major problems with stem-cell transplants: graft versus host disease and relapse. Early results suggest that CD83 CAR T cells could be a safe and manageable treatment for patients with AML that has returned or is difficult to treat. Overall, these engineered cells offer new hope for attacking cancer cells while sparing healthy ones. ^{1 3 6 7 8}

Who Is on the Research Team?

Shernan G Holtan

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia (AML) that has returned after treatment or hasn't responded to previous treatments. Participants must have AML blasts with CD83 protein and meet other health criteria not specified here.

Inclusion Criteria

Creatinine clearance: ≥ 40 mL/min (Cockroft-Gault)

Total bilirubin: ≤ 2mg/dL except for patients with Gilbert's syndrome, hemolysis, or related to disease

AST and ALT < 3.0 x upper limit of normal (ULN)

Exclusion Criteria

Enrollment in another investigational therapy protocol within specific timeframe

Requirement for treatments other than specified agents

Unwilling or unable to follow protocol requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

1 visit (in-person)

Leukapheresis and Pre-treatment

Leukapheresis to obtain PBMCs for CD83 CAR T cell product manufacturing and optional hydroxyurea administration

3 weeks

1 visit (in-person)

Conditioning and Treatment

Patients receive fludarabine and cyclophosphamide followed by CD83 CAR T cells infusion

1 week

Daily visits (in-person) for 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 2 weeks for 2 months, then at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Anti-CD83 CAR T-cells

Trial Overview The trial tests genetically engineered cells called CD83 CAR T cells, aiming to treat relapsed/refractory AML safely. It includes determining the best dose while monitoring side effects using various medical procedures and imaging techniques.

How Is the Trial Designed?

Group I: Treatment (fludarabine, cyclophosphamide, CD83 CAR T-cells) Experimental Treatment 12 Interventions

Patients undergo leukapheresis to obtain PBMCs for CD83 CAR T-cell product manufacturing on day -21 and may receive hydroxyurea at the discretion of the treating physician on study. Patients then receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive CD83 CAR T-cells IV over 15 minutes on day 0. Patients also undergo ECHO and chest x-ray during screening, blood sample collection throughout the study, and CT and/or PET, as well as lumbar puncture as clinically indicated. In addition, patients may undergo bone marrow aspiration throughout the study.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

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]

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]

The study introduces a new third-generation CAR T-cell therapy (3G.CAR33-T) targeting CD33 for treating acute myeloid leukemia (AML), showing improved viability, proliferation, and cytotoxicity compared to second-generation CAR T-cells.

3G.CAR33-T cells effectively kill CD33-positive leukemia cells while sparing normal hematopoietic stem and progenitor cells, suggesting a safer treatment option that could be combined with genome-edited stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD33-directed immunotherapy with third-generation chimeric antigen receptor T cells and gemtuzumab ozogamicin in intact and CD33-edited acute myeloid leukemia and hematopoietic stem and progenitor cells. Liu, Y., Wang, S., Schubert, ML., et al.[2022]

A novel method was developed to generate large numbers of reactive T-cell lines specifically targeting acute myeloid leukemia (AML), with an estimated frequency of 6 AML-reactive T cells per million peripheral blood mononuclear cells from patients.

These T-cell lines demonstrated the ability to specifically kill autologous AML cells and induce apoptosis, particularly through CD4(+) T cells, suggesting their potential for effective adoptive immunotherapy in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of T-cell lines to autologous acute myeloid leukemia cells by competitive limiting dilution culture of acute myeloid leukemia mononuclear cells. Zhong, RK., Lane, TA., Ball, ED.[2008]

The compound CAR (cCAR) T-cell therapy, which targets both CD123 and CD33 antigens in acute myeloid leukemia (AML), demonstrated strong anti-tumor activity and improved survival in four different leukemia mouse models.

The inclusion of a safety-switch using alemtuzumab allows for the rapid termination of cCAR therapy if needed, enhancing the safety profile of this dual-targeting approach against AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. Petrov, JC., Wada, M., Pinz, KG., et al.[2021]

In a small trial, T cells modified to target the Wilms tumor antigen 1 were effective in preventing relapse in patients with acute myeloid leukemia after they underwent an allogeneic stem-cell transplant.

This approach highlights the potential of engineered T cell therapies in enhancing post-transplant outcomes for leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR Gene Therapy Improves AML Prognosis. [2020]

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]

In a study testing CD33-CAR NK cells in patients with relapsed and refractory acute myeloid leukemia (AML), no significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting a favorable safety profile.

CAR NK-92 cells can be produced at a lower cost than CAR T cells, indicating that with further optimization, they could become a more accessible treatment option for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Tang, X., Yang, L., Li, Z., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06871410

NCT06871410 | Genetically Engineered Cells (CD83 CAR ... Giving CD83 CAR T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML. Detailed Description. PRIMARY OBJECTIVE:.

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/581255

Genetically Engineered Cells (CD83 CAR T Cells) for the ... Giving CD83 CAR T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML. Read more ...

3. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-3-2025-127ec

CD83 CAR T Cells for Acute Myeloid Leukemia Therefore, human CD83 CAR T cells are a promising cell-based approach to preventing two critical complications of stem-cell transplant - GVHD and relapse.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7456225/

Human CD83-targeted chimeric antigen receptor T cells ... We show that human acute myeloid leukemia (AML) expresses CD83 and that myeloid leukemia cell lines are readily killed by CD83 CAR T cells. Human CD83 CAR T ...

5. cancer.gov cancer.gov/clinicaltrials/NCI-2025-01523

Genetically Engineered Cells (CD83 CAR T Cells) for the ... Giving CD83 CAR T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML. Eligibility Criteria ...

6. 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.

7. 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.

8. 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 We summarize here the findings, challenges, and new developments of CAR therapy for AML. These illustrate the need to specifically adapt CAR strategies to the ...