CD4CAR for AML

Recruiting at 3 trial locations

Overseen By Huda S. Salman

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Huda Salman

Must not be taking: Systemic glucocorticoids, Gene therapy

Disqualifiers: CD4 negative AML, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CD4CAR, a type of engineered T-cell therapy, for individuals with acute myeloid leukemia (AML) that has returned or not responded to other treatments. The main goal is to determine if CD4CAR is safe and can help eliminate remaining cancer cells, facilitating a later stem cell transplant. This trial suits those with CD4-positive AML who have not succeeded with initial treatments. Participants should have previously undergone AML treatments and still have CD4-positive cancer that is unresponsive to other options. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot use high doses of systemic glucocorticoids (steroids) unless they can be safely reduced. You can continue low-dose steroids and inhaled glucocorticoids.

Is there any evidence suggesting that CD4CAR is likely to be safe for humans?

Research shows that CD4CAR T-cell therapy is still in early testing for treating acute myeloid leukemia (AML). Previous studies have found that CAR-T cell therapies can sometimes present safety challenges. For example, patients might experience side effects like cytokine release syndrome, where the immune system overreacts, or neurotoxicity, which involves nerve damage. However, healthcare teams closely monitor and manage these effects.

Since this treatment is in an early testing phase, the main goal is to understand its safety and patient tolerance. This stage helps researchers identify possible side effects and determine the right dose. While similar therapies have been used for other types of leukemia, CD4CAR specifically for AML is still under study for its safety.

Prospective trial participants should discuss potential risks and benefits with their healthcare provider to make an informed decision about participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD4CAR because it uses a novel approach to tackle acute myeloid leukemia (AML). Unlike traditional treatments, such as chemotherapy and targeted therapies, CD4CAR involves reprogramming a patient's own T cells with the anti-CD4 lentiviral vector to specifically target and destroy cancer cells. This method not only aims to enhance the precision of the attack on cancer cells but also has the potential to reduce collateral damage to healthy cells, which is a common issue with conventional treatments. By harnessing the body’s immune system, CD4CAR offers a promising new avenue for more effective and personalized AML treatment.

What evidence suggests that CD4CAR might be an effective treatment for AML?

Research has shown that CD4CAR T-cells, which participants in this trial will receive, could help treat acute myeloid leukemia (AML). These special immune cells are modified to find and attack cancer cells. In past studies, CAR-T cell therapies reduced cancer cells in some people with blood cancers. Early results suggest that these modified cells can shrink tumors and improve patient health. Although still in early stages, CD4CAR has the potential to aid those with recurrent or hard-to-treat AML. ^{1 2 3 4 6}

Who Is on the Research Team?

Huda Salman, MD, PhD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for individuals with Acute Myeloid Leukemia (AML) that has come back or hasn't responded to treatment. It's aimed at those who might be candidates for a stem cell transplant if this therapy reduces their disease.

Inclusion Criteria

I can undergo apheresis with no issues.

My lung function test shows a capacity of 60% or more.

My AML is resistant or has come back after initial treatment.

Exclusion Criteria

Active autoimmune diseases requiring systematic treatments

Eligibility for CD4CAR infusion: Afebrile and not receiving antipyretics, and no evidence of active infection. Negative pregnancy testing (if applicable). If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion. Planned infusion dose was successfully manufactured and met release criteria

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Qualifying subjects will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for the manufacturing of CD4CAR T-cells.

4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy to reduce tumor burden before CD4CAR infusion.

1-2 weeks

Treatment

Participants receive CD4CAR cells by infusion on Day 0 of treatment. Post-infusion monitoring includes blood draws for cytokine levels and CD4CAR Transgene Copy Number.

4 weeks

Visits on days 0, 1, 3, 5, 7, 14, and 28

Follow-up

Participants are monitored for safety and effectiveness after treatment, with clinicoradiologic measurements of residual tumor burden and quarterly clinical evaluations.

2 years

Monthly for 6 months, then quarterly

Long-term Follow-up

Participants enter a rollover study to assess for disease-free survival (DFS), relapse, and development of other health problems or malignancies.

13 years

Twice a year by phone and questionnaire

What Are the Treatments Tested in This Trial?

Interventions

• CD4CAR

Trial Overview The study tests CD4CAR, a type of engineered T-cell therapy designed to target AML cells. This Phase I trial will assess the safety and potential effectiveness of CD4CAR as a preparatory step before a stem cell transplant.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Redirected autologous T cells transduced with the anti-CD4 lentiviral vector (referred to as "CD4CAR" cells)

CD4CAR is already approved in United States for the following indications:

Approved in United States as CD4CAR for:

• Relapsed or refractory T-cell leukemia and lymphoma

Who Is Running the Clinical Trial?

Huda Salman

Lead Sponsor

Trials

3

Recruited

80+

iCell Gene Therapeutics

Industry Sponsor

Trials

15

Recruited

270+

Published Research Related to This Trial

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-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]

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 study demonstrates the successful engineering of cytokine-induced killer (CIK) cells with a CD33 chimeric antigen receptor (CAR) using an optimized non-viral transposon system, which enhances CAR expression and reduces DNA transposase requirements.

CD33.CAR-CIK cells showed significant anti-leukemic effects in both in vitro and in vivo models, effectively targeting chemotherapy-resistant acute myeloid leukemia (AML) cells, indicating their potential for integration into existing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD33 in Chemoresistant AML Patient-Derived Xenografts by CAR-CIK Cells Modified with an Improved SB Transposon System. Rotiroti, MC., Buracchi, C., Arcangeli, S., et al.[2021]

Chimeric antigen receptor (CAR)-modified immune effector cell therapies show promise for treating acute myeloid leukemia (AML), similar to their success in B-cell malignancies, but translating this success is challenging due to the need for suitable target antigens and managing potential toxicities.

The review highlights the importance of identifying leukemia-restricted target antigens and strategies to enhance the effectiveness of CAR therapies while minimizing side effects in the immunosuppressive environment of AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML). Acharya, UH., Walter, RB.[2023]

CAR T-cell therapy for acute myeloid leukemia (AML) faces challenges due to the lack of specific surface antigens, but advancements are being made to improve its effectiveness.

Potential strategies to enhance the safety and efficacy of CAR T-cell therapy for AML include reducing the potency of CAR T cells, using transient CAR T cells during pre-transplant conditioning, and employing gene-edited allogeneic stem cell transplants to support sustained anti-AML activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How close are we to CAR T-cell therapy for AML? Gill, SI.[2021]

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]

CAR-T cell therapy has shown promise in treating aggressive hematologic malignancies like acute myeloid leukemia (AML), but its clinical application faces challenges due to the antigenic diversity of AML, which complicates target selection.

Key obstacles for effective CAR-T therapy in AML include the risk of on-target off-tumor toxicities and the unique characteristics of the AML tumor microenvironment, which need to be addressed in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy for Acute Myeloid Leukemia: Preclinical Rationale, Current Clinical Progress, and Barriers to Success. Fiorenza, S., Turtle, CJ.[2021]

The study identifies LILRB4 as a promising tumor-associated antigen specifically expressed on monocytic acute myeloid leukemia (AML) cells, allowing for targeted therapy without affecting normal blood stem cells.

The novel anti-LILRB4 CAR-T cells demonstrated effective targeting and destruction of LILRB4+ AML cells in laboratory tests, while showing no toxicity to normal hematopoietic progenitors, suggesting a safer treatment option for patients with monocytic AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML. John, S., Chen, H., Deng, M., et al.[2020]

CAR T-cell therapy has shown great success in treating B-cell malignancies but faces challenges in effectively targeting myeloid malignancies like acute myeloid leukemia (AML).

Current research is focused on identifying specific target antigens for myeloid leukemia stem cells to improve CAR T-cell therapy's efficacy while reducing harm to healthy blood cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-cell Therapy for Acute Myeloid Leukemia. Bi, X., Hsu, J., Gergis, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06197672

NCT06197672 | Chimeric Antigen Receptor T Cell ... The study will utilize autologous CD4CAR T-cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of ...

2. 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.

3. 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 ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/448655

Chimeric Antigen Receptor T Cell Redirected to Target CD4 ... This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in ...

5. 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.

6. 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 ... The success of chimeric antigen receptor T (CAR-T) cell therapy in acute lymphoblastic leukemia (ALL) has not yet been replicated in AML. There ...