CAR T-cell Therapy for Acute Myeloid Leukemia

Overseen By LaQuisa HIll, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: High dose steroids

Disqualifiers: APL, Active infection, Second cancer, others

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

Compensation: Varies

Number of Visits: 5

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 has returned or hasn't responded to other treatments. The treatment uses specially modified immune cells, known as CAR T-cells, designed to better target and destroy cancer cells. Researchers hope these enhanced cells will more effectively fight leukemia. Suitable candidates for this trial include those with AML that has recurred or persisted after treatment and who are considering a stem cell transplant. 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 protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic chemotherapy at least 2 weeks before the study treatment and must not be on high-dose steroids or certain immune-suppressing drugs. 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 CLL-1 CAR-T cell therapy could be promising for treating Acute Myeloid Leukemia (AML). Studies have found that most people tolerate this treatment well. While some side effects occur, they are usually manageable and not severe. Common side effects might include fever or low blood cell counts, typical with many cancer treatments.

Similar therapies have been used safely in other AML studies. This treatment uses modified T cells, a type of immune cell, to find and destroy cancer cells. Researchers have experience with this approach and know how to manage any side effects that might occur.

As a Phase 1 trial, the main goal is to test the treatment's safety. Researchers closely monitor how the body responds to the therapy. Overall, early studies suggest that CLL-1 CAR-T cells are a safe option for people with relapsed AML. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for acute myeloid leukemia (AML) involve chemotherapy, radiation, or stem cell transplants, which target rapidly dividing cells but can also harm healthy cells. CLL-1.CAR T-cell therapy is unique because it uses genetically engineered T-cells to specifically target and destroy leukemia cells. This approach harnesses the body's own immune system, potentially offering a more precise attack on cancer cells with fewer side effects. Researchers are excited about this treatment because it represents a more targeted and personalized approach, showing promise in overcoming resistance seen with traditional therapies.

What evidence suggests that CLL-1 CAR-T cells might be an effective treatment for acute myeloid leukemia?

Research has shown that CLL-1 CAR-T cell therapy, which participants in this trial will receive, could be a promising treatment for acute myeloid leukemia (AML). Studies have found it effective in managing AML that has returned after treatments like stem cell transplants. Patients who received CLL-1 CAR-T cells experienced benefits, although some encountered more side effects. This therapy uses T cells, modified to better find and destroy leukemia cells. Adding CD28 to these cells helps them grow and last longer, enhancing their effectiveness against cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

LaQuisa Hill, MD

Principal Investigator

Cell and Gene Therapy, Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults up to 75 years old with Acute Myeloid Leukemia (AML) that's resistant or returned after treatment. They must have a certain level of CLL-1 protein on their cancer cells, good kidney and liver function, no active infections, HIV or HTLV, not be taking high-dose steroids for GVHD, and not have another active cancer.

Inclusion Criteria

Serum Creatinine < 1.5 x ULN

PT and APTT <1.5x ULN

AST < 1.5 x ULN

Exclusion Criteria

I do not have an active HIV or HTLV infection.

I am currently on high-dose steroids or other immune-suppressing drugs for GVHD.

I have an ongoing infection that isn't getting better despite treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-treatment Chemotherapy

Participants receive cyclophosphamide and either fludarabine or clofarabine to lower T cell counts before CAR-T cell infusion

1 week

3 visits (in-person)

CAR-T Cell Infusion

Participants receive an infusion of CLL-1 chimeric antigen receptor T-cells

1 day

1 visit (in-person)

Initial Monitoring

Participants are monitored closely for side effects and response to treatment, including potential hospital admission for 72 hours

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular blood tests and imaging

15 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CLL-1.CAR T cells

Trial Overview The study tests CAR-T cells targeting the CLL-1 antigen in AML patients. These modified T-cells are equipped with an antibody against CLL-1 and a CD28 stimulator to enhance their growth and persistence in the body. This investigational therapy aims to improve the immune system's ability to fight leukemia.

How Is the Trial Designed?

Group I: CLL-1.CAR Experimental Treatment 1 Intervention

Group A

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

CLL-1.CAR-T cells specifically target and kill acute myeloid leukemia (AML) cells while sparing normal hematopoietic stem cells, which is crucial for reducing the risk of severe toxicity during treatment.

The introduction of an inducible caspase-9 suicide gene system allows for controlled elimination of CLL-1.CAR-T cells, providing a safety mechanism to manage potential side effects from cytotoxic activity against normal myeloid cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Acute Myeloid Leukemia with T Cells Expressing Chimeric Antigen Receptors Directed to C-type Lectin-like Molecule 1. Tashiro, H., Sauer, T., Shum, T., et al.[2022]

In a trial involving four pediatric patients with refractory/relapsed acute myeloid leukemia (R/R-AML), three patients achieved complete remission and were free of minimal residual disease after receiving anti-CLL1 CAR T-cell therapy, indicating promising efficacy.

The treatment was associated with low-grade and manageable adverse events, suggesting that this CAR T-cell therapy could be a safe alternative for children with R/R-AML, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CLL1 Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed/Refractory Acute Myeloid Leukemia. Zhang, H., Wang, P., Li, Z., 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]

In a phase 1/2 clinical trial involving 8 children with relapsed or refractory acute myeloid leukemia (R/R-AML), anti-CLL1 CAR-T cell therapy demonstrated a favorable safety profile, with only mild cytokine release syndrome observed and no fatal events reported.

The treatment showed promising efficacy, with 4 out of 8 patients achieving a morphologic leukemia-free state and minimal residual disease negativity, indicating that anti-CLL1 CAR-T cell therapy could be a viable option for these young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis. Zhang, H., Bu, C., Peng, Z., et al.[2023]

CAR-T cells targeting CLL-1 were successfully developed and showed a high transduction rate of 77.82%, effectively killing CLL-1-expressing acute myeloid leukemia (AML) cells in both in vitro and in vivo models.

In a human xenograft mouse model, CLL-1 CAR-T cells significantly improved survival compared to untransduced T cells, demonstrating potent antileukemic activity with a median survival of not reached versus 22 days for the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development and functional verification of CAR-T cells targeting CLL-1]. Chai, X., Jin, X., Zhao, MF.[2022]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2106/504065/A-Phase-I-Clinical-Trial-of-CLL-1-CAR-T-Cells-for

A Phase I Clinical Trial of CLL-1 CAR-T Cells for the ... This is a single-center, phase I, dose-escalation trial of CLL-1 CAR-T cell in adult patients with r/r AML (ChiCTR2000041054）admitted to Tianjin ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04884984

Study Details | NCT04884984 | Anti-CLL1 CAR T-cell ... This is a single center, open-label phase 1/2 study to evaluate the safety and efficacy of anti-CLL1 chimeric antigen receptor engineered T cell immunotherapy ( ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39896798/

Utilization of donor CLL-1 CAR-T cells for the treatment ... The CLL-1 CAR-T cells therapy derived from allogeneic donors demonstrates both safety and efficacy in the management of relapsed AML following allogeneic HSCT.

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05705-7

Efficacy and safety of CAR-T therapy targeting CLL1 in ... Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence ...

5. 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 ... Targeting CLL1 in adults demonstrated similar positive results but with increased toxicity. A single trial (ChiCTR2000041054) treating 10 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05016063

Study Details | NCT05016063 | Dual CD33-CLL1-CAR-T ... Phase I, interventional, single-arm, open-label, treatment study to evaluate the safety and effectiveness of CD33-CLL1 CAR in patients with relapsed and/or ...