CD33 FPBMC for Acute Myelogenous Leukemia

(AML-MDS 001 Trial)

Overseen By Avani Hopkins

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Virginia

Must be taking: Hypomethylating agents, Venetoclax

Must not be taking: Anti-CD33 therapy, Antileukemic agents

Disqualifiers: Pregnancy, Organ dysfunction, HIV, others

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

Compensation: Varies

Number of Visits: 5

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and potential effectiveness of a new treatment for individuals with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who still have detectable disease after previous treatments. The treatment combines a special type of immune cell therapy (CD33 FPBMC) with a standard treatment, with or without the drug venetoclax. Individuals with AML or MDS who have received prior treatment and still show signs of the disease might be suitable for this study. Participants will receive a series of infusions and follow-up treatments to evaluate the new approach's effectiveness. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot have taken any antileukemic agents or chemotherapy (other than hypomethylating agents or venetoclax) in the last 7 days before joining the study.

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

Research has shown that treatments targeting CD33 are under study for conditions like acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In one study involving a similar treatment, JNJ-67571244, 56 patients with AML participated. The treatment was generally well-tolerated, with some mild to moderate side effects reported.

As this trial is in an early stage, the safety of the treatment is still under evaluation. Early stages focus on assessing safety, so limited safety information may be available at this time. Participants receive weekly doses of CD33 FPBMC, which are blood cells modified to attack cancer cells, along with standard medicines. This combination aims to enhance treatment effectiveness while closely monitoring for any side effects.

For those considering participation, safety remains a top priority, and researchers will carefully monitor participant responses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD33 FPBMC for treating Acute Myelogenous Leukemia (AML) because it uses a novel approach by employing fresh peripheral blood mononuclear cells (FPBMC) to target the CD33 protein on leukemia cells. This is different from traditional AML treatments like chemotherapy or targeted therapy with drugs like venetoclax alone. The combination of CD33 FPBMC with hypomethylating agents, and possibly venetoclax, could offer a more precise attack on leukemia cells, potentially leading to more effective results with fewer side effects. This innovative method has the potential to enhance the immune system's ability to fight leukemia, offering new hope for patients.

What evidence suggests that CD33 FPBMC might be an effective treatment for acute myeloid leukemia?

Research has shown that targeting CD33, a protein found in most acute myeloid leukemia (AML) cells, can be effective. Studies on treatments focusing on CD33 are promising in reducing the disease. In this trial, participants will receive CD33 FPBMC, which combines this targeting with immune cells to potentially attack the cancer more effectively. Early results suggest this method might help patients who still have some disease after standard treatment. The trial will also explore combining CD33 FPBMC with other drugs, such as hypomethylating agents and possibly venetoclax, to boost its effectiveness. Although more research is needed, this approach shows strong potential for fighting AML. ^{1 2 3 6 7}

Who Is on the Research Team?

Daniel Reed, MD

Principal Investigator

Assistant Professor

Lawrence Lum, MD, DSc

Principal Investigator

IND Sponsor

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who still have detectable disease after treatment. Participants should not have received certain prior treatments and must meet specific health conditions to be eligible.

Inclusion Criteria

I have AML and have completed at least 2 cycles of azacitidine and venetoclax.

I have decided on treatment for my cancer's specific genetic changes.

I have relapsed or refractory MDS or MDS/MPN overlap.

Exclusion Criteria

Platelet level of <30,000 platelets/microliter for platelet refractory patients

Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection

I am being considered for a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

White blood cells are collected via leukapheresis procedure and T cells are coated with bispecific antibody

1 week

1 visit (in-person)

Treatment Cycle

Participants receive 4 weekly doses of CD33 FPBMC followed by 4-6 weeks of standard treatment with a hypomethylating agent and possibly venetoclax

8-10 weeks per cycle

4 visits (in-person) for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• CD33 FPBMC

Trial Overview The study tests CD33 FPBMC, a type of immunotherapy given through IV once a week for four weeks, followed by standard care with hypomethylating agents and possibly venetoclax. This can be repeated up to four times as one cycle of the study treatment.

How Is the Trial Designed?

Group I: CD33 FPBMC + hypomethylating agent with or without venetoclax Experimental Treatment 1 Intervention

4 weekly infusions of CD33 fresh peripheral blood mononuclear cells (FPBMC) followed by 4-6 weeks of hypomethylating agent with/without venetoclax.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07270978

Phase Ib Study of CD33 FPBMC in Patients With MRD+ ... The purpose of this study is to understand the safety and estimate the efficacy of combining anti-CD3 x anti-CD33 bispecific antibody ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3383202/

Acute myeloid leukemia stem cells and CD33-targeted ... We review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8722076/

Targeting CD33 for acute myeloid leukemia therapy - PMC The aim of this study was to analyze the level of CD33 expression in patients with newly diagnosed AML and determine its correlation with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694373/

Safety and efficacy of CD33-targeted CAR-NK cell therapy ... In terms of efficacy, newly introduced agents for AML treatment have shown limited effectiveness against R/R AML, with a CR rate of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4644600/

CD33-specific chimeric antigen receptor T cells exhibit ... There have been only modest changes in the treatment of AML over the past 40 years and the prognosis remains poor with average 5-year survival rates of 20%.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10945216/

First‐in‐human study of JNJ‐67571244, a CD33 × CD3 ... Overall, 56 (82.4%) patients had AML, and 12 (17.6%) had high‐risk or very‐high‐risk MDS (Table 1). Median (range) patient age was 66.0 (21–83) ...

7. haematologica.org haematologica.org/article/view/6104

High CD33 expression levels in acute myeloid leukemia ... The aim of this study was to investigate the relationship between the qualitative and quantitative CD33 expression and the presence of mutations of the NPM1 ...