CAR T-Cell Therapy for Acute Myeloid Leukemia

Overseen by Karamjeet Sandhu, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Active infection, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment where immune cells are modified to better attack leukemia cells. It targets patients whose leukemia has returned or is resistant to other treatments. The modified immune cells are designed to specifically recognize and kill cancer cells.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as systemic steroids and immunosuppressants, 28 days before joining. If you're on antifungal treatment, you must stop it 8 weeks before enrolling, but antifungal prevention is allowed.

What data supports the effectiveness of the treatment CAR T-Cell Therapy for Acute Myeloid Leukemia?

Research shows that CAR T-Cell Therapy targeting CD33 can effectively kill leukemia cells in lab tests and animal studies. This treatment has shown promise in reducing leukemia and delaying disease progression, making it a potential option for patients with acute myeloid leukemia. ^{1 2 3 4 5}

Is CAR T-cell therapy for acute myeloid leukemia safe?

Research on CD33-directed CAR T-cell therapy for acute myeloid leukemia (AML) shows that while it has potential, safety data is limited. A study on a similar therapy, CD33-CAR NK cells, found no significant adverse effects at certain doses, suggesting a favorable safety profile, but more research is needed to confirm this for CAR T-cells. ^{1 3 5 6 7}

How is Anti-CD33 CAR T-cell therapy different from other treatments for acute myeloid leukemia?

Anti-CD33 CAR T-cell therapy is unique because it uses genetically engineered T cells to specifically target and kill leukemia cells that express the CD33 protein, which is present in about 90% of acute myeloid leukemia cases. This approach is different from traditional treatments as it offers a targeted immunotherapy option, potentially improving outcomes for patients who do not respond well to conventional therapies. ^{1 3 5 6 8}

Research Team

Karamjeet Sandhu, M.D.

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults with acute myeloid leukemia (AML) that has returned or is unresponsive to treatment, who have a life expectancy of at least 16 weeks and are in relatively good health as indicated by certain organ function tests. Participants must not be pregnant, agree to use birth control, and have a potential stem cell donor. Those with active autoimmune diseases, other cancers, significant heart issues within the past 6 months, or infections like HIV or hepatitis are excluded.

Inclusion Criteria

My cancer has been confirmed to be CD33 positive within the last 3 months.

Participants with Gilbert syndrome may be included if their total bilirubin is =< 3.0

Assent, when appropriate, will be obtained per institutional guidelines

Exclusion Criteria

Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures

My heart rhythm problem is not stable, even with medication, and I'm about to undergo leukapheresis.

I am not pregnant or breastfeeding.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion

1 week

1 visit (in-person)

Treatment

Patients receive anti-CD33 CAR T-cells intravenously on day 0

1 day

1 visit (in-person)

Optional Re-treatment

Patients with persistent CD33+ AML may optionally receive additional anti-CD33 CAR T-cells if eligible

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Treatment Details

Interventions

• Anti-CD33 CAR T-cells (CAR T-cell Therapy)
• Lymphodepletion Therapy (Procedure)

Trial Overview The trial is testing anti-CD33 CAR T-cell therapy for AML patients whose cancer has either come back after treatment or hasn't responded at all. The therapy involves modifying immune cells to target cancer cells more effectively. It's in phase I to determine safety and optimal dosing.

Participant Groups

Group I: Treatment (anti-CD33 CAR T-cells) Experimental Treatment 2 Interventions

Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells IV on day 0. Patients with persistent CD33+ AML who are \> 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

A novel second-generation chimeric antigen receptor (CAR) targeting CD33 has been developed, showing effectiveness in redirecting T cells to kill acute myeloid leukemia (AML) cells, which express CD33 in about 90% of cases.

In pre-clinical studies, this CAR therapy demonstrated significant anti-leukemia effects both in vitro and in vivo, effectively preventing leukemia development and delaying disease progression in mice, supporting its potential as a clinical treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. O'Hear, C., Heiber, JF., Schubert, I., et al.[2021]

The development of bispecific CAR T cells targeting both CD33 and CD123 shows promise in controlling acute myeloid leukemia (AML) without causing on-target off-tumor toxicities, which is a common issue with therapies targeting these markers.

In preclinical tests using a mouse model, the bispecific CAR T cells demonstrated similar effectiveness in controlling AML as traditional monospecific CAR T cells, suggesting they could be a safer and effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CD33/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. Boucher, JC., Shrestha, B., Vishwasrao, P., et al.[2023]

CAR T-cell therapy has the potential to improve outcomes for patients with acute myeloid leukemia (AML) by specifically targeting leukemia cells, but there are significant challenges to its effectiveness and safety.

Strategies being explored to enhance CAR T-cell therapy in AML include targeting specific leukemia antigens to reduce side effects, using checkpoint inhibitors to counteract immune suppression caused by leukemia, and developing allogenic CAR T cells to make the treatment more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. Badar, T., Manna, A., Gadd, ME., et al.[2022]

Cytokine-induced killer (CIK) cells modified to express anti-CD123 CAR are effective in reducing leukemia burden in acute myeloid leukemia (AML) while sparing normal hematopoietic stem/progenitor cells, making them a safer treatment option.

In contrast, anti-CD33 CAR T cells also reduce leukemia but risk damaging normal blood cell production due to CD33 expression on healthy cells, highlighting the potential advantages of targeting CD123 in immunotherapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Pizzitola, I., Anjos-Afonso, F., Rouault-Pierre, K., 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]

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 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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Bispecific CD33/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. [2023]

5. United States 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Current challenges for CAR T-cell therapy of acute myeloid leukemia. [2020]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. [2023]