IL-12 for Acute Myeloid Leukemia

Overseen By Hassan Sibai, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must not be taking: Chemotherapy, Corticosteroids, Cox2 inhibitors

Disqualifiers: ECOG >2, CNS disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with acute myeloid leukemia (AML), a type of blood cancer that cannot be treated with a bone marrow transplant. The researchers aim to determine the safety and efficacy of modifying a patient’s AML cells to produce IL-12, a protein that could help fight cancer, and then reintroducing these cells to the patient. Eligible participants have AML that is likely to recur, cannot undergo a transplant, but are stable and not currently receiving chemotherapy. 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.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking chemotherapy, corticosteroids, Cox2 inhibitors, or any non-drug therapies aimed at altering the immune response or killing leukemic cells within one week before receiving IL-12, except for azacytidine.

Is there any evidence suggesting that IL-12 is likely to be safe for humans?

Research suggests that IL-12 might be safe for patients with acute myeloid leukemia (AML). Studies have shown that using IL-12 in a treatment called IL12-AML vaccination is safe and may help the immune system eliminate remaining cancer cells after treatment. This suggests that IL-12 could be well-tolerated in humans.

IL-12 enhances the body's immune system to target cancer cells more effectively. In early tests conducted before human trials, modified leukemia cells produced IL-12 protein, which successfully activated the immune response.

Since this study is in an early phase, it primarily focuses on testing safety and tolerability. As a result, limited human data is available at this time. However, these initial findings provide some confidence in the treatment’s safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

IL-12 is unique because it introduces a new mechanism of action in treating acute myeloid leukemia (AML). Unlike traditional chemotherapy or targeted therapies, which focus on directly killing cancer cells or inhibiting specific proteins, IL-12 works by stimulating the immune system to attack the cancer. This novel approach involves using IL-12 to boost the body's natural defenses, potentially leading to a more targeted and less toxic treatment. Researchers are excited about IL-12 because it represents a shift towards harnessing the immune system, offering hope for more effective and personalized treatments for AML.

What evidence suggests that IL-12 might be an effective treatment for acute myeloid leukemia?

Research has shown that IL-12, a protein crucial to the immune system, can inhibit the growth of acute myeloid leukemia (AML) cells. In earlier studies, researchers modified AML cells to produce IL-12, and these cells successfully generated active IL-12, indicating promise for treatment. In this trial, participants will receive a single dose of IL-12 intravenously to further assess its potential in targeting the growth of cancer cells in AML. This treatment remains under study to confirm its safety and effectiveness for patients. ^{1 4 5 6 7}

Who Is on the Research Team?

Hassan Sibai, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with Acute Myeloid Leukemia (AML) whose disease has returned or is likely to, and who can't have a bone marrow transplant. They must have had prior treatment but not be in remission, with stable white blood cell counts and less than 10% blast cells post-therapy. Participants need functioning kidneys and liver, agree to contraception use, are not pregnant, and can follow study procedures.

Inclusion Criteria

My bone marrow has less than 10% blast cells after initial treatment and I don't want more intense therapy.

Agree to use contraception

Agrees to participate in the study and signs the informed consent

Exclusion Criteria

Greater than 10% blasts in the bone marrow or circulating blast cells

Life expectancy < 2 months

Patients who are HIV positive

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

A single dose of IL-12 is given intravenously to participants

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

Day 28 to 2 years

Weekly visits

What Are the Treatments Tested in This Trial?

Interventions

• IL-12

Trial Overview The trial tests the safety of using modified AML cells that produce IL-12 in patients. It's a phase 1 study focusing on those who cannot undergo bone marrow transplants to see if this approach helps manage their leukemia by enhancing their immune response against cancer cells.

How Is the Trial Designed?

Group I: IL-12 Experimental Treatment 1 Intervention

A single dose of IL-12, given intravenously.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Published Research Related to This Trial

Interleukin-12 (IL-12) has shown promise in animal studies for controlling tumor growth at nontoxic doses, and it is currently being tested in clinical trials for its potential as an anti-cancer treatment.

While some patients have experienced partial responses to IL-12, the treatment is associated with side effects like flu-like symptoms and liver dysfunction, highlighting the need for further research on its mechanisms and safety in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical trial of IL-12 for cancer patients]. Ohe, Y., Kasai, T., Heike, Y., et al.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5142463/

Preclinical validation: LV/IL-12 transduction of patient ... A range of 20–70% functional transduction efficiencies was achieved. Transduced acute myeloid leukemia cells produced bioactive IL-12 protein ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165247810001963

Direct inhibition of human acute myeloid leukemia cell ... This study shows for the first time that IL-12 targets directly AML cell growth and paves the way to further investigation of IL-12 as potential drug for AML ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7006625/

Inflammatory biomarkers and patient-reported outcomes in ... Previous studies have found correlations between inflammatory cytokines and patient-reported outcomes such as fatigue and quality of life (QOL) in patients ...

4. exphem.org exphem.org/article/S0301-472X(05)00393-0/fulltext

Interleukin-12 production by leukemia-derived dendritic ... IL-12 gene can be successfully expressed into AML-DCs defective in endogenous IL-12 production by using a novel nonviral method that does not modify their ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1000996/full

The cytokine network in acute myeloid leukemia In AML patients, multiple studies have reported increased levels of IL-1β and IL-1 receptors as well as decreased levels of interleukin-1 receptor antagonist ( ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497120366611

Vaccines With Interleukin-12–Transduced Acute Myeloid ... Our results demonstrate that IL12-AML vaccination is a safe and potent immunotherapeutic approach that has a great potential to eliminate minimal residual ...

7. ctv.veeva.com ctv.veeva.com/study/a-study-of-interleukin-12-il-12-in-patients-with-acute-myelogenous-leukemia-aml

A Study of (Interleukin-12) IL-12 in Patients With Acute ... This study will see whether modifying a patient's AML cells to produce IL-12 and giving it back to the patient is safe and useful in patients ...