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

Trial Summary

What is the purpose of this trial?

This is a phase 1 study (the first stage in testing a new treatment to see how safe and tolerable the treatment is) which will include patients with acute myeloid leukemia (AML) that has either returned or has a more than a 70% chance of coming back and cannot have a bone marrow transplant. 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 with AML that cannot have bone marrow transplants.

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.

What data supports the effectiveness of the treatment IL-12 for Acute Myeloid Leukemia?

Research shows that IL-12 can significantly delay tumor growth in a mouse model of acute myeloid leukemia (AML) and, when used in a vaccine form, can cure mice with a high leukemia burden. Additionally, IL-12 has been shown to reduce new blood vessel formation and inhibit tumor cell growth in human AML cell lines, suggesting its potential as a treatment for AML. ^{1 2 3 4 5}

What safety data exists for IL-12 treatment in humans?

IL-12 has been tested in clinical trials for cancer, showing some side effects like fever, flu-like symptoms, fatigue, joint and muscle pain, low white blood cell count, and liver issues. However, in some studies, IL-12 was used safely in mice without signs of toxicity, and strategies are being developed to reduce its toxic effects in humans. ^{1 2 3 6 7}

How does the IL-12 treatment for acute myeloid leukemia differ from other treatments?

IL-12 is unique because it is an immunotherapy that stimulates the body's immune system to fight leukemia by enhancing the activity of T cells and natural killer cells, unlike traditional chemotherapy that directly targets cancer cells. It has shown potential in preclinical studies to induce long-lasting immune responses and reduce tumor growth without significant toxicity. ^{1 2 3 7 8}

Research Team

Hassan Sibai, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Absence of IL-12Rβ2 in CD33(+)CD38(+) pediatric acute myeloid leukemia cells favours progression in NOD/SCID/IL2RγC-deficient mice. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Direct inhibition of human acute myeloid leukemia cell growth by IL-12. [2021]

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

Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg-/- mice. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Targeting acute myeloid leukemia cells with cytokines. [2012]

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

Preclinical validation: LV/IL-12 transduction of patient leukemia cells for immunotherapy of AML. [2020]

7. Japan pubmed.ncbi.nlm.nih.gov

[Clinical trial of IL-12 for cancer patients]. [2007]

8. China pubmed.ncbi.nlm.nih.gov

[Diagnostic Values of IL-12 and IFN-γ for the Patients with Acute Leukemia]. [2018]