IFN-γ + Donor Leukocyte Infusion for Acute Myeloid Leukemia

Recruiting at 2 trial locations

Overseen By Linda Elias, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sawa Ito, MD

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, Heart disease, Seizures, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with acute myeloid leukemia (AML) who have relapsed after a stem cell transplant. The treatment uses a protein called interferon-gamma (IFN-γ) to target leukemia cells, along with donor leukocyte infusion (DLI), which involves immune cells from a donor. The goal is to determine if this approach can effectively control leukemia. Individuals who have had a stem cell transplant and still show signs of leukemia might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. If you have been on hypomethylating agents, venetoclax, targeted therapies, or cytotoxic chemotherapy, you need to stop at least 2 weeks before starting the trial. For investigational agents, you need to stop at least 4 weeks or 5 half-lives before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Interferon-γ (IFN-γ) has been safe in past studies with patients who have acute myeloid leukemia (AML). A small initial study found that IFN-γ was generally well-tolerated, meaning most people did not experience serious side effects. The most common side effects of IFN-γ include flu-like symptoms, such as fever and tiredness.

For Donor Leukocyte Infusion (DLI), the main concern is a condition called graft-versus-host disease (GVHD), which occurs when donor cells attack the body's own cells. However, DLI has successfully strengthened the immune system's ability to fight leukemia. While there is a risk of GVHD, the benefits of DLI in boosting the body's defenses are considered important in treatment.

Overall, previous research has deemed both IFN-γ and DLI as safe, though some side effects can occur. Clinical trial participants are closely monitored to manage any side effects that might arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Interferon-γ (IFN-γ) and Donor Leukocyte Infusion (DLI) for treating Acute Myeloid Leukemia (AML) because it offers a novel approach compared to standard treatments like chemotherapy and stem cell transplantation. Unlike these traditional methods, which often involve high toxicity and a broad attack on cancer cells, IFN-γ enhances the immune system's ability to target leukemia cells specifically. Additionally, DLI provides a boost of healthy immune cells from a donor, potentially reducing the likelihood of relapse. This dual approach aims to improve the effectiveness of treatment while minimizing the harsh side effects commonly associated with conventional therapies.

What evidence suggests that IFN-γ + Donor Leukocyte Infusion could be effective for acute myeloid leukemia?

This trial will evaluate the combination of Interferon-γ (IFN-γ) with Donor Leukocyte Infusion (DLI) for treating acute myeloid leukemia (AML). Research has shown that this combination may help manage AML, as patients in early studies responded well. IFN-γ proved to be safe and easy for the body to handle. This treatment boosts the immune system to attack leukemia cells, potentially improving outcomes for those with relapsed AML. The goal is to use the body's immune response to target and reduce leukemia cells. ^{6 7 8 9 10}

Who Is on the Research Team?

Sawa Ito, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals who have relapsed Acute Myeloid Leukemia or Myelodysplastic Syndromes after a stem cell transplant. Participants must have had leukemia cells that previously responded to IFN-γ in tests.

Inclusion Criteria

Provision of signed and dated informed consent form

I received a stem cell transplant for AML or MDS from a donor who was an HLA match.

I am able to care for myself and perform daily activities.

Exclusion Criteria

Positive pregnancy test or currently breastfeeding on Day 1 of study treatment

My bone marrow transplant didn't work as expected.

I have not taken any immunosuppressive medications in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IFN-γ monotherapy for 4 weeks, followed by combination with Donor Leukocyte Infusion (DLI) for additional 8 weeks

12 weeks

Weekly visits for clinical assessment and treatment administration

Follow-up

Participants are monitored for safety, effectiveness, and adverse events after treatment

Up to 12 months

Monthly visits (in-person) for the first 6 months, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Donor Leukocyte Infusion (DLI)
• Interferon-γ (IFN-γ)

Trial Overview

The study is testing the effectiveness of Interferon gamma-1b combined with Donor Leukocyte Infusion (DLI) on patients. It's a phase 2 trial building on earlier positive results, and includes detailed analysis of how leukemia cells react to treatment.

How Is the Trial Designed?

Group I: IFN-γ + DLI Experimental Treatment 2 Interventions

ACTIMMUNE® (IFN-γ-1b) at a dose of 50 mcg/m\^2 (All participants will receive a 4-week period of IFN-γ monotherapy with ACTIMMUNE 100 mcg 3 times a week. This dose and schedule will be continued for 4 additional weeks and then tapered to 100 mcg weekly for an additional 4 weeks) DLI at a dose of 10\^7 CD3+ cells/kg (DLI doses will be given pending clinical assessment for disease, graft versus host disease (GVHD) and peripheral blood donor chimerism the week prior to DLI. Second DLI dose is only offered to subjects with residual disease not requiring cytotoxic therapy and without GVHD)

Interferon-γ (IFN-γ) is already approved in United States, European Union for the following indications:

Approved in United States as ACTIMMUNE for:

• Chronic Granulomatous Disease
• Severe Malignant Osteopetrosis

Approved in European Union as Interferon gamma-1b for:

• Chronic Granulomatous Disease

Who Is Running the Clinical Trial?

Sawa Ito, MD

Lead Sponsor

Trials

2

Recruited

50+

Evans MDS Discovery Research Grant

Collaborator

Trials

1

Recruited

50+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

FDA Office of Orphan Products Development

Collaborator

Trials

73

Recruited

6,400+

Published Research Related to This Trial

In a phase 1 trial involving 9 pediatric and young adult patients with relapsed acute myeloid leukemia (AML) after hematopoietic cell transplantation, donor-derived memory-like natural killer (ML NK) cells showed significant antileukemic activity, leading to complete remission in 4 out of 8 evaluable patients by day 28.

The ML NK cells expanded and persisted for over 3 months without significant toxicity, suggesting that this approach, combined with donor lymphocyte infusions, could be a promising new immunotherapy for relapsed AML in a post-transplant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant. Bednarski, JJ., Zimmerman, C., Berrien-Elliott, MM., et al.[2023]

In a study of 57 refractory acute myeloid leukemia (AML) patients, the use of interleukin (IL)-2-diphtheria fusion protein (IL2DT) significantly improved the expansion of donor natural killer (NK) cells and led to higher complete remission rates (53% vs 21%) and better disease-free survival at 6 months (33% vs 5%).

The study found that effective depletion of regulatory T-cells (Tregs) was crucial for NK cell expansion and clinical outcomes, highlighting the importance of optimizing the cytokine environment to enhance the efficacy of NK cell therapies in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Bachanova, V., Cooley, S., Defor, TE., et al.[2022]

Recombinant human TNF-alpha and IFN-gamma can induce functional and morphological maturation in myeloid leukemic cells from patients with acute myeloid leukemia, suggesting a potential therapeutic role in promoting differentiation of these cancer cells.

In a study involving 16 patients, both cytokines significantly inhibited the growth of leukemic cells and enhanced cell adherence, with their combination leading to greater growth inhibition, indicating a synergistic effect in treating leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia. Geissler, K., Tricot, G., Leemhuis, T., et al.[2011]

Researchers developed a stable STAT3 decoy oligodeoxynucleotide (dODN) that specifically targets cells and enhances the immune response against acute myeloid leukemia (AML).

The dODN works by restoring the body's natural ability to fight AML, highlighting its potential as a novel therapeutic approach in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A STAT3 decoy lures AML out of hiding. Redell, MS.[2021]

In a study involving 13 acute myeloid leukemia (AML) samples, 69% of initially CD14(-) samples were able to express CD14 after in vitro expansion, indicating a successful method to prepare cells for further treatment.

The expanded CD14(+) leukemic cells showed a high likelihood of differentiating into dendritic cells when treated with specific cytokines, which could increase the number of patients eligible for dendritic cell-based immunotherapy to prevent AML relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Procedures for the expansion of CD14(+) precursors from acute myeloid leukemic cells to facilitate dendritic cell-based immunotherapy. van den Ancker, W., Wijnands, PG., Ruben, JM., et al.[2017]

Adoptive NK cell infusion using clinical-grade membrane-bound IL-21/4-1BBL-expanded NK cells showed significant antileukemic activity against acute myeloid leukemia (AML) in both laboratory and animal studies, with expanded NK cells persisting in the body for at least 13 days after infusion.

Patients with minimal residual disease (MRD+) who received NK cell treatment experienced better overall survival compared to those undergoing standard consolidation therapy, with no major adverse events reported, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded clinical-grade membrane-bound IL-21/4-1BBL NK cell products exhibit activity against acute myeloid leukemia in vivo. Zhao, XY., Jiang, Q., Jiang, H., et al.[2021]

Interferon-gamma (IFN-gamma) can enhance the growth of clonogenic blasts in most acute myeloblastic leukemia (AML) patients when combined with hematopoietic growth factors like interleukin-3, showing a synergistic effect in 13 out of 15 cases studied.

The growth effects of IFN-gamma are mediated by tumor necrosis factor alpha (TNF alpha), as blocking TNF alpha reduced the growth enhancement, indicating that IFN-gamma's role can vary between promoting and inhibiting cell proliferation depending on the cell type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-gamma enhances growth factor-dependent proliferation of clonogenic cells in acute myeloblastic leukemia. Murohashi, I., Hoang, T.[2021]

Recombinant IFN-gamma showed the ability to induce differentiation of leukemic cells and inhibit their growth in vitro, while IFN-alpha was ineffective, suggesting a specific therapeutic role for IFN-gamma in acute myelogenous leukemia (AML).

In a patient with AML, intravenous treatment with IFN-gamma led to complete hematologic remission and significant changes in bone marrow characteristics, indicating its potential as an effective treatment option for selected AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon. Beran, M., Andersson, B., Kantarjian, H., et al.[2013]

Allogeneic monocyte-derived dendritic cells (mDCs) pulsed with leukemic lysates showed superior ability to stimulate T cells and produce immune response markers compared to both leukemic and autologous mDCs.

These allogeneic mDCs can effectively generate leukemia-specific cytotoxic T cells, suggesting they may be a promising alternative for immunotherapy in acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monocyte-derived dendritic cells from HLA-matched allogeneic donors showed a greater ability to induce leukemic cell-specific T cells in comparison to leukemic cell-derived dendritic cells or monocyte-derived dendritic cells from AML patients. Lee, JJ., Choi, BH., Kang, HK., et al.[2023]

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