IFN-γ to Treat Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) That Has Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation

NCT ID: NCT04628338

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-08
• Study Completion Date: 2023-10-30

Brief Summary

This study proposes a safe dosing regimen IFN-γ that is sufficient to stimulate IFN-γ receptors on malignant blasts in patients who developed relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after alloSCT with no active or history of III-IV acute graft-versus-host disease (GVHD). It is hypothesized that IFN-γ will promote graft-vs-leukemia (GVL) in patients with AML/MDS that has relapsed after alloSCT.

Detailed Description

Allogeneic hematopoietic stem cell transplantation (alloSCT) can cure patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, relapsed AML/MDS is the most significant single cause of treatment failure, and the majority of relapsed patients ultimately succumb. Alloreactive T cells in the donor graft can kill residual leukemia cells, mediating the graft-vs-leukemia (GVL) effect. Consistent with this, recipients of T cell-depleted grafts have higher rates of relapse. GVL is more potent against chronic leukemias than acute myeloblastic diseases, and the higher incidence of relapse in patients with AML/MDS reflects a failure in GVL.

The central goal of this pilot trial will be to explore whether IFN-γ in this setting is safe and whether it has the desired biological activities on malignant blasts in vivo. IFN-γ will be tested in relapsed patients as monotherapy and in conjunction with donor leukocyte infusions (DLI). The clinical and biological information from this study is essential to design a phase II trial with a therapeutic endpoint.

Treatment will be initiated at 100mcg (almost equal to the dose of 50 mcg/m2 for an adult) three times a week, with the potential to deescalate the frequency of injection for unacceptable toxicity. To explore whether this dosing regimen is sufficient to activate myeloblasts, pre- and post-treatment bone marrow specimens will be harvested to analyze for IFN-γ action (upregulation of HLA class I; HLA class II, ICAM-1 and phosphorylation of STAT1). The primary safety concern is the development of GVHD, which is routinely monitored for all alloSCT patients.

Conditions

Myelodysplastic Syndromes; Myeloid Leukemia; Allogeneic Stem Cell Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IFN-γ

100mcg IFN-γ subcutaneously three times per week (Weeks 0-7), once per week (Weeks 8-12) (or per protocol guidance based on tolerability, response, or DLI infusions)

Group Type: EXPERIMENTAL

IFN-γ (interferon gamma-1b) injection

Intervention Type: DRUG

Dosage form: 100 mcg (2 million International Units) per 0.5 mL solution, administered subcutaneously Dose regimen: three times weekly (Weeks 0-7), once weekly (Weeks 8-12)

Interventions

IFN-γ (interferon gamma-1b) injection

Dosage form: 100 mcg (2 million International Units) per 0.5 mL solution, administered subcutaneously Dose regimen: three times weekly (Weeks 0-7), once weekly (Weeks 8-12)

Intervention Type: DRUG

Other Intervention Names

ACTIMMUNE®

Eligibility Criteria

Inclusion Criteria

• Recipients of allogeneic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome from a human leukocyte antigen (HLA) matched donor
• Relapsed of primary disease with 5% to 20% of blasts in the bone marrow by flow cytometry in the bone marrow with an clear leukemia-associated immunophenotype (If the patient received therapy to treat the relapse, he or she must have 5-20% residual blasts prior to enrollment on this study)
• Performance status KPS score >60% (ECOG 0-2)
• No increases in systemic immunosuppression in the prior four weeks other than to maintain therapeutic levels
• No systemic corticosteroid with a dose higher than 0.5mg/kg/day prednisone or equivalent
• No history of grade IV acute GVHD
• No new systemic immunosuppressive medications in the prior two weeks initiated due to GVHD
• Willingness to have bone marrow and peripheral blood collected as per the study protocol
• Must be able to give informed consent
• Age 18 or older

Exclusion Criteria

• Contraindication to receive IFN-γ including known hypersensitivity to interferon-gamma, E. coli derived products or any component of the product
• Subjects with a positive pregnancy test or who are breastfeeding
• For men or women of childing bearing potential (age < 50 without hysterectomy or oophorectomy or documented menopause), unwilling to use effective contraception for the duration of the study.
• Primary engraftment failure
• Active cardiac arrhythmias not controlled by medical management or current NYHA class II or higher congestive heart failure
• Active ischemic heart disease not well controlled with medications
• A seizure disorder not well controlled by medications
• Estimated GFR <30 mL/min
• AST/SGOT or ALT/SPOT > 5 x ULN
• Total bilirubin > 3 x ULN
• Chemotherapy (other than hypomethylating and/or venetoclax therapy) within the prior 4 weeks
• Body surface area at or less than 1.5 m2, or greater than 2.5 m2 so as to minimize the variation in IFN-γ exposure based on differences in BSA.
• Patients less than 18 years old.
• Pregnant or breastfeeding patients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Horizon Pharma USA, Inc.

INDUSTRY

Sponsor Role: collaborator

Sawa Ito, MD

OTHER

Sponsor Role: lead

Responsible Party

Sawa Ito, MD

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sawa Ito, MD; PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Ito S, Geramita E, Ventura K, Neupane B, Bhise S, Moore EM, Furlan S, Shlomchik WD. IFN-gamma and donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation. JCI Insight. 2025 Mar 25;10(9):e190655. doi: 10.1172/jci.insight.190655. eCollection 2025 May 8.

Reference Type: BACKGROUND

PMID: 40131369 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/40131369/

IFN-γand donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation - PubMed

Other Identifiers

HCC 20-092

Identifier Type: -

Identifier Source: org_study_id