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

NCT04628338 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: HCC 20-092
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes; Myeloid Leukemia; Allogeneic Stem Cell Transplantation

Keywords

allogeneic hematopoietic stem cell transplantation; acute myeloid leukemia; myelodysplastic syndrome; graft versus host disease; AML; MDS; alloSCT; GVHD; interferon-gamma-1b; Actimmune; IFN-g; donor lymphocyte infusion

Outcome Measures

Primary Outcomes (5)

• Upregulation HLA l (HLA-ABC)

  Upregulation of HLA l (HLA-ABC) in bone marrow malignant blasts post-IFN-γ treatment, measured by the change in mean florescent intensity by flow cytometry.

  Up to 6 months

• Upregulation of HLA ll (HLA-DR/DQ)

  Upregulation of HLA ll (HLA-DR/DQ) in bone marrow malignant blasts post-IFN-γ treatment, measured by the change in mean florescent intensity by flow cytometry.

  Up to 6 months

• Upregulation of ICAM-1

  Upregulation of ICAM-1 in bone marrow malignant blasts post-IFN-γ treatment, measured by the change in mean florescent intensity by flow cytometry as a percentage of positive cells.

  Up to 6 months

• Adverse events related to IFN-γ

  Adverse events of IFN-γ in relapsed patients after alloSCT per CTCAE v5.0.

  Up to 6 months

• Generation of phosphorylated-STAT1

  Generation of phosphorylated-STAT1 in bone marrow malignant blasts post-IFN-γ treatment, measured by the change in mean florescent intensity by flow cytometry as a percentage of positive cells.

  Up to 6 months

Secondary Outcomes (3)

• Malignant Blast Burden

  Up to 6 months

• Incidence of GVHD

  Up to 6 months

• Incidence of de novo GVHD

  Up to 6 months

Study Arms (1)

IFN-γ

EXPERIMENTAL

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)

Drug: IFN-γ (interferon gamma-1b) injection

Interventions

IFN-γ (interferon gamma-1b) injection 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)

Also known as: ACTIMMUNE®

IFN-γ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sawa Ito, MD: lead
• Horizon Pharma USA, Inc.: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• 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.

  PMID: 40131369 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Graft vs Host Disease

Interventions

interferon gamma-1b; Injections

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Neoplasms by Histologic Type; Neoplasms; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Sawa Ito, MD; PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 13, 2020
• Study Start: March 8, 2021
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2023
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)