Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation

NCT ID: NCT06529731

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-23
• Study Completion Date: 2027-10-31

Brief Summary

This phase 2 study aims to confirm the efficacy seen in the prior phase 1 trial, and further contribute to this effort through the collection of leukemia cells pre- and post- in vivo IFN-γ therapy. As in the previously conducted phase 1 trial, this trial will test whether leukemia blasts were responsive to IFN-γ in vitro and in vivo, with single-cell RNA sequencing (scRNAseq) conducted to understand the transcriptomic changes induced by IFN-γ in leukemia cell subsets, including those with stem cell characteristics.

Detailed Description

This novel regimen has the potential to fill a large unmet need for this high-risk population of patients who have few, if any, effective therapeutic options. If this trial confirms the clinical efficacy of IFN-γ/DLI, it will establish a new standard of care for post-transplant AML/MDS relapse. It would also provide a rationale to explore other indications for IFN-γ in the context of an alloSCT, including 1) IFN-γ/DLI for relapsed disease after haploidentical alloSCT; 2) pre-emptive post-alloSCT treatment of patients transplanted with measurable residual disease (MRD) or with poor-risk AML/MDS such as with TP53 mutations; and 3) prevention of relapse in patients who can only tolerate reduced-intensity conditioning regimens which in most studies results in higher rates of post-alloSCT AML/MDS relapse than when intensive conditioning regimens are employed. Together, this work would allow more patients with AML/MDS to be referred for and ultimately benefit from an alloSCT.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Study Design

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

Study Groups

IFN-γ + DLI

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)

Group Type: EXPERIMENTAL

Interferon gamma-1b

Intervention Type: DRUG

ACTIMMUNE/Interferon gamma-1b is a single-chain polypeptide containing 140 amino acids that is produced by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes for the recombinant protein. Interferon gamma-1b is part of a drug regimen used to treat Chronic Granulomatous Disease, or CGD. CGD is a genetic disorder, usually diagnosed in childhood, that affects some cells of the immune system and the body's ability to fight infections effectively.

Donor Leukocyte Infusion (DLI)

Intervention Type: BIOLOGICAL

Donor lymphocyte infusion is a procedure that transfers healthy white blood cells (lymphocytes) from a bone marrow or stem cell donor to a recipient's blood. An infusion of healthy lymphocytes helps the recipient's immune system get rid of remaining cancer cells if they have a relapse after a bone marrow or stem cell transplant for blood cancer.

Interventions

Interferon gamma-1b

ACTIMMUNE/Interferon gamma-1b is a single-chain polypeptide containing 140 amino acids that is produced by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes for the recombinant protein. Interferon gamma-1b is part of a drug regimen used to treat Chronic Granulomatous Disease, or CGD. CGD is a genetic disorder, usually diagnosed in childhood, that affects some cells of the immune system and the body's ability to fight infections effectively.

Intervention Type: DRUG

Donor Leukocyte Infusion (DLI)

Donor lymphocyte infusion is a procedure that transfers healthy white blood cells (lymphocytes) from a bone marrow or stem cell donor to a recipient's blood. An infusion of healthy lymphocytes helps the recipient's immune system get rid of remaining cancer cells if they have a relapse after a bone marrow or stem cell transplant for blood cancer.

Intervention Type: BIOLOGICAL

Other Intervention Names

ACTIMMUNE®

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Recipients of an alloSCT for AML or MDS from a minimally 8/8 HLA-matched donor

3. AML/MDS relapsed post-alloSCT with measurable residual disease defined by either of the following criteria:

1. At least 5% or more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall 36

2. At least 0.1% of abnormal myeloblasts with a leukemia-associated immunophenotype (LAIP) by multiparameter flow cytometry. The abnormal cells with LAIP should not exceed 30% of nucleated cells.

3. Recurrent or persistent cytogenetic abnormalities detectable by FISH or karyotype analysis.

4. For patients with mutant NPM1, at least 1,000 mutant transcript copies per 106 ABL or equivalent housekeeping transcripts in bone marrow by qPCR or dPCR

4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2

5. A DLI is available, or the donor is available and agrees to undergo apheresis to collect lymphocytes for infusion

6. If salvage therapy for post-alloSCT relapse was received, the therapy is limited to 1 line of the following:

1. For hypomethylating agents, venetoclax, and targeted therapies (e.g., tyrosine kinase inhibitors, IDH1/IDH2 inhibitors, or FLT3 inhibitors), the last dose must be > 2 week prior to the initiation of IFN-γ

2. For cytotoxic chemotherapy agents, the last dose must be >2 weeks prior to start of treatment for the present study

3. For investigational agents, the last dose must be ≥ 4 weeks or 5 half-lives (whichever is longer) prior to the start of treatment for the present study

7. Provision of signed and dated informed consent form

8. Stated willingness to comply with all study procedures and availability for the duration of the study

9. For female subject, who is < 55 years old without hysterectomy, oophorectomy or documented menopause, willingness to use two forms of contraception including one form of highly effective contraception (i.e., long-acting reversible contraception, oral contraceptive pills) for the duration of the study

10. For male subject, willingness to use highly effective contraception methods including male condoms by male subject and one form of highly effective contraception by his female partner (i.e., long-acting reversible contraception, oral contraceptive pills) for the duration of the study

Exclusion Criteria

1. Primary engraftment failure after alloSCT

2. Grade 3 or 4 aGVHD per Mount Sinai Acute GVHD International Consortium (MAGIC) at the time of planned enrollment

3. History of grade 4 aGVHD per the MAGIC criteria

4. Moderate or severe cGVHD per NIH Consensus Criteria at time of planned enrollment

5. Any systemic immunosuppressive medications taken within 2 weeks before the enrollment

6. Grade 3 or higher non-hematologic toxicity related to any prior therapy at the time of enrollment

7. A contraindication to receive IFN-γ including a known hypersensitivity to IFN-γ, E. coli derived products or any other component of the product

8. Positive pregnancy test or currently breastfeeding on Day 1 of study treatment 37

9. Active cardiac arrhythmia not controlled by medical management or current NYHA class II or higher congestive heart failure within 2 months of enrollment unless it was due to a tachyarrhythmia which is under control at the time of enrollment

10. Active ischemic heart disease not controlled with medications within 2 months of enrollment

11. Acute or chronic pulmonary disease requiring continuous oxygen treatment

12. Seizure disorder not controlled by medications within 2 months of enrollment

13. AST or ALT > 5x ULN or total bilirubin >3x ULN at time of enrollment

14. Renal function CrCl <30 mL/min at time of enrollment using modified Cockcroft-Gault formula

15. Body surface area ≤ 1.5 m2 or ≥ 2.5 m2 so as to minimize variation in IFN-γ exposure based on differences in body surface area

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

Sponsors

Evans MDS Discovery Research Grant

UNKNOWN

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

FDA Office of Orphan Products Development

FED

Sponsor Role: collaborator

Sawa Ito, MD

OTHER

Sponsor Role: lead

Responsible Party

Sawa Ito, MD

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sawa M Ito, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Locations

Washington University

St Louis, Missouri, United States

Site Status: RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Linda Elias, RN

Role: CONTACT

eliaslj@upmc.edu

412-623-6037

Amy Rodger, RN

Role: CONTACT

rodgax@upmc.edu

412-623-4036

Facility Contacts

Ayan Gasanli, MBA

Role: primary

agasanli@wustl.edu

314-747-2449

Ryan Monahan, MBA

Role: backup

rmonahan@wustl.edu

314-454-8377

Linda Elias, RN

Role: primary

eliaslj@upmc.edu

412-623-6037

Amy Rodger, RN

Role: backup

rodgax@upmc.edu

412-623-4036

Elizabeth Frecker, B.S., SMB-A

Role: primary

efrecker@fredhutch.org

206-667-4129

Alisa Bradford

Role: backup

ajbradfo@fredhutch.org

206-667-2834

Other Identifiers

1R01FD008187-01

Identifier Type: FDA

Identifier Source: secondary_id

View Link

HCC 23-160

Identifier Type: -

Identifier Source: org_study_id