Myelodysplastic SyndromesEarly Phase 1NCT04628338
IFN-γ to Treat Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) That Has Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation
A Early Phase 1 study testing IFN-γ (interferon gamma-1b) injection in people with Myelodysplastic Syndromes and Myeloid Leukemia, run by Sawa Ito, MD at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Myeloid Leukemia, Allogeneic Stem Cell Transplantation
- What is being tested?
- IFN-γ (interferon gamma-1b) injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2021to 30 Oct 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Pilot Study of IFN-γ to Treat Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) That Has Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation
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.
Read the 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.
- Being tested
- IFN-γ (interferon gamma-1b) injection
- 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
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IFN-γ (interferon gamma-1b) injectionDrug
Also called ACTIMMUNE®
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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: IFN-γ (interferon gamma-1b) injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 6 months
Adverse events related to IFN-γ
Adverse events of IFN-γ in relapsed patients after alloSCT per CTCAE v5.0.
Measured: 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.
Measured: Up to 6 months
Secondary outcomes (3)
Malignant Blast Burden
Change in malignant blasts number after IFN-γ therapy and subsequent donor lymphocyte infusion.
Measured: Up to 6 months
Incidence of GVHD
Incidence of Graft Versus Host Disease (GVHD) progression or de novo GVHD after INF-g therapy and subsequent donor lymphocyte infusion.
Measured: Up to 6 months
Incidence of de novo GVHD
Incidence of graft-versus-host disease (GVHD) progression after IFN-γ therapy and subsequent DLI.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2020
- Study start8 Mar 2021
- Primary completion30 Oct 2023
- Study completion30 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sawa Ito, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Horizon Pharma USA, Inc.
- Responsible party
- Sponsor-investigator, Sawa Ito, MD, University of Pittsburgh
- Investigators
- Sawa Ito, MD; PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04628338
- Sponsor's protocol ID
- HCC 20-092
- Status last verified
- Apr 2025
- First submitted
- 29 Oct 2020
- Last updated
- 29 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40131369
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of IFN-γ to Treat Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) That Has Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT04628338
- Acronym / sponsor ID
- HCC 20-092
- Keywords
- allogeneic hematopoietic stem cell transplantation, acute myeloid leukemia, myelodysplastic syndrome, graft versus host disease, AML, MDS, alloSCT, GVHD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Sawa Ito, MDUniversity, hospital or other
- Collaborators
- Horizon Pharma USA, Inc.
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 30 Oct 2023 (actual)
- Study completion
- 30 Oct 2023 (actual)
- First posted
- 13 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IFN-γ | Experimental | Drug: IFN-γ (interferon gamma-1b) injection100mcg 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IFN-γ (interferon gamma-1b) injectionAlso: ACTIMMUNE®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) | Drug | IFN-γ |
Primary outcome
Upregulation HLA l (HLA-ABC)
Time frame: Up to 6 months
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.
Upregulation of HLA ll (HLA-DR/DQ)
Time frame: Up to 6 months
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.
Upregulation of ICAM-1
Time frame: Up to 6 months
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.
Adverse events related to IFN-γ
Time frame: Up to 6 months
Adverse events of IFN-γ in relapsed patients after alloSCT per CTCAE v5.0.
Generation of phosphorylated-STAT1
Time frame: Up to 6 months
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.
3 secondary outcomes
Malignant Blast Burden
Time frame: Up to 6 months
Incidence of GVHD
Time frame: Up to 6 months
Incidence of de novo GVHD
Time frame: Up to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Background: PubMed 40131369Ito 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.
- IFN-γand donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation - PubMedLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sawa Ito, MD; PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing IFN-γ (interferon gamma-1b) injection in people with Myelodysplastic Syndromes and Myeloid Leukemia, run by Sawa Ito, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Upregulation HLA l (HLA-ABC) (time frame: Up to 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04628338, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.