RECRUITING

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

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes interferon-γ (IFN-γ)donor leukocyte infusion (DLI)allogeneic hematopoietic stem cell transplantation (alloSCT)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 2 Trial of Interferon-γ (IFN-γ) in Combination With Donor Leukocyte Infusion (DLI) to Treat Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) After Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT)

Quick Facts

Study Start:2024-08-22

Study Completion:2027-10-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06529731

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Recipients of an alloSCT for AML or MDS from an HLA-matched donor * AML/MDS relapsed post-alloSCT with measurable residual disease defined by at least 5% of more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2 * A DLI is available, or the donor is available and agrees to undergo apheresis to collect lymphocytes for infusion * If salvage therapy for post-alloSCT relapse was received, the therapy is limited to 1 cycle 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 * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * 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 * 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	* Primary engraftment failure after alloSCT * Grade 3 or 4 aGVHD per Mount Sinai Acute GVHD International Consortium (MAGIC) at the time of planned enrollment * History of grade 4 aGVHD per the MAGIC criteria * Moderate or severe cGVHD per NIH Consensus Criteria at time of planned enrollment * Any systemic immunosuppressive medications taken within 2 weeks before the enrollment * Grade 3 or higher non-hematologic toxicity related to any prior therapy at the time of enrollment * A contraindication to receive IFN-γ including a known hypersensitivity to IFN-γ, E. coli derived products or any other component of the product * Positive pregnancy test or currently breastfeeding on Day 1 of study treatment * 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 * Active ischemic heart disease not controlled with medications within 2 months of enrollment * Acute or chronic pulmonary disease requiring continuous oxygen treatment * Seizure disorder not controlled by medications within 2 months of enrollment * AST or ALT \> 5x ULN or total bilirubin \>3x ULN at time of enrollment * Renal function eGFR \<30 mL/min at time of enrollment using modified Cockcroft-Gault formula * 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

Inclusion Criteria

Exclusion Criteria

* Recipients of an alloSCT for AML or MDS from an HLA-matched donor
* AML/MDS relapsed post-alloSCT with measurable residual disease defined by at least 5% of more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
* A DLI is available, or the donor is available and agrees to undergo apheresis to collect lymphocytes for infusion
* If salvage therapy for post-alloSCT relapse was received, the therapy is limited to 1 cycle 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
* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* 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
* 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

* Primary engraftment failure after alloSCT
* Grade 3 or 4 aGVHD per Mount Sinai Acute GVHD International Consortium (MAGIC) at the time of planned enrollment
* History of grade 4 aGVHD per the MAGIC criteria
* Moderate or severe cGVHD per NIH Consensus Criteria at time of planned enrollment
* Any systemic immunosuppressive medications taken within 2 weeks before the enrollment
* Grade 3 or higher non-hematologic toxicity related to any prior therapy at the time of enrollment
* A contraindication to receive IFN-γ including a known hypersensitivity to IFN-γ, E. coli derived products or any other component of the product
* Positive pregnancy test or currently breastfeeding on Day 1 of study treatment
* 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
* Active ischemic heart disease not controlled with medications within 2 months of enrollment
* Acute or chronic pulmonary disease requiring continuous oxygen treatment
* Seizure disorder not controlled by medications within 2 months of enrollment
* AST or ALT \> 5x ULN or total bilirubin \>3x ULN at time of enrollment
* Renal function eGFR \<30 mL/min at time of enrollment using modified Cockcroft-Gault formula
* 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

Contacts and Locations

Study Contact

Linda Elias, RN

CONTACT

412-623-6037

eliaslj@upmc.edu

Amy Rodger, RN

CONTACT

412-623-4036

rodgax@upmc.edu

Principal Investigator

Sawa M Ito, MD, PhD

PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Study Locations (Sites)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Collaborators and Investigators

Sponsor: Sawa Ito, MD

Sawa M Ito, MD, PhD, PRINCIPAL_INVESTIGATOR, UPMC Hillman Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-22

Study Completion Date2027-10-31

Study Record Updates

Study Start Date2024-08-22

Study Completion Date2027-10-31

Terms related to this study

Keywords Provided by Researchers

interferon-γ (IFN-γ)
donor leukocyte infusion (DLI)
allogeneic hematopoietic stem cell transplantation (alloSCT)

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Myelodysplastic Syndromes