Clinical Trials /

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

NCT04628338

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: HCC 20-092
  • NCT ID: NCT04628338

Conditions

  • Myelodysplastic Syndromes
  • Myeloid Leukemia
  • Allogeneic Stem Cell Transplantation

Interventions

DrugSynonymsArms
IFN-γ (interferon gamma-1b) injectionACTIMMUNE®IFN-γ

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
IFN-γExperimental100mcg IFN-γ subcutaneously three times per week (Weeks 0-7), once per week (Weeks 8-12)
  • IFN-γ (interferon gamma-1b) injection

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Upregulation HLA l (HLA-ABC)
Time Frame:Up to 6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Malignant Blast Burden
Time Frame:Up to 6 months
Safety Issue:
Description:Change in malignant blasts number after IFN-γ therapy and subsequent donor lymphocyte infusion.
Measure:Incidence of GVHD
Time Frame:Up to 6 months
Safety Issue:
Description:Incidence of Graft Versus Host Disease (GVHD) progression or de novo GVHD after INF-g therapy and subsequent donor lymphocyte infusion.
Measure:Incidence of de novo GVHD
Time Frame:Up to 6 months
Safety Issue:
Description:Incidence of graft-versus-host disease (GVHD) progression after IFN-γ therapy and subsequent DLI.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sawa Ito, MD

Trial 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

Last Updated

November 13, 2020