Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002)
Condition: Graft Versus Host Disease; Hematopoietic Stem Cell Transplantation; Leukemia
MeSH terms: Graft vs Host Disease
Intervention: Efprezimod alfa; Methotrexate; Tacrolimus; Placebo
Intervention description: Acute GVHD prophylaxis; Acute GVHD prophylaxis; Acute GVHD prophylaxis; 100 ml saline IV infusion.
Intervention MeSH terms: Methotrexate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Study was double blind for the first 6 participants in each arm. At that point, the recommended phase II dose (RP2D) was determined, and the selected arm enrolled additional participants in an open label fashion.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a multicenter prospective phase IIa dose escalation and phase IIa expansion cohort
      clinical trial designed to evaluate the safety and tolerability of efprezimod alfa for acute
      GVHD prophylaxis.
    

Eligibility criteria:

        Inclusion Criteria

        4.1.1 A prospective participant for allogeneic hematopoietic stem cell transplantation
        (HCT) for a malignant hematologic disorder.

        4.1.2 The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match
        at the HLA-A, -B, -C, and - DRB1 loci. High-resolution typing is required for all alleles
        for unmatched donors. Only matched unrelated donors are acceptable for this trial.

        4.1.3 The following diagnoses are to be included:

          1. Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or second
             remission. Remission is defined as the absence of blasts in the peripheral circulation
             at the time of enrollment, < 5% blasts in the bone marrow and absence of
             extramedullary disease including central nervous system (CNS) involvement.

          2. Chronic Myelogenous Leukemia (CML) in first or subsequent chronic phase failing to
             respond (or intolerant) to at least two different tyrosine kinase inhibitors. CML in
             accelerated or blast phase (CML-AP/BP) are eligible without requirement to fail
             tyrosine kinase inhibitor therapy, but must be in remission at time of enrollment.
             Remission is defined as the absence of blasts in the peripheral circulation at the
             time of enrollment, < 5% blasts in the bone marrow and absence of extramedullary
             disease including CNS involvement.

          3. Myelodysplastic syndrome (MDS) with intermediate or high-risk International Prognostic
             Scoring System (IPSS) or equivalent Revised IPSS (IPSS-R) score with < 10% blasts in
             the bone marrow.

          4. Chronic Myelomonocytic Leukemia (CMML) with < 10% blasts in the bone marrow.

        4.1.4 Males or non-pregnant, non-lactating females, ≥ 18 years of age. Note there is no
        defined upper age limited, so long as deemed appropriate candidate for myeloablative
        conditioning.

        4.1.5 Karnofsky Performance Status >70%.

        4.1.6 Participants must have normal or near normal organ function as defined by their
        treating institutions bone marrow transplantation (BMT) program clinical practice
        guidelines. In addition, for purposes of this protocol minimum organ function criteria
        within 21 days of beginning conditioning include:

        TABLE 1: Eligibility According to Pre HCT Organ Function Total bilirubin ≤2.5 mg% (unless
        from Gilbert's disease or disease-related) Aspartate aminotransferase (serum
        glutamic-oxaloacetic transaminase) (AST[SGOT])/ alanine aminotransferase (serum
        glutamic-pyruvic transaminase) (ALT[SGPT]) <3.0 X institutional upper limit of normal
        Estimated or actual glomerular filtration rate (GFR) >50 mL/min/1.73 m2 for participants
        with creatinine levels above institutional normal (GFR should be corrected for body surface
        area [BSA]) Pulmonary Function Tests* diffusing capacity of the lung for carbon monoxide
        (DLCO), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) > 50% DLCO
        should be corrected for hemoglobin Ejection Fraction* >50% Hematopoietic Cell
        Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5

        *May be assessed up to 6 weeks prior to the start of conditioning therapy

        4.1.7 Ability to understand and the willingness to sign a written informed consent
        document.

        4.1.8 Women of child bearing potential and men must agree to use contraception prior to
        study entry and through day 100 post HCT (hormonal or barrier method of birth control;
        abstinence). Should a woman become pregnant or suspect she is pregnant while she or her
        partner is on treatment in this study, she should inform her study physician immediately.
        Men treated or enrolled on this protocol must also agree to use adequate contraception
        prior to the study until day 100 post HCT.

        Exclusion Criteria:

        4.2.1 Participants may not have presence of active CNS disease or extramedullary disease.

        4.2.2 Prior cytotoxic chemotherapy within 21 days from the initiation of HCT conditioning
        (i.e. intensive induction / consolidation for AML). Note, certain low intensity treatments
        not intended to induce remission but rather stabilize disease are acceptable up to 24 hrs
        prior to initiation of HCT conditioning (i.e. Tyrosine Kinase Inhibitor, sorafenib).

        4.2.3 Cord blood and haploidentical donors are not eligible.

        4.2.4 HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are
        permissible.

        4.2.5 Pregnant and nursing mothers are excluded from this study. This is because the risk
        to the fetus is unknown.

        4.2.6 Any physical or psychological condition that, in the opinion of the investigator,
        would pose unacceptable risk to the participant or raise concern that the participant would
        not comply with protocol procedures.

        4.2.7 Uncontrolled infections. Participants still under therapy for presumed or proven
        infection are eligible provided there is clear evidence (radiologic, clinical and/or
        culture) that the infection is well controlled.

        4.2.8 Participants seropositive or polymerase chain reaction (PCR) positive for the human
        immunodeficiency virus (HIV). Participants with evidence of Hepatitis B or Hepatitis C PCR
        positivity.

        4.2.9 Prior HCT (allograft or prior autograft).

        4.2.10 Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin
        [ATG], alemtuzumab) is prohibited.

        4.2.11 Current or prior diagnosis of antecedent Myelofibrosis is excluded.