Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft Versus Host Disease (GVHD) Following Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-005)
Condition: Hematopoietic Stem Cell Transplantation; Acute Graft Versus Host Disease; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Graft vs Host Disease
Intervention: Efprezimod alfa; Placebo; Methotrexate; Tacrolimus
Intervention description: IV infusion: 480 mg at Day -1, 240 mg at Day 14, 240 mg at Day 28.; IV infusion, 100 ml at Day -1, Day 14, and Day 28.; IV, 15 mg/m^2/dose at Day 1, then 10 mg/m2/dose at Day 3, 6, 11.; Begin on day -3. IV [0.03 mg/kg/day] or PO [0.045 mg/kg/dose] dosing is permitted
Intervention MeSH terms: Methotrexate; Tacrolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens:
      efprezimod alfa vs placebo with the standard GVHD prophylaxis of tacrolimus / methotrexate.

      The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens:
      efprezimod alfa/tacrolimus / methotrexate (efprezimod alfa/Tac/MTX) versus placebo/tacrolimus
      / methotrexate (placebo/Tac/MTX) in the setting of myeloablative conditioning (MAC), matched
      unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation in participants with
      acute leukemia (AML/ALL) or myelodysplastic syndrome (MDS). The study agent, efprezimod alfa,
      will be administered through IV infusion on days -1, 14, and 28 at the dose of 480mg, 240 mg
      and 240mg, respectively. The placebo will be 100 ml normal saline intravenous (IV) solution.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A prospective participant for allogeneic HCT for a malignant hematologic disorder.

          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.

          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 CNS involvement.

               2. Myelodysplastic syndrome (MDS) with intermediate or high-risk International
                  Prognostic Scoring System (IPSS) or equivalent Revised International Prognostic
                  Scoring System (IPSS-R) score with < 10% blasts in the bone marrow.

          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.

          5. Karnofsky Performance Status >70%.

          6. Participants must have normal or near normal organ function as defined by their
             treating institutions bone marrow transplant (BMT) program clinical practice
             guidelines. In addition, for purposes of this protocol minimum organ function criteria
             within 30 days of beginning conditioning include: Eligibility According to Pre HCT
             Organ Function:

               1. Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related);

               2. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
                  (SGOT))/ alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase
                  (SGPT)) <5.0 X institutional upper limit of normal;

               3. 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 BSA);

               4. Pulmonary Function Tests include diffusing capacity of the lungs for carbon
                  monoxide (DLCO), forced expiratory volume in one second (FEV1), forced vital
                  capacity (FVC)> 50% DLCO should be corrected for hemoglobin;

               5. Ejection Fraction >50%;

               6. Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5.

             Item d and e may be assessed up to 10 weeks prior to the start of conditioning
             therapy.

          7. Ability to understand and the willingness to sign a written informed consent document.

          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:

          1. Subjects may not have presence of active central nervous system (CNS) disease or
             extramedullary disease.

          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).

          3. Cord blood and haploidentical donors are not eligible.

          4. HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are
             permissible.

          5. Pregnant and nursing mothers are excluded from this study. This is because the risk to
             the fetus is unknown.

          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.

          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.

          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.

          9. Prior HCT (allograft or prior autograft).

         10. Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin (ATG),
             alemtuzumab) is prohibited.

         11. Current or prior diagnosis of antecedent Myelofibrosis is excluded.