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)

NCT04095858 | Terminated Phase 3 Results DMC FDA Drug

• 5 other identifiers: 7110-00515-4789FD-OOPD-006089CD24Fc-005MK-7110-005
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Hematopoietic Stem Cell Transplantation; Acute Graft Versus Host Disease; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 180 Day Grade III-IV Acute Graft-Versus-Host Disease (GVHD)-Free Survival (aGFS)

  Grade III-IV aGFS was defined as the time in days to the earlier of the first documented acute Grade III-IV GVHD or death by any cause in 180 days after hematopoietic stem cell transplantation (HCT). Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Participants who did not drop out or experience aGVHD or death were censored at the time of leukemia relapse or Day 180, whichever came first.

  Up to 180 days after HCT

Secondary Outcomes (4)

• Overall Survival (OS)

  Up to 180 days after HCT

• Disease Free Survival (DFS)

  Up to 180 days after HCT

• 180 Day Grade II-IV aGFS

  Up to 180 days after HCT

• 180 Day Grade III-IV aGVHD-free and Relapse-free Survival (aGVHD RFS)

  Up to 180 days after HCT

Study Arms (2)

Efprezimod alfa Treatment

EXPERIMENTAL

Efprezimod alfa: IV infusion, 480 mg (day -1), 240 mg (day +14) and 240 mg (day +28); Tacrolimus: begin on day -3. IV \[0.03 mg/kg/day\] or by mouth (PO) \[0.045 mg/kg/dose\] dosing is permitted; Methotrexate: given IV at a dose of 15 mg/m\^2/dose once daily on Day 1 after hematopoietic cell transplantation (HCT), and at a dose of 10 mg/m\^2/dose on days 3, 6, and 11 after HCT.

Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus

Placebo

PLACEBO COMPARATOR

Placebo (Saline solution): 100 ml IV infusion, Day -1, Day 14, Day 28. Tacrolimus: begin on day -3. IV \[0.03mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted; Methotrexate: given IV at a dose of 15 mg/m\^2/dose once daily on Day 1 after HCT, and at a dose of 10 mg/m\^2/dose on days 3, 6, and 11 after HCT.

Drug: Placebo; Drug: Methotrexate; Drug: Tacrolimus

Interventions

Efprezimod alfa DRUG

IV infusion: 480 mg at Day -1, 240 mg at Day 14, 240 mg at Day 28.

Also known as: Human CD24 and human IgG Fc Fusion Protein, MK-7110

Efprezimod alfa Treatment

Placebo DRUG

IV infusion, 100 ml at Day -1, Day 14, and Day 28.

Also known as: Saline

Placebo

Methotrexate DRUG

IV, 15 mg/m\^2/dose at Day 1, then 10 mg/m2/dose at Day 3, 6, 11.

Also known as: Trexall

Efprezimod alfa Treatment; Placebo

Tacrolimus DRUG

Begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted

Also known as: FK506, Prograf

Efprezimod alfa Treatment; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A prospective participant for allogeneic HCT for a malignant hematologic disorder.
• 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.
• The following diagnoses are to be included:
• 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.
• 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.
• 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.
• Karnofsky Performance Status \>70%.
• 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:
• Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related);
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT))/ alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) \<5.0 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 BSA);
• 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;
• Ejection Fraction \>50%;
• 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.

You may not qualify if:

• Subjects may not have presence of active central nervous system (CNS) disease or extramedullary disease.
• 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).
• Cord blood and haploidentical donors are not eligible.
• HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are permissible.
• Pregnant and nursing mothers are excluded from this study. This is because the risk to the fetus is unknown.
• 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.
• 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.
• 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.
• Prior HCT (allograft or prior autograft).
• Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin (ATG), alemtuzumab) is prohibited.
• Current or prior diagnosis of antecedent Myelofibrosis is excluded.

Sponsors & Collaborators

• Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (4)

City of Hope ( Site 0302)

Duarte, California, 91010, United States

Location

The University of Chicago Medical Center ( Site 0306)

Chicago, Illinois, 60637, United States

Location

Penn State University Milton S. Hershey Medical Center ( Site 0304)

Hershey, Pennsylvania, 17033, United States

Location

Abramson Cancer Center of the University of Pennsylvania ( Site 0309)

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Interventions

Sodium Chloride; Methotrexate; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 19, 2019
• Study Start: January 5, 2021
• Primary Completion: November 5, 2021
• Study Completion: November 5, 2021
• Last Updated: February 8, 2023
• Results First Posted: November 14, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4)