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)
NCT ID: NCT02663622
Last Updated: 2024-01-23
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
44 participants
INTERVENTIONAL
2016-09-19
2021-05-18
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
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
PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic Transplant
NCT03699631
Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
NCT00224874
Acute Graft-versus-Host Disease Treatment (BMT CTN 0802)
NCT01002742
Study of Gecacitinib-corticosteroid as First-line Therapy for Grade II-IV Acute Graft Versus Host Disease
NCT07185633
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The second part was a prospective open label phase IIa expansion cohort trial investigating the addition of efprezimod alfa to standard acute graft-versus host disease (GVHD) prophylaxis for allogeneic hematopoietic stem cell transplantation (HCT). Based on the first part's safety results and the pharmacokinetic data, the phase IIa expansion dose was the multi-dose 480-240-240 mg regimen administered on day -1, day 14 and day 28, respectively. The primary objective of phase IIa expansion was to determine if the addition of efprezimod alfa to standard GVHD prophylaxis improves 180 days post-HCT grade III-IV acute GVHD-free survival (AGFS) when compared to Center for International Blood and Marrow Transplant Research (CIBMTR) database registered control participants who had standard GVHD prophylaxis alone. Eligible participants were those requiring allogeneic HCT for malignant hematologic conditions and receiving a myeloablative conditioning regimen.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Efprezimod alfa 240 mg
Efprezimod alfa in 240 mg as intravenous (IV) infusion at Day -1 + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)
Efprezimod alfa
Acute GVHD prophylaxis
Methotrexate
Acute GVHD prophylaxis
Tacrolimus
Acute GVHD prophylaxis
Efprezimod alfa 480 mg
Efprezimod alfa in 480 mg as intravenous (IV) infusion at Day -1 + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)
Efprezimod alfa
Acute GVHD prophylaxis
Methotrexate
Acute GVHD prophylaxis
Tacrolimus
Acute GVHD prophylaxis
Efprezimod alfa 960 mg
Efprezimod alfa (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 PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)
Efprezimod alfa
Acute GVHD prophylaxis
Methotrexate
Acute GVHD prophylaxis
Tacrolimus
Acute GVHD prophylaxis
Placebo
Placebo to efprezimod alfa (saline IV injection solution) on day -1 or days -1, 14, and 28 + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)
Methotrexate
Acute GVHD prophylaxis
Tacrolimus
Acute GVHD prophylaxis
Placebo
100 ml saline IV infusion.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Efprezimod alfa
Acute GVHD prophylaxis
Methotrexate
Acute GVHD prophylaxis
Tacrolimus
Acute GVHD prophylaxis
Placebo
100 ml saline IV infusion.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
4.2.2 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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Ohio State University
OTHER
University of Michigan Rogel Cancer Center
OTHER
Indiana University School of Medicine
OTHER
Barbara Ann Karmanos Cancer Institute
OTHER
National Cancer Institute (NCI)
NIH
Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Indiana University School of Medicine
Indianapolis, Indiana, United States
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Ohio State University
Columbus, Ohio, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Toubai T, Rossi C, Oravecz-Wilson K, Zajac C, Liu C, Braun T, Fujiwara H, Wu J, Sun Y, Brabbs S, Tamaki H, Magenau J, Zheng P, Liu Y, Reddy P. Siglec-G represses DAMP-mediated effects on T cells. JCI Insight. 2017 Jul 20;2(14):e92293. doi: 10.1172/jci.insight.92293. eCollection 2017 Jul 20.
Toubai T, Hou G, Mathewson N, Liu C, Wang Y, Oravecz-Wilson K, Cummings E, Rossi C, Evers R, Sun Y, Wu J, Choi SW, Fang D, Zheng P, Liu Y, Reddy P. Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice. Blood. 2014 May 29;123(22):3512-23. doi: 10.1182/blood-2013-12-545335. Epub 2014 Apr 2.
Toubai T, Mathewson ND, Magenau J, Reddy P. Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives. Front Immunol. 2016 Nov 29;7:539. doi: 10.3389/fimmu.2016.00539. eCollection 2016.
Magenau J, Jaglowski S, Uberti J, Farag SS, Riwes MM, Pawarode A, Anand S, Ghosh M, Maciejewski J, Braun T, Devenport M, Lu S, Banerjee B, DaSilva C, Devine S, Zhang MJ, Burns LJ, Liu Y, Zheng P, Reddy P. A phase 2 trial of CD24Fc for prevention of graft-versus-host disease. Blood. 2024 Jan 4;143(1):21-31. doi: 10.1182/blood.2023020250.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
Merck Oncology Clinical Trials Information
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
HUM00107805
Identifier Type: OTHER
Identifier Source: secondary_id
15-4789
Identifier Type: OTHER
Identifier Source: secondary_id
UMCC 2015.181
Identifier Type: OTHER
Identifier Source: secondary_id
MK-7110-002
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2017-00017
Identifier Type: OTHER
Identifier Source: secondary_id
CD24Fc-002
Identifier Type: OTHER
Identifier Source: secondary_id
7110-002
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.