Graft Versus Host DiseasePhase 2NCT02663622
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)
A Phase 2 study testing Efprezimod alfa, Methotrexate and Tacrolimus in people with Graft Versus Host Disease and Hematopoietic Stem Cell Transplantation, run by Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia
- What is being tested?
- Efprezimod alfa, Methotrexate and Tacrolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 4 sitesUnited States
- Study dates
- 19 Sep 2016to 18 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- 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.
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Ohio State University
Columbus, Ohio, 43210
Karmanos Cancer Institute
Detroit, Michigan, 48201
Indiana University School of Medicine
Indianapolis, Indiana, 46202
About this study
Official title: A Phase II Trial of CD24Fc for Prevention of Acute Graft-versus-Host Disease Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplant
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.
Read the detailed description
The first part of this study was a phase IIa randomized, double blind, placebo controlled, multi-center study to investigate adding efprezimod alfa to standard of care tacrolimus and methotrexate in acute graft-versus host disease (GVHD) prophylaxis for allogeneic hematopoietic stem cell transplantation (HCT) with matched unrelated donors in treatment of leukemia and myelodysplastic syndrome. The primary objective was to evaluate the safety, tolerability and dose-limiting toxicities (DLTs) of efprezimod alfa in participants undergoing matched unrelated donor myeloablative allogeneic HCT for malignant hematologic disorders. Three dose cohorts were planned with 240 mg at day -1 (one day prior to HCT), 480 mg at day -1, and the multi-dose cohort of 480-240-240 mg at day -1, day 14 and day 28. The efprezimod alfa : placebo randomization ratio was 3:1.
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.
- Being tested
- Efprezimod alfa, Methotrexate, Tacrolimus, Placebo
- Medical subject headings
- Graft vs Host Disease, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efprezimod alfaDrug
Also called CD24 Fusion Protein, MK-7110
Acute GVHD prophylaxis
MethotrexateDrug
Also called Trexall
Acute GVHD prophylaxis
TacrolimusDrug
Also called FK506, Prograf
Acute GVHD prophylaxis
PlaceboDrug
Also called Saline Solution
100 ml saline IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Efprezimod alfa 240 mg | Experimental | 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) Receives: Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus |
| Efprezimod alfa 480 mg | Experimental | 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) Receives: Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus |
| Efprezimod alfa 960 mg | Experimental | 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) Receives: Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus |
| Placebo | Placebo comparator | 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) Receives: Drug: Methotrexate; Drug: Tacrolimus; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. As described in the protocol, AEs reported after the protocol-specified timeframe were not analyzed in this outcome measure: 1 day prior to hematopoietic stem cell transplantation (HCT) through either 30 or 60 days post-HCT, depending on arm as defined in the Time Frame section.
Measured: Up to approximately 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 62 days for the CD24Fc 960 mg arm.
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.
Measured: 1 day for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 30 days for the CD24Fc 960 mg arm.
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
A DLT was defined as: any Grade III or higher non-hematologic toxicity not clearly related to the underlying malignancy, intercurrent infection, or the hematopoietic stem cell transplantation conditioning regimen; any death not related to relapse or intercurrent infection; and failure to engraft by day 30. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Hypersensitivity reactions and other infusion-related reactions were not considered DLTs.
Measured: Up to 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 62 days for the CD24Fc 960 mg arm.
Open Label Expansion Arm Only: Grade III-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS)
AGFS was defined as the time from the date of hematopoietic stem cell transplantation (HCT) to the earliest of Grade III-IV acute GVHD or death due to any cause, whichever occurred first. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Participants were censored at 181 days.
Measured: Up to 181 days
Secondary outcomes (9)
Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS)
AGFS was defined as the time from the date of hematopoietic stem cell transplantation (HCT) to the earliest of Grade II-IV acute GVHD or death due to any cause, whichever occurred first. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Participants were censored at 195 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms, and at 181 days for the CD24Fc 960 mg arm.
Measured: Up to 195 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 181 days for the CD24Fc 960 mg arm.
Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT
The percentage of participants who experienced grade II to IV acute GVHD is presented as cumulative incidence of Grade II to IV acute GVHD by approximately 108 days following HCT. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. The cumulative incidence (%) of acute GVHD and the 95% CI were estimated using the cumulative incidence function with death without Grade II to IV acute GVHD as a competing risk.
Measured: Up to approximately 108 days
Percentage of Participants Experiencing Chronic GVHD Following HCT
The percentage of participants who experienced chronic GVHD will be presented as cumulative incidence of chronic GVHD. Chronic GVHD assessments occurred approximately quarterly beginning on Day 100 after HCT until 1 year after HCT. The cumulative incidence (%) of chronic GVHD at 1 year post-HCT and the 95% CI were estimated using the cumulative incidence function with death without chronic GVHD as a competing risk. If the maximum observed time was <Study Day 380, the cumulative incidence at the maximum observed time is presented for a treatment group.
Measured: Up to 380 days
Percentage of Participants Experiencing Relapse Following HCT
The percentage of participants who experienced relapse of disease is presented as cumulative incidence of relapse. The cumulative incidence (%) of relapse at approximately 1 year following HCT and the 95% CI were estimated using the cumulative incidence function with death without relapse as a competing risk. If the maximum observed time is < Study Day 380, the cumulative incidence at the maximum observed time is presented.
Measured: Up to 380 days
Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT
The percentage of participants who experienced NRM is presented as cumulative incidence of NRM. The cumulative incidence (%) of NRM at approximately 1 year following HCT and the 95% CI were estimated using the cumulative incidence function with relapse as a competing risk. If the maximum observed time is < Study Day 380, the cumulative incidence at the maximum observed time will be presented.
Measured: Up to 380 days
Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT)
The percentage of participants who experienced infection by approximately 101 days following HCT is presented.
Measured: Up to approximately 101 days
Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT)
OS is defined as the time from HCT to death due to any cause. Participants were censored at 380 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms, and at 366 days for the CD24Fc 960 mg arm.
Measured: Up to 380 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 366 days for the CD24Fc 960 mg arm.
GVHD-Free and Relapse-Free Survival (GRFS) Following HCT
This GRFS following HCT is a composite endpoint in which events included Grade III to IV acute GVHD, chronic GVHD requiring systemic immunosuppressive therapy, relapse, or death from any cause
Measured: Up to 380 days
Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT)
RFS is defined as the time from HCT to relapse or death due to any cause. Participants were censored at 380 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms, and at 366 days for the CD24Fc 960 mg arm.
Measured: Up to 380 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 366 days for the CD24Fc 960 mg arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study start19 Sep 2016
- Primary completion8 Jun 2020
- Study completion18 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ohio State University, University of Michigan Rogel Cancer Center, Indiana University, Barbara Ann Karmanos Cancer Institute, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663622
- Sponsor's protocol ID
- 7110-002
- Other IDs
- HUM00107805, 15-4789, R44CA221513, R44CA246991, UMCC 2015.181, MK-7110-002, NCI-2017-00017, CD24Fc-002
- Status last verified
- Jan 2024
- First submitted
- 21 Jan 2016
- Last updated
- 23 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 28724800Toubai 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.
PubMed 24695850Toubai 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.
PubMed 27965667Magenau 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.
PubMed 37647633
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of CD24Fc for Prevention of Acute Graft-versus-Host Disease Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT02663622
- Acronym / sponsor ID
- 7110-002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Collaborators
- Ohio State University, University of Michigan Rogel Cancer Center, Indiana University, Barbara Ann Karmanos Cancer Institute, National Cancer Institute (NCI)
- Study start
- 19 Sep 2016 (actual)
- Primary completion
- 8 Jun 2020 (actual)
- Study completion
- 18 May 2021 (actual)
- First posted
- 26 Jan 2016 (estimated)
- Results
- Posted 18 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The first part of this study was a phase IIa randomized, double blind, placebo controlled, multi-center study to investigate adding efprezimod alfa to standard of care tacrolimus and methotrexate in acute graft-versus host disease (GVHD) prophylaxis for allogeneic hematopoietic stem cell transplantation (HCT) with matched unrelated donors in treatment of leukemia and myelodysplastic syndrome. The primary objective was to evaluate the safety, tolerability and dose-limiting toxicities (DLTs) of efprezimod alfa in participants undergoing matched unrelated donor myeloablative allogeneic HCT for malignant hematologic disorders. Three dose cohorts were planned with 240 mg at day -1 (one day prior to HCT), 480 mg at day -1, and the multi-dose cohort of 480-240-240 mg at day -1, day 14 and day 28. The efprezimod alfa : placebo randomization ratio was 3:1.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Efprezimod alfa 240 mg | Experimental | Drug: Efprezimod alfa, Drug: Methotrexate, Drug: TacrolimusEfprezimod 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 480 mg | Experimental | Drug: Efprezimod alfa, Drug: Methotrexate, Drug: TacrolimusEfprezimod 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 960 mg | Experimental | Drug: Efprezimod alfa, Drug: Methotrexate, Drug: TacrolimusEfprezimod 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) |
| Placebo | Placebo comparator | Drug: Methotrexate, Drug: Tacrolimus, Drug: PlaceboPlacebo 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- 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.
- 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.
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efprezimod alfaAlso: CD24 Fusion Protein, MK-7110Acute GVHD prophylaxis | Drug | Efprezimod alfa 240 mg, Efprezimod alfa 480 mg, Efprezimod alfa 960 mg |
| MethotrexateAlso: TrexallAcute GVHD prophylaxis | Drug | Efprezimod alfa 240 mg, Efprezimod alfa 480 mg, Efprezimod alfa 960 mg, Placebo |
| TacrolimusAlso: FK506, PrografAcute GVHD prophylaxis | Drug | Efprezimod alfa 240 mg, Efprezimod alfa 480 mg, Efprezimod alfa 960 mg, Placebo |
| PlaceboAlso: Saline Solution100 ml saline IV infusion. | Drug | Placebo |
Primary outcome
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 62 days for the CD24Fc 960 mg arm.
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. As described in the protocol, AEs reported after the protocol-specified timeframe were not analyzed in this outcome measure: 1 day prior to hematopoietic stem cell transplantation (HCT) through either 30 or 60 days post-HCT, depending on arm as defined in the Time Frame section.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: 1 day for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 30 days for the CD24Fc 960 mg arm.
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
Time frame: Up to 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 62 days for the CD24Fc 960 mg arm.
A DLT was defined as: any Grade III or higher non-hematologic toxicity not clearly related to the underlying malignancy, intercurrent infection, or the hematopoietic stem cell transplantation conditioning regimen; any death not related to relapse or intercurrent infection; and failure to engraft by day 30. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Hypersensitivity reactions and other infusion-related reactions were not considered DLTs.
Open Label Expansion Arm Only: Grade III-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS)
Time frame: Up to 181 days
AGFS was defined as the time from the date of hematopoietic stem cell transplantation (HCT) to the earliest of Grade III-IV acute GVHD or death due to any cause, whichever occurred first. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Participants were censored at 181 days.
9 secondary outcomes
Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS)
Time frame: Up to 195 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 181 days for the CD24Fc 960 mg arm.
Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT
Time frame: Up to approximately 108 days
Percentage of Participants Experiencing Chronic GVHD Following HCT
Time frame: Up to 380 days
Percentage of Participants Experiencing Relapse Following HCT
Time frame: Up to 380 days
Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT
Time frame: Up to 380 days
Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT)
Time frame: Up to approximately 101 days
Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT)
Time frame: Up to 380 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 366 days for the CD24Fc 960 mg arm.
GVHD-Free and Relapse-Free Survival (GRFS) Following HCT
Time frame: Up to 380 days
Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT)
Time frame: Up to 380 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 366 days for the CD24Fc 960 mg arm
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28724800Toubai 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.
- Background: PubMed 24695850Toubai 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.
- Background: PubMed 27965667Toubai 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.
- Results publication: PubMed 37647633Magenau 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.
- Merck Oncology Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Related trials for Graft Versus Host Disease
Active, not recruitingPhase 2
De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis
Graft-versus-host Disease
RecruitingEarly Phase 1
HMCT/CT2401: Abatacept GVHD Prophylaxis Following Omidubicel HCT
Hematologic Malignancy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
RecruitingPhase 1/2
The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning and Peripheral Blood Stem Cell Transplantation
Peripheral Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation
RecruitingPhase 1/2
Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Efprezimod alfa, Methotrexate and Tacrolimus in people with Graft Versus Host Disease and Hematopoietic Stem Cell Transplantation, run by Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced an Adverse Event (AE) (time frame: Up to approximately 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 62 days for the CD24Fc 960 mg arm.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02663622, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.