A Randomized, Double Blind, Placebo Controlled, Multi-center, Phase III Study of CD24Fc for Prevention of Acute Graft-Versus-Host Disease Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Overview
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Enrollment
- 11
- Locations
- 4
- Primary Endpoint
- 180 Day Grade III-IV Acute Graft-Versus-Host Disease (GVHD)-Free Survival (aGFS)
Overview
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.
Detailed Description
The Sponsor decided to discontinue screening and enrollment in this study on 18 May 2021 for business reasons. This decision was not related to any new or unexpected safety or efficacy findings.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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;
Exclusion Criteria
- •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.
Arms & Interventions
Placebo
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.
Intervention: Placebo (Drug)
Efprezimod alfa Treatment
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.
Intervention: Efprezimod alfa (Drug)
Efprezimod alfa Treatment
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.
Intervention: Methotrexate (Drug)
Efprezimod alfa Treatment
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.
Intervention: Tacrolimus (Drug)
Placebo
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.
Intervention: Methotrexate (Drug)
Placebo
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.
Intervention: Tacrolimus (Drug)
Outcomes
Primary Outcomes
180 Day Grade III-IV Acute Graft-Versus-Host Disease (GVHD)-Free Survival (aGFS)
Time Frame: Up to 180 days after HCT
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.
Secondary Outcomes
- Overall Survival (OS)(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)
- Disease Free Survival (DFS)(Up to 180 days after HCT)