Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia
Conditions
Brief 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.
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.
Interventions
DRUGEfprezimod alfa
Acute GVHD prophylaxis
DRUGMethotrexate
Acute GVHD prophylaxis
DRUGTacrolimus
Acute GVHD prophylaxis
DRUGPlacebo
100 ml saline IV infusion.
Sponsors
Ohio State University
University of Michigan Rogel Cancer Center
Indiana University School of Medicine
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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: 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
4.2.1 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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | 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 | 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) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT | Up to 380 days | 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. |
| Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT) | Up to approximately 101 days | The percentage of participants who experienced infection by approximately 101 days following HCT is presented. |
| Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) | 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. | 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. |
| GVHD-Free and Relapse-Free Survival (GRFS) Following HCT | Up to 380 days | 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 |
| Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT) | 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 | 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. |
| Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT) | 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. | 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. |
| Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT | Up to approximately 108 days | 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. |
| Percentage of Participants Experiencing Chronic GVHD Following HCT | Up to 380 days | 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. |
| Percentage of Participants Experiencing Relapse Following HCT | Up to 380 days | 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. |
Countries
United States
Participant flow
Pre-assignment details
The CD24Fc 960 mg arm was initiated alongside the other 3 arms. Once the recommended phase 2 dose (RP2D) was determined, the other 3 arms ceased recruitment but additional participants were recruited into the CD24Fc 960 mg arm. Per FDA request, all participants in the CD24Fc 960 mg arm are considered a single population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo to CD24Fc (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) | 6 |
| CD24Fc 240 mg CD24Fc 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) | 6 |
| CD24Fc 480 mg CD24Fc 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) | 6 |
| CD24Fc 960 mg CD24Fc (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) | 26 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 1 | 8 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | CD24Fc 960 mg | Total | Placebo | CD24Fc 240 mg | CD24Fc 480 mg |
|---|---|---|---|---|---|
| Age, Customized 18-29 years of age | 3 Participants | 6 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Customized 30-39 years of age | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Customized 40-49 years of age | 4 Participants | 6 Participants | 1 Participants | 1 Participants | 0 Participants |
| Age, Customized 50-59 years of age | 8 Participants | 10 Participants | 2 Participants | 0 Participants | 0 Participants |
| Age, Customized ≥60 years of age | 8 Participants | 18 Participants | 2 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 43 Participants | 6 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 42 Participants | 6 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 12 Participants | 18 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 14 Participants | 26 Participants | 4 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 6 | 1 / 6 | 1 / 6 | 8 / 26 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 26 / 26 |
| serious Total, serious adverse events | 2 / 6 | 2 / 6 | 1 / 6 | 12 / 26 |
Outcome results
Primary
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.
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.
Population: All participants who enrolled prior to determination of the recommended phase II dose and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| CD24Fc 240 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| CD24Fc 480 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| CD24Fc 960 mg | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
Primary
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.
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.
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and completed the protocol's DLT evaluation period were analyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| CD24Fc 240 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| CD24Fc 480 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| CD24Fc 960 mg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
Primary
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.
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.
Population: All participants who enrolled prior to determination of the recommended phase II dose and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| CD24Fc 240 mg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| CD24Fc 480 mg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| CD24Fc 960 mg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
Primary
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.
Time frame: Up to 181 days
Population: Per protocol, only participants enrolled in the CD24Fc 960 mg arm (from both the dose escalation and expansion phases) who received at least one dose of study drug and underwent HCT were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Open Label Expansion Arm Only: Grade III-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) | 159.0 Days | Standard Deviation 46.86 |
Comparison: A hazard ratio was calculated based on a Cox proportional hazards regression model with treatment as a factor using the robust sandwich covariance estimator, comparing the CD24Fc 960 mg arm to a matched control group consisting of 92 participants from the Center for International Blood and Marrow Transplant Research (CIBMTR) observational databases of clinical information on HCT, whose mean grade III-IV AGFS in days was 135.8 with an SD of 64.66.p-value: 0.027495% CI: [0.01, 0.62]Log Rank
Secondary
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.
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.
Population: All participants who received at least one dose of study drug and underwent HCT were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) | 144.2 Days | Standard Deviation 74.98 |
| CD24Fc 240 mg | Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) | 145.7 Days | Standard Deviation 77.01 |
| CD24Fc 480 mg | Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) | 116.2 Days | Standard Deviation 86.69 |
| CD24Fc 960 mg | Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) | 125.4 Days | Standard Deviation 64.93 |
Comparison: A hazard ratio was calculated based on a Cox proportional hazards regression model with treatment as a factor using the robust sandwich covariance estimator, comparing the CD24Fc 960 mg arm to a matched control group consisting of 92 participants from the Center for International Blood and Marrow Transplant Research (CIBMTR) observational databases of clinical information on HCT, whose mean grade II-IV AGFS in days was 104.7 with an SD of 72.28.p-value: 0.098895% CI: [0.3, 1.08]Log Rank
Secondary
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
Time frame: Up to 380 days
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and underwent HCT were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | GVHD-Free and Relapse-Free Survival (GRFS) Following HCT | 178.7 Days | Standard Deviation 151.48 |
| CD24Fc 240 mg | GVHD-Free and Relapse-Free Survival (GRFS) Following HCT | 260.5 Days | Standard Deviation 99.54 |
| CD24Fc 480 mg | GVHD-Free and Relapse-Free Survival (GRFS) Following HCT | 250.3 Days | Standard Deviation 149.68 |
| CD24Fc 960 mg | GVHD-Free and Relapse-Free Survival (GRFS) Following HCT | 227.2 Days | Standard Deviation 123.63 |
Secondary
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.
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.
Population: All participants who received at least one dose of study drug and underwent HCT were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT) | 276.3 Days | Standard Deviation 132.25 |
| CD24Fc 240 mg | Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT) | 343.0 Days | Standard Deviation 64.34 |
| CD24Fc 480 mg | Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT) | 343.5 Days | Standard Deviation 72.45 |
| CD24Fc 960 mg | Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT) | 321.2 Days | Standard Deviation 97.62 |
Comparison: A hazard ratio was calculated based on a Cox proportional hazards regression model with treatment as a factor using the robust sandwich covariance estimator, comparing the CD24Fc 960 mg arm to a matched control group consisting of 92 participants from the Center for International Blood and Marrow Transplant Research (CIBMTR) observational databases of clinical information on HCT, whose mean OS in days was 319.3 with an SD of 93.83.p-value: 0.908895% CI: [0.43, 2.88]Log Rank
Secondary
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.
Time frame: Up to 380 days
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and underwent HCT were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Experiencing Chronic GVHD Following HCT | 33.3 Percentage of Participants |
| CD24Fc 240 mg | Percentage of Participants Experiencing Chronic GVHD Following HCT | 50.0 Percentage of Participants |
| CD24Fc 480 mg | Percentage of Participants Experiencing Chronic GVHD Following HCT | 50.0 Percentage of Participants |
| CD24Fc 960 mg | Percentage of Participants Experiencing Chronic GVHD Following HCT | 83.3 Percentage of Participants |
Secondary
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.
Time frame: Up to approximately 108 days
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and underwent HCT were analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT | 16.7 Percentage of Participants |
| CD24Fc 240 mg | Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT | 33.3 Percentage of Participants |
| CD24Fc 480 mg | Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT | 50.0 Percentage of Participants |
| CD24Fc 960 mg | Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT | 33.3 Percentage of Participants |
Secondary
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.
Time frame: Up to approximately 101 days
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and underwent HCT were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT) | 33.3 Percentage of Participants |
| CD24Fc 240 mg | Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT) | 83.3 Percentage of Participants |
| CD24Fc 480 mg | Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT) | 33.3 Percentage of Participants |
| CD24Fc 960 mg | Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT) | 100.0 Percentage of Participants |
Secondary
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.
Time frame: Up to 380 days
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and underwent HCT were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT | 16.7 Percentage of Participants |
| CD24Fc 240 mg | Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT | 16.7 Percentage of Participants |
| CD24Fc 480 mg | Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT | 0.0 Percentage of Participants |
| CD24Fc 960 mg | Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT | 0.0 Percentage of Participants |
Secondary
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.
Time frame: Up to 380 days
Population: All participants who enrolled prior to determination of the recommended phase II dose, received at least one dose of study drug, and underwent HCT were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Experiencing Relapse Following HCT | 33.3 Percentage of Participants |
| CD24Fc 240 mg | Percentage of Participants Experiencing Relapse Following HCT | 0.0 Percentage of Participants |
| CD24Fc 480 mg | Percentage of Participants Experiencing Relapse Following HCT | 16.7 Percentage of Participants |
| CD24Fc 960 mg | Percentage of Participants Experiencing Relapse Following HCT | 16.7 Percentage of Participants |
Secondary
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.
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
Population: All participants who received at least one dose of study drug and underwent HCT were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT) | 232.7 Days | Standard Deviation 152.48 |
| CD24Fc 240 mg | Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT) | 342.5 Days | Standard Deviation 64.11 |
| CD24Fc 480 mg | Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT) | 335.2 Days | Standard Deviation 92.82 |
| CD24Fc 960 mg | Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT) | 296.2 Days | Standard Deviation 119.06 |
Comparison: A hazard ratio was calculated based on a Cox proportional hazards regression model with treatment as a factor using the robust sandwich covariance estimator, comparing the CD24Fc 960 mg arm to a matched control group consisting of 92 participants from the Center for International Blood and Marrow Transplant Research (CIBMTR) observational databases of clinical information on HCT, whose mean RFS in days was 296.0 with an SD of 115.32.p-value: 0.613195% CI: [0.66, 2.46]Log Rank