Phase II Trial of CD24Fc for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002)
Sponsor
OncoImmune, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02663622
Collaborator
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)
44
4
4
55.9
11
0.2
Study Details
Study Description
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 CD24Fc for acute GVHD prophylaxis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The first part of this study was a phase IIa randomized, double blind, placebo controlled, multi-center study to investigate adding CD24Fc 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 CD24Fc 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 CD24Fc : placebo randomization ratio was 3:1.
The second part was a prospective open label phase IIa expansion cohort trial investigating the addition of CD24Fc 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 CD24Fc 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
Study Type:
Interventional
Actual Enrollment
:
44 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of CD24Fc for Prevention of Acute Graft-versus-Host Disease Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplant
Actual Study Start Date
:
Sep 19, 2016
Actual Primary Completion Date
:
Jun 8, 2020
Actual Study Completion Date
:
May 18, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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) |
Drug: CD24Fc
Acute GVHD prophylaxis
Other Names:
Drug: Methotrexate
Acute GVHD prophylaxis
Other Names:
Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
|
| Experimental: 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) |
Drug: CD24Fc
Acute GVHD prophylaxis
Other Names:
Drug: Methotrexate
Acute GVHD prophylaxis
Other Names:
Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
|
| Experimental: 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) |
Drug: CD24Fc
Acute GVHD prophylaxis
Other Names:
Drug: Methotrexate
Acute GVHD prophylaxis
Other Names:
Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
|
| Placebo Comparator: 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) |
Drug: Methotrexate
Acute GVHD prophylaxis
Other Names:
Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
Drug: Placebo
100 ml saline IV infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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:
-
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.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Indiana University School of Medicine | Indianapolis | Indiana | United States | 46202 |
| 2 | The University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
| 3 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 4 | Ohio State University | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- OncoImmune, Inc.
- Ohio State University
- University of Michigan Rogel Cancer Center
- Indiana University School of Medicine
- Barbara Ann Karmanos Cancer Institute
- National Cancer Institute (NCI)
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
- 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. eCollection 2016. Review.
- 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). pii: 92293. doi: 10.1172/jci.insight.92293. eCollection 2017 Jul 20.
Responsible Party:
OncoImmune, Inc.
ClinicalTrials.gov Identifier:
NCT02663622
Other Study ID Numbers:
- 7110-002
- HUM00107805
- 15-4789
- R44CA221513
- R44CA246991
- UMCC 2015.181
- MK-7110-002
- NCI-2017-00017
- CD24Fc-002
First Posted:
Jan 26, 2016
Last Update Posted:
Jul 15, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Period Title: Overall Study | ||||
| STARTED | 6 | 6 | 6 | 26 |
| COMPLETED | 3 | 5 | 5 | 17 |
| NOT COMPLETED | 3 | 1 | 1 | 9 |
Baseline Characteristics
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 26 | 44 |
| Age, Customized (Count of Participants) | |||||
| 18-29 years of age |
0
0%
|
1
16.7%
|
2
33.3%
|
3
11.5%
|
6
13.6%
|
| 30-39 years of age |
1
16.7%
|
0
0%
|
0
0%
|
3
11.5%
|
4
9.1%
|
| 40-49 years of age |
1
16.7%
|
1
16.7%
|
0
0%
|
4
15.4%
|
6
13.6%
|
| 50-59 years of age |
2
33.3%
|
0
0%
|
0
0%
|
8
30.8%
|
10
22.7%
|
| ≥60 years of age |
2
33.3%
|
4
66.7%
|
4
66.7%
|
8
30.8%
|
18
40.9%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
2
33.3%
|
2
33.3%
|
12
46.2%
|
18
40.9%
|
| Male |
4
66.7%
|
4
66.7%
|
4
66.7%
|
14
53.8%
|
26
59.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
2.3%
|
| Not Hispanic or Latino |
6
100%
|
5
83.3%
|
6
100%
|
26
100%
|
43
97.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
1
3.8%
|
1
2.3%
|
| White |
6
100%
|
5
83.3%
|
6
100%
|
25
96.2%
|
42
95.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
2.3%
|
Outcome Measures
| Title | Number of Participants Who Experienced an Adverse Event (AE) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who enrolled prior to determination of the recommended phase II dose and received at least one dose of study drug. |
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
6
100%
|
6
100%
|
6
100%
|
6
23.1%
|
| Title | Number of Participants Who Discontinued Study Treatment Due to an AE |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who enrolled prior to determination of the recommended phase II dose and received at least one dose of study drug. |
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Open Label Expansion Arm Only: Grade III-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CD24Fc 960 mg |
|---|---|
| Arm/Group Description | 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) |
| Measure Participants | 26 |
| Mean (Standard Deviation) [Days] |
159.0
(46.86)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0274 |
| Comments | ||
| Method | Log Rank | |
| Comments | Log-rank test stratified by the matched sets | |
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% 0.01 to 0.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and underwent HCT were analyzed |
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 26 |
| Mean (Standard Deviation) [Days] |
144.2
(74.98)
|
145.7
(77.01)
|
116.2
(86.69)
|
125.4
(64.93)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CD24Fc 960 mg |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0988 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 0.57 | |
| Confidence Interval |
(2-Sided) 95% 0.30 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Number (95% Confidence Interval) [Percentage of Participants] |
16.7
278.3%
|
33.3
555%
|
50.0
833.3%
|
33.3
128.1%
|
| Title | Percentage of Participants Experiencing Chronic GVHD Following HCT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Number (95% Confidence Interval) [Percentage of Participants] |
33.3
555%
|
50.0
833.3%
|
50.0
833.3%
|
83.3
320.4%
|
| Title | Percentage of Participants Experiencing Relapse Following HCT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Number (95% Confidence Interval) [Percentage of Participants] |
33.3
555%
|
0.0
0%
|
16.7
278.3%
|
16.7
64.2%
|
| Title | Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Number (95% Confidence Interval) [Percentage of Participants] |
16.7
278.3%
|
16.7
278.3%
|
0.0
0%
|
0.0
0%
|
| Title | Percentage of Participants Experiencing Infection Following Hematopoietic Stem Cell Transplantation (HCT) |
|---|---|
| Description | The percentage of participants who experienced infection by approximately 101 days following HCT is presented. |
| Time Frame | Up to approximately 101 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Number [Percentage of Participants] |
33.3
555%
|
83.3
1388.3%
|
33.3
555%
|
100.0
384.6%
|
| Title | Overall Survival (OS) Following Hematopoietic Stem Cell Transplantation (HCT) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and underwent HCT were analyzed |
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 26 |
| Mean (Standard Deviation) [Days] |
276.3
(132.25)
|
343.0
(64.34)
|
343.5
(72.45)
|
321.2
(97.62)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CD24Fc 960 mg |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9088 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.12 | |
| Confidence Interval |
(2-Sided) 95% 0.43 to 2.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | GVHD-Free and Relapse-Free Survival (GRFS) Following HCT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Days] |
178.7
(151.48)
|
260.5
(99.54)
|
250.3
(149.68)
|
227.2
(123.63)
|
| Title | Relapse-Free Survival (RFS) Following Hematopoietic Stem Cell Transplantation (HCT) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and underwent HCT were analyzed |
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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) |
| Measure Participants | 6 | 6 | 6 | 26 |
| Mean (Standard Deviation) [Days] |
232.7
(152.48)
|
342.5
(64.11)
|
335.2
(92.82)
|
296.2
(119.06)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CD24Fc 960 mg |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6131 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 2.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 1134 days for All-Cause Mortality. Up to 1131 days for all adverse events. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg (Multi-dose) | ||||
| Arm/Group Description | 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) | 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) | 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) | 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) | ||||
All Cause Mortality |
||||||||
| Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg (Multi-dose) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 1/6 (16.7%) | 1/6 (16.7%) | 8/26 (30.8%) | ||||
Serious Adverse Events |
||||||||
| Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg (Multi-dose) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | 2/6 (33.3%) | 1/6 (16.7%) | 12/26 (46.2%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Nausea | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Stomatitis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Vomiting | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Hepatobiliary disorders | ||||||||
| Venoocclusive liver disease | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Immune system disorders | ||||||||
| Graft versus host disease in gastrointestinal tract | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Graft versus host disease in skin | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Infections and infestations | ||||||||
| Cytomegalovirus infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Cytomegalovirus viraemia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Device related infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Pneumonia | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Stenotrophomonas infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Thrombophlebitis septic | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Upper respiratory tract infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Urinary tract infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Subdural haematoma | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Investigations | ||||||||
| Platelet count decreased | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Weight decreased | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Dehydration | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthritis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Polymyalgia rheumatica | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Nervous system disorders | ||||||||
| Cognitive disorder | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Somnolence | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Pulmonary embolism | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Rash maculo-papular | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Stevens-Johnson syndrome | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | CD24Fc 240 mg | CD24Fc 480 mg | CD24Fc 960 mg (Multi-dose) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 26/26 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 4/6 (66.7%) | 15 | 6/6 (100%) | 29 | 5/6 (83.3%) | 18 | 22/26 (84.6%) | 89 |
| Febrile neutropenia | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 3/26 (11.5%) | 3 |
| Cardiac disorders | ||||||||
| Sinus tachycardia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Ear and labyrinth disorders | ||||||||
| Ear pain | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Hypoacusis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Eye disorders | ||||||||
| Eye irritation | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Lacrimation increased | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Retinal haemorrhage | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Vision blurred | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Abdominal pain | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 7/26 (26.9%) | 9 |
| Angina bullosa haemorrhagica | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Colitis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Constipation | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 3/26 (11.5%) | 3 |
| Diarrhoea | 4/6 (66.7%) | 7 | 2/6 (33.3%) | 2 | 4/6 (66.7%) | 6 | 18/26 (69.2%) | 23 |
| Dry mouth | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Dyspepsia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Dysphagia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Flatulence | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/26 (0%) | 0 |
| Haemorrhoids | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Nausea | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 3/6 (50%) | 5 | 9/26 (34.6%) | 9 |
| Oesophageal pain | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Oesophagitis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 2/26 (7.7%) | 2 |
| Oral pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/26 (0%) | 0 |
| Paraesthesia oral | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Proctalgia | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Stomatitis | 6/6 (100%) | 19 | 6/6 (100%) | 13 | 6/6 (100%) | 18 | 25/26 (96.2%) | 46 |
| Tongue oedema | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Vomiting | 3/6 (50%) | 4 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 9/26 (34.6%) | 11 |
| General disorders | ||||||||
| Catheter site bruise | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Catheter site oedema | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Catheter site swelling | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Chills | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Fatigue | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 10/26 (38.5%) | 11 |
| Oedema peripheral | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/26 (15.4%) | 4 |
| Pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Pyrexia | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 11/26 (42.3%) | 21 |
| Infections and infestations | ||||||||
| Clostridium difficile infection | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Conjunctivitis | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Cytomegalovirus infection | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 3 |
| Rash pustular | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Upper respiratory tract infection | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 3/6 (50%) | 4 | 3/6 (50%) | 6 | 1/6 (16.7%) | 1 | 13/26 (50%) | 31 |
| Aspartate aminotransferase increased | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 7 | 1/6 (16.7%) | 1 | 11/26 (42.3%) | 23 |
| Blood alkaline phosphatase increased | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 4/26 (15.4%) | 5 |
| Blood bilirubin increased | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/26 (15.4%) | 5 |
| Blood cholesterol increased | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Blood creatinine increased | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 7/26 (26.9%) | 8 |
| Electrocardiogram QT prolonged | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Lymphocyte count decreased | 3/6 (50%) | 18 | 6/6 (100%) | 27 | 5/6 (83.3%) | 15 | 4/26 (15.4%) | 10 |
| Neutrophil count decreased | 3/6 (50%) | 11 | 5/6 (83.3%) | 19 | 6/6 (100%) | 20 | 21/26 (80.8%) | 66 |
| Platelet count decreased | 5/6 (83.3%) | 21 | 6/6 (100%) | 38 | 6/6 (100%) | 32 | 22/26 (84.6%) | 132 |
| Weight decreased | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 3/26 (11.5%) | 3 |
| Weight increased | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| White blood cell count decreased | 4/6 (66.7%) | 21 | 6/6 (100%) | 23 | 6/6 (100%) | 23 | 16/26 (61.5%) | 75 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 8/26 (30.8%) | 12 |
| Fluid overload | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Hypercalcaemia | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/26 (0%) | 0 |
| Hyperglycaemia | 3/6 (50%) | 10 | 5/6 (83.3%) | 13 | 4/6 (66.7%) | 12 | 11/26 (42.3%) | 34 |
| Hyperkalaemia | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 2 | 3/6 (50%) | 5 | 3/26 (11.5%) | 3 |
| Hypermagnesaemia | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Hypernatraemia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 2/26 (7.7%) | 2 |
| Hypertriglyceridaemia | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 2/6 (33.3%) | 2 | 7/26 (26.9%) | 8 |
| Hypoalbuminaemia | 5/6 (83.3%) | 7 | 5/6 (83.3%) | 12 | 4/6 (66.7%) | 4 | 12/26 (46.2%) | 21 |
| Hypocalcaemia | 3/6 (50%) | 5 | 5/6 (83.3%) | 12 | 1/6 (16.7%) | 1 | 12/26 (46.2%) | 30 |
| Hypoglycaemia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Hypokalaemia | 2/6 (33.3%) | 7 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 8/26 (30.8%) | 15 |
| Hypomagnesaemia | 3/6 (50%) | 11 | 3/6 (50%) | 6 | 4/6 (66.7%) | 7 | 19/26 (73.1%) | 46 |
| Hyponatraemia | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 4 | 3/6 (50%) | 3 | 7/26 (26.9%) | 9 |
| Hypophosphataemia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/26 (15.4%) | 10 |
| Vitamin D deficiency | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Back pain | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Bone pain | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Muscular weakness | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Musculoskeletal chest pain | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Pain in extremity | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Nervous system disorders | ||||||||
| Aphasia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Burning sensation | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Depressed level of consciousness | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Dizziness | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 2/26 (7.7%) | 3 |
| Dysgeusia | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 3/26 (11.5%) | 3 |
| Headache | 4/6 (66.7%) | 4 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 7/26 (26.9%) | 13 |
| Paraesthesia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Tremor | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 4/26 (15.4%) | 4 |
| Psychiatric disorders | ||||||||
| Agitation | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Anxiety | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/26 (0%) | 0 |
| Confusional state | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Delirium | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Hallucination | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Insomnia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/26 (15.4%) | 4 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 4 |
| Cystitis noninfective | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 4 |
| Micturition urgency | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Pollakiuria | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Urinary retention | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Pelvic pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/26 (0%) | 0 |
| Pruritus genital | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Scrotal pain | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 5/26 (19.2%) | 6 |
| Dyspnoea | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/26 (15.4%) | 4 |
| Epistaxis | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 | 3/26 (11.5%) | 3 |
| Hypoxia | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 3 |
| Nasal congestion | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Oropharyngeal pain | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Pleural effusion | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Pneumomediastinum | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Rhinitis allergic | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Upper-airway cough syndrome | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Dermatitis acneiform | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/26 (0%) | 0 |
| Erythema | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Pruritus | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 7/26 (26.9%) | 7 |
| Rash maculo-papular | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Vascular disorders | ||||||||
| Hypertension | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 3/26 (11.5%) | 15 |
| Hypotension | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Orthostatic hypotension | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme LLC |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
OncoImmune, Inc.
ClinicalTrials.gov Identifier:
NCT02663622
Other Study ID Numbers:
- 7110-002
- HUM00107805
- 15-4789
- R44CA221513
- R44CA246991
- UMCC 2015.181
- MK-7110-002
- NCI-2017-00017
- CD24Fc-002
First Posted:
Jan 26, 2016
Last Update Posted:
Jul 15, 2022
Last Verified:
Jun 1, 2022