Graft Failure
Conditions
Keywords
HSCT, allo-HSCT, Graft failure, emapalumab, interferon gamma, CXCL9
Brief summary
This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ in patients at risk of GF. Patients presenting CXCL9 levels above a defined threshold and other clinical criteria will be eligible to receive emapalumab. Both children and adults, with malignant and non-malignant underlying diseases, receiving allo-HSCT who are at high risk of GF as defined in the inclusion criteria will be included in the study. The main objective of the study is to determine the appropriate emapalumab dose regimen neutralizing interferon gamma (IFNγ) activity to pre-empt graft failure post allo-HSCT in a population with various underlying diseases and at high risk of graft failure (GF). Maximum 3 cohorts are foreseen to determine the appropriate dose regimen to pre-emptively treat patients at risk of primary GF. Emapalumab will be administered by IV infusion and treatment will last up to 56 days (15 infusions) or until evidence of engraftment. The study is expected to last approximately 3 years from screening to the last follow-up phone call for each patient.
Detailed description
This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ in patients at risk of GF. Patients presenting CXCL9 levels above a defined threshold and other clinical criteria will be eligible to receive emapalumab. Both children and adults, with malignant and non-malignant underlying diseases, receiving allo-HSCT who are at high risk of GF as defined in the inclusion criteria will be included in the study. The main objective of the study will be to determine the appropriate emapalumab dose regimen neutralizing interferon gamma (IFNγ) activity to pre-empt graft failure post allo-HSCT in a population with various underlying diseases and at high risk of graft failure (GF). Maximum 3 cohorts are foreseen to determine the appropriate dose regimen to pre-emptively treat patients at risk of primary GF. Emapalumab will be administered by IV infusion over 1 to 2 hours depending on the volume of the infusion. Treatment will last up to 56 days (15 infusions) or until evidence of engraftment. The study is comprised of the following study periods: screening (Day -21 to Day -8), allogeneic HSCT Day 0, monitoring period for primary GF (Day 1 up to Day 42), extended monitoring for secondary GF (up to Day 98), treatment period (up to 56 days) and follow-up period of 3 years after HSCT. The main objective of this proof of concept study is: • To determine the appropriate emapalumab dose regimen neutralizing interferon gamma (IFNγ) activity to pre-empt graft failure post allogeneic hematopoietic stem cell transplantation (HSCT) in a population with various underlying diseases and at high risk of graft failure (GF) The following objectives will support the dose selection: * To describe the Pharmacokinetic (PK) and Pharmacodynamic (PD) profiles of emapalumab post allogeneic HSCT (allo-HSCT) * To assess the efficacy of emapalumab to pre-empt GF post allo-HSCT * To assess the safety of emapalumab to pre-empt GF post allo-HSCT * To assess the immunogenicity of emapalumab post allo-HSCT Exploratory objectives will be: • To evaluate further data on the correlation between relevant biomarkers including C-X-C motif chemokine ligand 9 (CXCL9) levels and the risk of GF post allo-HSCT in a population with various underlying diseases and at high risk of GF also in the context of development of a diagnostic test. The study is expected to last approximately 3 years from screening to the last follow-up phone call for each patient.
Interventions
DRUGEmapalumab
Emapalumab is a fully human immunoglobulin G1 (IgG1) anti-IFNγ monoclonal antibody that binds to and neutralizes IFNγ. Emapalumab binds to both soluble and receptor (IFNγR1)-bound forms of IFNγ. Emapalumab is in development for treatment of primary and secondary HLH. The benefit expected from the targeted neutralization of IFNγ by emapalumab has been validated by the recent FDA approval of emapalumab for treatment of patients with pHLH who have refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. The safety profile has been assessed as acceptable. Emapalumab will be administered by intravenous infusion over 1 to 2 hours, depending on the volume of the infusion. The first infusion must be performed within 12 hours after CXCL9 levels have been measured above defined threshold. Treatment will last until maximum dose 15 (up to 56 days) or until evidence of engraftment, whichever comes first.
Sponsors
PRA Health Sciences
Cytel Inc.
Q2 Solutions
ABF Pharmaceutical Services GmbH
Cromsource
BioMérieux
Swedish Orphan Biovitrum
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Sequential dose cohorts. The first cohort of patients will receive a first emapalumab infusion of 6 mg/kg at TD0, followed by a second infusion at 3 mg/kg after 3 days. Subsequent infusions of 3 mg/kg will be every 3 or 4 days from previous dose until dose 15 or until engraftment. A maximum of 2 additional cohorts may be added to allow dosing regimen adaptation based on the PK/PD data observed from the previous cohort(s).
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Informed consent form signed by the patient (as required by law) or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable 2. Recipients of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and at high risk of graft failure (GF) based on at least one of the following criteria: * Receiving reduced intensity conditioning (RIC) or non-myeloablative conditioning (NMA) combined with a non-malignant disease or with a graft from Bone Marrow (BM) * Ex vivo T cell depleted graft * Graft from mismatched unrelated or haploidentical donor * Graft from Umbilical Cord Blood (UCB) 3. Patients requiring allo-HSCT with the following underlying diseases: * Malignant disease with high risk of GF, i.e. Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) with primary induction failure, second partial remission or relapse; Chronic Myeloid Leukemia (CML) in blastic phase (circulating blast or blast above 5% in biopsy); Non Hodgkin and Hodgkin Lymphoma and multiple myeloma with primary induction failure, second partial remission or relapse, myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) with splenomegaly, myelofibrosis with portal hypertension pre-transplant, MDS/MPD overlap syndromes * Non-malignant hematological diseases (e.g. autoimmune and metabolic disorders, aplastic anemia, Sickle cell anemia, Fanconi anemia, Diamond-Blackfan anemia, thalassemia, osteopetrosis, Wiskott-Aldrich syndrome, severe combined immunodeficiency, Hemophagocytic lymphohistiocytosis and other immunoregulatory disorders) 4. Male and female patients 5. Children aged at least 1 year and adults. Once the appropriate dose has been determined in one of the three cohorts and safety has been assessed by the Independent Data Monitoring Committee (IDMC), children less than 1 year old may be included in the study. 6. Females of child-bearing potential, defined as all women physiologically capable of becoming pregnant, require use of highly effective contraceptive measures from screening until 6 months after the last study drug administration
Exclusion criteria
1. Pregnant (or planning to become pregnant) or lactating female patients 2. Body weight \< 3 kg 3. Underlying malignant disease with Karnofsky/Lansky performance status equal or less than 40 or an Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 3 4. Patients presenting CXCL9 levels 10 times above the upper limit of the 95% interval (CI) of the normal range (reported in the CXCL9 assay laboratory manual) within 24 hours prior to HSCT 5. Clinically manifested infections caused by typical and atypical Mycobacteria, Salmonella, Histoplasma capsulatum and Herpes Zoster on the day of HSCT 6. Active or clinical suspicion of latent tuberculosis 7. Concomitant diseases that in the opinion of the Investigator may interfere with the assessment of emapalumab safety or efficacy 8. Receipt of a Bacille Calmette-Guerin (BCG) vaccine within 3 months prior to HSCT 9. Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to HSCT 10. Current or scheduled administration of therapies known to potentially trigger a cytokine release syndrome within 21 days from HSCT. 11. Patients having received IFNγ during the last 2 weeks prior to HSCT and/or who require treatment with IFNγ. 12. Patients having received emapalumab during the last 6 months prior to HSCT, unless it is known that emapalumab is no longer detectable. 13. Patients having received kinase inhibitors (Janus kinase inhibitors \[JAKi\] or bruton tyrosine kinase inhibitors \[BTKi\]) one week (or 5 half-lives whichever is greater) prior to HSCT. 14. Intolerance to antimicrobial and virus infection prophylaxis. 15. Hypersensitivity to emapalumab or any of the excipients. 16. Ongoing participation in an interventional trial or administration of any investigational drug (within 3 half-lives of the investigational drug) with the exception of interventional trials involving supportive care such as probiotics or antiemetics, graft manipulation, or use of new combinations or new dosing of conventional therapies for conditioning and prophylaxis pre-HSCT.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CXCL9 in Serum | From start of treatment to EoS Visit, up to 34 weeks | Serum concentration of C-X-C Motif Chemokine Ligand 9 (CXCL9) |
| Primary Graft Failure (GF) | From Hematopoietic stem-cell transplantation (HSCT) [Day 0] up to study termination, approximately 46 weeks | Number of participants with primary graft failure (GF) |
| Secondary GF | From HSCT (Day 0) up to study termination, approximately 46 weeks | Number of participants with secondary GF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ctrough (Emapalumab) | From start of treatment to EoS, up to 34 weeks | Concentration just before administration |
| Exploratory Biomarkers: Ferritin | From HSCT (Day 0) up to study termination, approximately 46 weeks | Ferritin - serum concentration |
| ADA and nAbs | From Start of treatment until EoS, up to 34 weeks | Number of participants developing antibodies against emapalumab (antidrug antibodies \[ADA\]) and Neutralizing antibodies (nAb) |
| Number of Participants With Mixed Donor Chimerism <10% and <20% | From HSCT (Day 0) up to study termination, approximately 46 weeks | Based on unselected leukocytes and based on sorted T cells |
| Number of Participants Receiving Thrombopoietic Agents, Stem Cell Boost, Donor Lymphocyte Infusion (DLI) | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Number of Participants Receiving a Second Allogeneic HSCT | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Number of Participants With Poor Graft Function | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Number of Participants With Event Free Engraftment | From HSCT (Day 0) up to study termination, approximately 46 weeks | defined as absence of GF or graft support |
| Number of Participants With Acute and/or Chronic Mild to Severe Graft Versus Host Disease (GvHD) | From HSCT (Day 0) up to study termination, approximately 46 weeks | (grade I to IV) |
| Biomarker Levels, in Particular IFNy and CXCL9, as Predictors of Primary and/or Secondary Graft Failure or Acute and/or Chronic GvHD | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Engraftment Syndrome | From HSCT (Day 0) up to study termination, approximately 46 weeks | Number of participants with engraftment syndrome |
| Number of Participants With Endothelial Complications | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Number of Participants With Relapse, Defined as Cumulative Incidence of Reoccurring Underlying Disease | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Survival Rate | From HSCT (Day 0) up to study termination, approximately 46 weeks | Number of patients alive at the end of study. |
| Change in Body Temperature | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in body temperature |
| Change in Heart Rate | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in heart rate |
| Change in Blood Pressure | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline systolic and diastolic blood pressure |
| Change in Body Weight | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in body weight |
| Change in Hematology: Red Blood Cells (RBC) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology: red blood cells (RBC) |
| Change in Hematology: Hematocrit | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology: hematocrit |
| Change in Hematology: Hemoglobin | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology: hemoglobin |
| Change in Hematology: Platelets | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology: platelets |
| Change in Hematology: White Blood Cells (WBC) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology: white blood cells (WBC) |
| Change in Hematology Differential: Lymphocytes | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology differential: lymphocytes |
| Change in Hematology Differential: Monocytes | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology differential: monocytes |
| Change in Hematology Differential: Neutrophils | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Hematology differential: neutrophils |
| Change in Biochemistry: Ferritin | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Ferritin |
| Change in Biochemistry: Glucose | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Glucose |
| Change in Biochemistry: C-reactive Protein | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: C-reactive protein |
| Change in Biochemistry: Sodium | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Sodium |
| Change in Biochemistry: Potassium | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Potassium |
| Change in Biochemistry: Chloride | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Chloride |
| Change in Biochemistry: Calcium | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Calcium |
| Change in Biochemistry: Magnesium | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Magnesium |
| Change in Biochemistry: Phosphate | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Phosphate |
| Change in Biochemistry: Aspartate Aminotransferase (AST) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Aspartate aminotransferase (AST) |
| Change in Biochemistry: Alanine Aminotransferase (ALT) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: alanine aminotransferase (ALT) |
| Change in Biochemistry: Gamma-glutamyl Transpeptidase (γGT) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: gamma-glutamyl transpeptidase (γGT) |
| Change in Biochemistry: Alkaline Phosphatase (ALP) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: alkaline phosphatase (ALP) |
| Change in Biochemistry: Lactate Dehydrogenase (LDH) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: lactate dehydrogenase (LDH) |
| Change in Biochemistry: Bilirubin | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: bilirubin (total, direct and indirect) |
| Change in Biochemistry: Triglycerides | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: triglycerides |
| Change in Biochemistry: Cholesterol | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: cholesterol (total and high-density lipoprotein \[HDL\]) |
| Change in Biochemistry: Creatinine | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Creatinine |
| Change in Biochemistry: Urea | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Urea |
| Activated Partial Thromboplastin (aPTT) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Coagulation: activated partial thromboplastin (aPTT) |
| Prothrombin Time (PT) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Coagulation: prothrombin time (PT) |
| Change in Urinalysis: Glucose | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: Glucose |
| Change in Urinalysis: Blood | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: Blood |
| Change in Urinalysis: Protein | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: Protein |
| Change in Urinalysis: Leucocytes | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: Leucocytes |
| Change in Urinalysis: Ketones | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: Ketones |
| Change in Biochemistry: Albumin | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Biochemistry: Albumin |
| Change in Urinalysis: Specific Gravity | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: specific gravity |
| Number of Subjects With Change in Donor Chimerism | From HSCT (Day 0) up to study termination, approximately 46 weeks | — |
| Change in HLA Antibodies | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in HLA antibodies against donor cells |
| Change From Baseline in Minimal Residual Disease (MRD) | From HSCT (Day 0) up to study termination, approximately 46 weeks | Only in patients presenting malignant disease |
| Change in Urinalysis: pH | From HSCT (Day 0) up to study termination, approximately 46 weeks | Change from baseline in Urinalysis: pH |
| Free & Total Interferon Gamma (IFNγ) in Serum | From start of treatment to EoS Visit, up to 34 weeks | Serum concentration of free and total Interferon gamma (IFNγ) |
| Emapalumab in Serum - Peak | From start of treatment to EoS, up to 34 weeks | Peak emapalumab serum concentration |
Countries
Australia, Canada, Israel
Participant flow
Recruitment details
One site was activated which screened a total of 3 subjects (2 enrolled; 1 screen failure). First and last subjects were enrolled 25May2021 and 07Oct2021 respectively.
Participants by arm
| Arm | Count |
|---|---|
| Emapalumab Treated Patients treated with emapalumab (i.e. patients who met the protocol requirements for initiating emapalumab treatment) | 0 |
| Non-emapalumab Treated Patients not treated with emapalumab (i.e.patients who did not meet the protocol requirements for initiating emapalumab treatment) | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up (3 Years From HSCT) | Early termination of study. | 0 | 2 |
Baseline characteristics
| Characteristic | Non-emapalumab Treated | Total |
|---|---|---|
| ABO incompatibility Major | 1 Participants | 1 Participants |
| ABO incompatibility No incompatibility | 1 Participants | 1 Participants |
| Age, Categorical <=18 years | 2 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Graft - Donor type Matched unrelated donor | 1 Participants | 1 Participants |
| Graft - Donor type Mismatched unrelated donor | 1 Participants | 1 Participants |
| Graft - Source of stem cells Bone marrow (BM) | 1 Participants | 1 Participants |
| Graft - Source of stem cells Peripheral blood stem cell (PBSC) | 1 Participants | 1 Participants |
| Graft - Type of conditioning Non myeloablative regimen (NMA) | 1 Participants | 1 Participants |
| Graft - Type of conditioning Reduced Intensity Conditioning (RIC) | 1 Participants | 1 Participants |
| Mean CXCL9 concentration (prior to HSCT) | 203.50 pg/mL | 203.5 pg/mL |
| Number of transplanted cells | 290.9 million cells | 290.9 million cells |
| Region of Enrollment Canada | 2 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
| Underlying disease: Aplastic anemia | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 2 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 2 |
Outcome results
Primary
CXCL9 in Serum
Serum concentration of C-X-C Motif Chemokine Ligand 9 (CXCL9)
Time frame: From start of treatment to EoS Visit, up to 34 weeks
Population: No efficacy data was collected since no subject received study treatment.
Primary
Primary Graft Failure (GF)
Number of participants with primary graft failure (GF)
Time frame: From Hematopoietic stem-cell transplantation (HSCT) [Day 0] up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Primary
Secondary GF
Number of participants with secondary GF
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Activated Partial Thromboplastin (aPTT)
Change from baseline in Coagulation: activated partial thromboplastin (aPTT)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
ADA and nAbs
Number of participants developing antibodies against emapalumab (antidrug antibodies \[ADA\]) and Neutralizing antibodies (nAb)
Time frame: From Start of treatment until EoS, up to 34 weeks
Population: No patients enrolled in the emapalumab arm.
Secondary
Biomarker Levels, in Particular IFNy and CXCL9, as Predictors of Primary and/or Secondary Graft Failure or Acute and/or Chronic GvHD
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change From Baseline in Minimal Residual Disease (MRD)
Only in patients presenting malignant disease
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Alanine Aminotransferase (ALT)
Change from baseline in Biochemistry: alanine aminotransferase (ALT)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Albumin
Change from baseline in Biochemistry: Albumin
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Alkaline Phosphatase (ALP)
Change from baseline in Biochemistry: alkaline phosphatase (ALP)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Aspartate Aminotransferase (AST)
Change from baseline in Biochemistry: Aspartate aminotransferase (AST)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Bilirubin
Change from baseline in Biochemistry: bilirubin (total, direct and indirect)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Calcium
Change from baseline in Biochemistry: Calcium
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Chloride
Change from baseline in Biochemistry: Chloride
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Cholesterol
Change from baseline in Biochemistry: cholesterol (total and high-density lipoprotein \[HDL\])
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: C-reactive Protein
Change from baseline in Biochemistry: C-reactive protein
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Creatinine
Change from baseline in Biochemistry: Creatinine
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Ferritin
Change from baseline in Biochemistry: Ferritin
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Gamma-glutamyl Transpeptidase (γGT)
Change from baseline in Biochemistry: gamma-glutamyl transpeptidase (γGT)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Glucose
Change from baseline in Biochemistry: Glucose
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Lactate Dehydrogenase (LDH)
Change from baseline in Biochemistry: lactate dehydrogenase (LDH)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Magnesium
Change from baseline in Biochemistry: Magnesium
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Phosphate
Change from baseline in Biochemistry: Phosphate
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Potassium
Change from baseline in Biochemistry: Potassium
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Sodium
Change from baseline in Biochemistry: Sodium
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Triglycerides
Change from baseline in Biochemistry: triglycerides
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Biochemistry: Urea
Change from baseline in Biochemistry: Urea
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Blood Pressure
Change from baseline systolic and diastolic blood pressure
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Body Temperature
Change from baseline in body temperature
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Body Weight
Change from baseline in body weight
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Heart Rate
Change from baseline in heart rate
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology Differential: Lymphocytes
Change from baseline in Hematology differential: lymphocytes
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology Differential: Monocytes
Change from baseline in Hematology differential: monocytes
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology Differential: Neutrophils
Change from baseline in Hematology differential: neutrophils
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology: Hematocrit
Change from baseline in Hematology: hematocrit
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology: Hemoglobin
Change from baseline in Hematology: hemoglobin
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology: Platelets
Change from baseline in Hematology: platelets
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology: Red Blood Cells (RBC)
Change from baseline in Hematology: red blood cells (RBC)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Hematology: White Blood Cells (WBC)
Change from baseline in Hematology: white blood cells (WBC)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in HLA Antibodies
Change from baseline in HLA antibodies against donor cells
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: Blood
Change from baseline in Urinalysis: Blood
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: Glucose
Change from baseline in Urinalysis: Glucose
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: Ketones
Change from baseline in Urinalysis: Ketones
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: Leucocytes
Change from baseline in Urinalysis: Leucocytes
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: pH
Change from baseline in Urinalysis: pH
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: Protein
Change from baseline in Urinalysis: Protein
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Change in Urinalysis: Specific Gravity
Change from baseline in Urinalysis: specific gravity
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Ctrough (Emapalumab)
Concentration just before administration
Time frame: From start of treatment to EoS, up to 34 weeks
Population: No patients enrolled in the emapalumab arm.
Secondary
Emapalumab in Serum - Peak
Peak emapalumab serum concentration
Time frame: From start of treatment to EoS, up to 34 weeks
Population: No patients enrolled in the emapalumab arm.
Secondary
Engraftment Syndrome
Number of participants with engraftment syndrome
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No patients enrolled in the emapalumab arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Emapalumab Treated | Engraftment Syndrome | 0 Participants |
| Non-emapalumab Treated | Engraftment Syndrome | 1 Participants |
Secondary
Exploratory Biomarkers: Ferritin
Ferritin - serum concentration
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Free & Total Interferon Gamma (IFNγ) in Serum
Serum concentration of free and total Interferon gamma (IFNγ)
Time frame: From start of treatment to EoS Visit, up to 34 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Number of Participants Receiving a Second Allogeneic HSCT
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Number of Participants Receiving Thrombopoietic Agents, Stem Cell Boost, Donor Lymphocyte Infusion (DLI)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Number of Participants With Acute and/or Chronic Mild to Severe Graft Versus Host Disease (GvHD)
(grade I to IV)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No patients enrolled in the emapalumab arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Emapalumab Treated | Number of Participants With Acute and/or Chronic Mild to Severe Graft Versus Host Disease (GvHD) | 0 Participants |
| Non-emapalumab Treated | Number of Participants With Acute and/or Chronic Mild to Severe Graft Versus Host Disease (GvHD) | 1 Participants |
Secondary
Number of Participants With Endothelial Complications
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Number of Participants With Event Free Engraftment
defined as absence of GF or graft support
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No patients enrolled in the emapalumab arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Emapalumab Treated | Number of Participants With Event Free Engraftment | 0 Participants |
| Non-emapalumab Treated | Number of Participants With Event Free Engraftment | 2 Participants |
Secondary
Number of Participants With Mixed Donor Chimerism <10% and <20%
Based on unselected leukocytes and based on sorted T cells
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No patients enrolled in the emapalumab arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Emapalumab Treated | Number of Participants With Mixed Donor Chimerism <10% and <20% | 0 Participants |
| Non-emapalumab Treated | Number of Participants With Mixed Donor Chimerism <10% and <20% | 0 Participants |
Secondary
Number of Participants With Poor Graft Function
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Number of Participants With Relapse, Defined as Cumulative Incidence of Reoccurring Underlying Disease
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Number of Subjects With Change in Donor Chimerism
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No patients enrolled in the emapalumab arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Emapalumab Treated | Number of Subjects With Change in Donor Chimerism | Change = 100% | 0 Participants |
| Emapalumab Treated | Number of Subjects With Change in Donor Chimerism | Change < 100% | 0 Participants |
| Non-emapalumab Treated | Number of Subjects With Change in Donor Chimerism | Change = 100% | 2 Participants |
| Non-emapalumab Treated | Number of Subjects With Change in Donor Chimerism | Change < 100% | 0 Participants |
Secondary
Prothrombin Time (PT)
Change from baseline in Coagulation: prothrombin time (PT)
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No efficacy data was collected since no subject received study treatment.
Secondary
Survival Rate
Number of patients alive at the end of study.
Time frame: From HSCT (Day 0) up to study termination, approximately 46 weeks
Population: No patients enrolled in the emapalumab arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-emapalumab Treated | Survival Rate | 2 Participants |