An Open-Label Study of Defibrotide for the Prevention of Acute Graft-versus-Host-Disease (AGvHD)

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03339297
• Collaborator: (none)
• Enrollment: 152
• Locations: 62
• Arms: 2
• Actual Duration (Months): 26.6
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a study comparing the defibrotide prophylaxis arm vs standard of care arm for the prevention of aGvHD.

Condition or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease; Acute-graft-versus-host Disease	Drug: Defibrotide; Drug: Standard of Care	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Prospective, Randomized, Open-Label Study on the Efficacy of Defibrotide Added to Standard of Care Immunoprophylaxis for the Prevention of Acute Graft-versus-Host-Disease in Adult and Pediatric Patients After Allogeneic Hematopoietic Stem Cell Transplant
• Actual Study Start Date: Feb 21, 2018
• Actual Primary Completion Date: May 12, 2020
• Actual Study Completion Date: May 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Defibrotide Prophylaxis Standard of Care Immunoprophylaxis + Defibrotide	Drug: Defibrotide; 6.25 mg/kg via 2-hour IV infusion every 6 hours; Drug: Standard of Care; Administered according to local institutional guidelines, physician preference, and patient need.
Active Comparator: Standard of Care Standard of Care Immunoprophylaxis Alone	Drug: Standard of Care; Administered according to local institutional guidelines, physician preference, and patient need.

Outcome Measures

Primary Outcome Measures

1. Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) [HSCT Day (Day +0 post-HSCT) through Day +100 post-HSCT]

   Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the International Bone Marrow Transplant Registry (IBMTR) Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.

Secondary Outcome Measures

1. Cumulative Incidence Percentage of Grade B to D aGvHD by Day +180 Post-HSCT [HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT]

   Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the IBMTR Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.

2. Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by Days +100 and +180 Post-HSCT [HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT]

   Grade B to D aGvHD was defined using the IBMTR Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.

3. Cumulative Incidence Percentage of Grade C to D aGvHD by Days +100 and +180 Post-HSCT [HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT]

   Cumulative Incidence Percentage of Grade C to D aGvHD was defined using the IBMTR Severity Index. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.

4. Cumulative Incidence Percentage of Disease Relapse by Days +100 and +180 Post-HSCT [HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT]

   Disease relapse was defined by either morphological evidence of acute leukemia or Myelodysplastic syndrome (MDS) consistent with pre-transplant features, documented or not by biopsy. The event was defined as an increase in size of prior sites of disease or evidence of new sites of disease, documented or not by biopsy. Disease relapse was diagnosed when there was morphological or clinical evidence of the following: reappearance of leukemia blast cells in the peripheral blood, or >5% blasts in the bone marrow (BM), not attributable to another cause (eg, BM regeneration), or the appearance of previous or new dysplastic changes (MDS specific) within the BM, with or without falling donor chimerism, or the development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid, or institution of therapy to treat relapsed disease, including donor lymphocyte infusion.

5. Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days Post-HSCT [HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT]

   For each treatment arm, the cumulative incidence rate of systemic steroid use for the treatment of aGvHD by Day +180 post-HSCT will be estimated using the cumulative incidence competing risk estimator. The calculation of the cumulative incidence rates and the stratified Gray's test was carried out using the LIFETEST procedure in SAS version 9.4. If the participant experienced a competing risk event, then the initiation date was used to calculate the time-to-event variable.

6. Change From Baseline to Days +100 and +180 Post-HSCT in the Physical Wellbeing Subscale as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score [Baseline through Days +100 and +180 post-HSCT]

   The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT physical wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.

7. Change From Baseline to Days +100 and +180 Post-HSCT in the Social/Family Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score [Baseline through Days +100 and +180 post-HSCT]

   The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT social/family wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.

8. Change From Baseline to Days +100 and +180 Post-HSCT in the Emotional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score [Baseline through Days +100 and +180 post-HSCT]

   The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT emotional wellbeing subscale scores range from a minimum of 0 to a maximum of 24, with higher scores indicating better quality of life.

9. Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score [Baseline through Days +100 and +180 post HSCT]

   The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT functional wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.

10. Change From Baseline to Days +100 and +180 Post-HSCT in the Bone Marrow Transplantation Subscale (BMTS) as Measured by the FACT-BMT Questionnaire Score [Baseline through Days +100 and +180 post-HSCT]

    The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT-BMT subscale scores range from a minimum of 0 to a maximum of 40, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.

11. Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score [Baseline through Days +100 and +180 post-HSCT]

    The FACT-General (FACT-G) is a core component of the FACT-BMT, and includes 4 of the 5 subscales included in the FACT-BMT total score (FACT physical wellbeing score, FACT social/family wellbeing score, FACT emotional wellbeing score, the FACT functional wellbeing score). In line with this similarity, results of the FACT-G exhibited the same pattern as described for the FACT-BMT total score. The FACT-G scores range from a minimParticipants were age ≥16 years at baseline.

12. Change From Baseline to Days +100 and +180 Post-HSCT in the FACT-BMT Total Score [Baseline through Days +100 and +180 post-HSCT]

    The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT-BMT total score range is from a minimum of 0 to a maximum of 148, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.

13. Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant-Trial Outcomes Index (FACT-BMT-TOI) [Baseline through Days +100 and +180 post-HSCT]

    The FACT-BMT-TOI is defined as the sum of the FACT physical wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. Scores range from a minimum of 0 to a maximum of 96, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.

14. Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes Measured Based on the EQ-5D-5L Index Value for Health States [Baseline through Days +100 and +180 post-HSCT]

    The 5-Level EuroQol-5D health questionnaire (EQ-5D-5L) index value, which is country-specific, was only performed for participants in the US. The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Change from the baseline assessment to Days +100 and +180 post-HSCT in the index value was assessed. The index value total range is from a minimum value of -1 to a maximum value of +1. A higher EQ-5D-5L index value represents better quality of life (QoL), thus a positive change in the index value represents improved QoL.

15. Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes as Measured Based on the EQ Visual Analog Scale (EQ VAS) [Baseline through Days +100 and +180 post-HSCT]

    The EQ VAS score at baseline and each of the post-HSCT assessments was summarized and presented using descriptive statistics. A higher EQ VAS score represents better QoL. For each of the post-HSCT assessments, change between baseline and that assessment in the EQ VAS score was calculated similarly to the EQ-5D-5L index value for a specific participant and was summarized and presented using descriptive statistics. The score ranges from a minimum of 0 and a maximum of 100. A negative change in the score indicates a decrease in quality of life.

16. Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years [Baseline through Day +100 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

17. Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years [Baseline through Day +180 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

18. Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years [Baseline through Day +100 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Days +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

19. Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years [Baseline through Day +180 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

20. Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years [Baseline through Day +100 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

21. Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years [Baseline through Day +180 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

22. Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years [Baseline through Day +100 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

23. Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years [Baseline through Day +180 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

24. Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years [Baseline through Day +100 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

25. Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years [Baseline through Day +180 post-HSCT]

    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participant must be ≥1 year of age at screening and undergoing allogeneic Hematopoietic Stem Cell Transplant (HSCT).

2. Participant must be diagnosed with acute leukemia in morphologic complete remission (CR1 or CR2) or with Myelodysplastic syndrome (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow

3. Participant must have planned to receive either a myeloablative or reduced-intensity conditioning regimen and have an unrelated donor who is human leukocyte antigen (HLA) matched or single-allele mismatched

4. Participant must receive the following medical regimen as part of standard of care immunoprophylaxis for GvHD in either study arm at doses and regimen determined by local institutional guidelines, physician preference, and participant need:

Methotrexate (MTX) or Mycophenolate mofetil (MMF) + calcineurin inhibitor (Cyclosporine A [CSA] or Tacrolimus [TAC]) +/- Anti-thymocyte globulin (ATG) (ATG use is limited to 30% of participants).

1. Graft must be a CD3+ T-cell replete peripheral blood stem cell (PBSC) graft or non-manipulated bone marrow (BM) graft.

2. Adult participants must be able to understand and sign a written informed consent. For pediatric participants, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria:

1. Participant has had a prior autologous or allogeneic HSCT.

2. Participant is using or plans to use an investigational agent for the prevention of GvHD.

3. Participant is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study.

4. Participant, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

5. Participant has a psychiatric illness that would prevent the participant or legal guardian or representative from giving informed consent and/or assent.

6. Participant has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study.

7. Participant is pregnant or lactating and does not agree to stop breastfeeding.

8. Any other condition that would cause a risk to the participant if he/she participated in the trial.

9. Participant has a known history of hypersensitivity to defibrotide or any of the excipients.

10. Participant had acute bleeding that is clinically significant within 24 hours before the start of study treatment, defined as either of the following:

• Hemorrhage requiring >15 cc/kg of packed red blood cells (eg, pediatric participant weighing 20 kg and requiring 300 cc packed red blood cells/24 hours, or an adult weighing >70 kg and requiring 3 units of packed red blood cells/24hours) to replace blood loss, or

• Bleeding from a site which, in the investigator's opinion, constituted a potential life-threatening source (eg, pulmonary hemorrhage or central nervous system bleeding), irrespective of amount of blood loss

1. Participant used any medication that increases the risk of bleeding within 24 hours before the start of study treatment, including, but not limited to, systemic heparin, low molecular weight heparin, heparin analogs, alteplase, streptokinase, urokinase, antithrombin III, oral anticoagulants including warfarin, and other agents that increase the risk of bleeding. Participants may have received heparin or other anticoagulants for routine central venous line management and intermittent dialysis or ultrafiltration. Fibrinolytic instillation for central venous line occlusion was also permitted. Note: Heparin used to keep catheters open was allowed (up to 100 U/kg/day).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC Norris Cancer Center	Los Angeles	California	United States	90033
2	Mattel Children's Hospital UCLA	Los Angeles	California	United States	90095
3	Stanford University	Palo Alto	California	United States	94304
4	University of California, San Francisco Medical Center	San Francisco	California	United States	94143
5	Mayo Clinic Jacksonville - PPDS	Jacksonville	Florida	United States	32224
6	Blood & Marrow Transplant Center	Orlando	Florida	United States	32804
7	Emory University Hospital	Atlanta	Georgia	United States	30322
8	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
9	University of Kansas Medical Center	Westwood	Kansas	United States	66205
10	James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
11	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
12	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
13	Montefiore Einstein Cancer Center	Bronx	New York	United States	10467
14	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514
15	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
16	MUSC-Hollings Cancer Center	Charleston	South Carolina	United States	29425
17	VA Puget Sound Health Care System	Seattle	Washington	United States	98108
18	West Virginia University Hospital	Morgantown	West Virginia	United States	26506
19	Universitätsklinikum Innsbruck	Innsbruck		Austria	6020
20	Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH	Linz		Austria	4020
21	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
22	UZ Gent	Gent		Belgium	9000
23	UZ Leuven	Leuven		Belgium	3000
24	Specialized Hospital for Active Treatment of Haematological Diseases - Sofia	Sofia		Bulgaria	1756
25	Hôpital Maisonneuve-Rosemont	Montreal		Canada	H1T 2M4
26	Sainte Justine Hospital	Montreal		Canada	H3T 1C5
27	McGill University Health Center	Montreal		Canada	H4A 3J1
28	Klinichki Bolnicki Centar Zagreb	Zagreb		Croatia	10000
29	Hospital d Instructions des Armees Percy	Clamart		France	92141
30	CHRU Lille	Lille		France	59037
31	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse		France	31059
32	Institut Gustave Roussy	Villejuif		France	94805
33	Helios Klinikum Berlin Buch	Berlin		Germany	13125
34	Medizinische Universitätsklinik Knappschaftskrankenhaus	Bochum		Germany	44892
35	Klinikum Frankfurt (Oder) GmbH	Brandenburg		Germany	15236
36	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresden		Germany	01307
37	University Medicine Göttingen Germany	Göttingen		Germany	37075
38	Universitaetsklinikum Halle (Saale)	Halle		Germany	06120
39	Uniklinik Köln	Köln		Germany	50937
40	Universitatsklinikum Leipzig	Leipzig		Germany	04103
41	Klinikum Mannheim Universitätsklinikum gGmbH	Mannheim		Germany	68167
42	Klinikum rechts der Isar der Technischen Universität München	Munchen		Germany	81675
43	Klinikum der Universitat Regensburg	Regensburg		Germany	93053
44	Attikon University General Hospital	Athens		Greece	12462
45	University General Hospital of Patras	Patras		Greece	26500
46	ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda	Milano		Italy	20162
47	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	41236
48	Ospedale Pediatrico Bambino Gesù	Roma		Italy	00165
49	Centrum Onkologii im. Marii Sklodowskiej-Curie	Warsaw		Poland	00-001
50	Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku	Wrocław		Poland	53-439
51	Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.	Lisboa		Portugal	1099
52	Hospital Universitario Marques de Valdecilla	Coruña		Spain	15006
53	Hospital de Gran Canaria Doctor Negrin	Las Palmas De Gran Canaria		Spain	35010
54	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid		Spain	28222
55	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca		Spain	37007
56	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
57	Hospital Clinico Universitario de Valencia	Valencia		Spain	41013
58	Birmingham Heartlands Hospital	Birmingham		United Kingdom	B9 5SS
59	St James University Hospital	Leeds		United Kingdom	LS9 7TF
60	St. James University Hospital	Leeds		United Kingdom	LS9 7TF
61	Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW
62	Manchester Royal Infirmary	Manchester		United Kingdom	LE1 5WW

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 19, 2018
• Statistical Analysis Plan - Sep 22, 2020

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03339297
• Other Study ID Numbers: JZP963-201
• First Posted: Nov 13, 2017
• Last Update Posted: Aug 18, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Graft vs Host Disease; Defibrotide

Study Results

Participant Flow

Pre-assignment Detail	Informed Consent and/or assent was obtained from participants, parents/legal guardians or representatives.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Period Title: Overall Study
STARTED	79	73
COMPLETED	56	59
NOT COMPLETED	23	14

Baseline Characteristics

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis	Total
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.	Total of all reporting groups
Overall Participants	79	73	152
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.54 (16.952)	51.09 (16.621)	50.80 (16.741)
Sex: Female, Male (Count of Participants)
Female	38 48.1%	37 50.7%	75 49.3%
Male	41 51.9%	36 49.3%	77 50.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.3%	1 1.4%	2 1.3%
Not Hispanic or Latino	67 84.8%	63 86.3%	130 85.5%
Unknown or Not Reported	11 13.9%	9 12.3%	20 13.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.3%	4 5.5%	5 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 1.4%	1 0.7%
White	66 83.5%	63 86.3%	129 84.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	12 15.2%	5 6.8%	17 11.2%

Outcome Measures

1. Primary Outcome

Title	Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT)
Description	Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the International Bone Marrow Transplant Registry (IBMTR) Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Time Frame	HSCT Day (Day +0 post-HSCT) through Day +100 post-HSCT

Outcome Measure Data

Analysis Population Description

Cumulative Incidence Rate of Grade B to D Acute Graft Versus Host Disease (aGvHD) was assessed using the Intent-to-Treat Analysis Set.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	79	73
Number [cumulative incidence percentage]	38.4	47.1

2. Secondary Outcome

Title	Cumulative Incidence Percentage of Grade B to D aGvHD by Day +180 Post-HSCT
Description	Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the IBMTR Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Time Frame	HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Cumulative Incidence Rate of Grade B to D Acute Graft Versus Host Disease (aGvHD) was assessed using the Intent-to-Treat Analysis Set.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	79	73
Number [cumulative incidence percentage]	50.6	51.6

3. Secondary Outcome

Title	Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by Days +100 and +180 Post-HSCT
Description	Grade B to D aGvHD was defined using the IBMTR Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Time Frame	HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival was assessed using the Intent-to-Treat Analysis Set.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	79	73
Day +100 post-HSCT	60.3 76.3%	51.4 70.4%
Day +180 post-HSCT	45.1 57.1%	42.6 58.4%

4. Secondary Outcome

Title	Cumulative Incidence Percentage of Grade C to D aGvHD by Days +100 and +180 Post-HSCT
Description	Cumulative Incidence Percentage of Grade C to D aGvHD was defined using the IBMTR Severity Index. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Time Frame	HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Cumulative Incidence Rate of Grade C to D Acute Graft Versus Host Disease (aGvHD) was assessed using the Intent-to-Treat Analysis Set.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	79	73
Day +100 post-HSCT	16.5	21.5
Day +180 post-HSCT	22.7	25.9

5. Secondary Outcome

Title	Cumulative Incidence Percentage of Disease Relapse by Days +100 and +180 Post-HSCT
Description	Disease relapse was defined by either morphological evidence of acute leukemia or Myelodysplastic syndrome (MDS) consistent with pre-transplant features, documented or not by biopsy. The event was defined as an increase in size of prior sites of disease or evidence of new sites of disease, documented or not by biopsy. Disease relapse was diagnosed when there was morphological or clinical evidence of the following: reappearance of leukemia blast cells in the peripheral blood, or >5% blasts in the bone marrow (BM), not attributable to another cause (eg, BM regeneration), or the appearance of previous or new dysplastic changes (MDS specific) within the BM, with or without falling donor chimerism, or the development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid, or institution of therapy to treat relapsed disease, including donor lymphocyte infusion.
Time Frame	HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Cumulative Incidence Rate of Disease Relapse was assessed using the Intent-to-Treat Analysis Set.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	79	73
Day +100 post-HSCT	11.0	4.3
Day +180 post-HSCT	16.8	5.8

6. Secondary Outcome

Title	Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days Post-HSCT
Description	For each treatment arm, the cumulative incidence rate of systemic steroid use for the treatment of aGvHD by Day +180 post-HSCT will be estimated using the cumulative incidence competing risk estimator. The calculation of the cumulative incidence rates and the stratified Gray's test was carried out using the LIFETEST procedure in SAS version 9.4. If the participant experienced a competing risk event, then the initiation date was used to calculate the time-to-event variable.
Time Frame	HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Cumulative Incidence Rate of Systemic Steroids for the Treatment of aGvHD was assessed using the Intent-to-Treat Analysis Set.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	79	73
Number [cumulative incidence percentage]	38.2	28.6

7. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the Physical Wellbeing Subscale as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT physical wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprohylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-1.25 (5.069)	-1.41 (6.371)
Change from Baseline to Day +180 post-HSCT	-1.55 (5.230)	-1.54 (5.717)

8. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the Social/Family Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT social/family wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-0.56 (3.488)	-0.29 (5.716)
Change from Baseline to Day +180 post-HSCT	-0.78 (4.085)	-1.34 (3.380)

9. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the Emotional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT emotional wellbeing subscale scores range from a minimum of 0 to a maximum of 24, with higher scores indicating better quality of life.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	1.47 (4.910)	1.47 (3.659)
Change from Baseline to Day +180 post-HSCT	0.79 (4.683)	1.53 (3.458)

10. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT functional wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Time Frame	Baseline through Days +100 and +180 post HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-1.71 (5.622)	-2.11 (5.962)
Change from Baseline to Day +180 post-HSCT	-2.21 (7.241)	-0.95 (6.627)

11. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the Bone Marrow Transplantation Subscale (BMTS) as Measured by the FACT-BMT Questionnaire Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT-BMT subscale scores range from a minimum of 0 to a maximum of 40, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-0.88 (5.484)	-2.14 (5.900)
Change from Baseline to Day +180 post-HSCT	-2.33 (7.037)	-1.01 (6.173)

12. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score
Description	The FACT-General (FACT-G) is a core component of the FACT-BMT, and includes 4 of the 5 subscales included in the FACT-BMT total score (FACT physical wellbeing score, FACT social/family wellbeing score, FACT emotional wellbeing score, the FACT functional wellbeing score). In line with this similarity, results of the FACT-G exhibited the same pattern as described for the FACT-BMT total score. The FACT-G scores range from a minimParticipants were age ≥16 years at baseline.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone in a 1:1 ratio according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-2.38 (12.623)	-1.74 (15.623)
Change from Baseline to Day +180 post-HSCT	-4.03 (15.366)	-1.33 (13.613)

13. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the FACT-BMT Total Score
Description	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT-BMT total score range is from a minimum of 0 to a maximum of 148, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-3.24 (16.036)	-3.70 (19.854)
Change from Baseline to Day +180 post-HSCT	-6.38 (21.358)	-2.83 (18.079)

14. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant-Trial Outcomes Index (FACT-BMT-TOI)
Description	The FACT-BMT-TOI is defined as the sum of the FACT physical wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. Scores range from a minimum of 0 to a maximum of 96, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	-3.88 (13.110)	-5.24 (15.575)
Change from Baseline to Day +180 post-HSCT	-6.99 (17.393)	-3.33 (14.922)

15. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes Measured Based on the EQ-5D-5L Index Value for Health States
Description	The 5-Level EuroQol-5D health questionnaire (EQ-5D-5L) index value, which is country-specific, was only performed for participants in the US. The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Change from the baseline assessment to Days +100 and +180 post-HSCT in the index value was assessed. The index value total range is from a minimum value of -1 to a maximum value of +1. A higher EQ-5D-5L index value represents better quality of life (QoL), thus a positive change in the index value represents improved QoL.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	0.02 (0.092)	-0.01 (0.101)
Change from Baseline to Day +180 post-HSCT	0.02 (0.078)	-0.01 (0.121)

16. Secondary Outcome

Title	Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes as Measured Based on the EQ Visual Analog Scale (EQ VAS)
Description	The EQ VAS score at baseline and each of the post-HSCT assessments was summarized and presented using descriptive statistics. A higher EQ VAS score represents better QoL. For each of the post-HSCT assessments, change between baseline and that assessment in the EQ VAS score was calculated similarly to the EQ-5D-5L index value for a specific participant and was summarized and presented using descriptive statistics. The score ranges from a minimum of 0 and a maximum of 100. A negative change in the score indicates a decrease in quality of life.
Time Frame	Baseline through Days +100 and +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set were used in this analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	70	67
Change from Baseline to Day +100 post-HSCT	6.03 (20.599)	2.70 (15.004)
Change from Baseline to Day +180 post-HSCT	2.24 (29.023)	-0.90 (21.530)

17. Secondary Outcome

Title	Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +100 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	61	62
Condition improved	3 3.8%	4 5.5%
Condition unchanged	31 39.2%	28 38.4%
Condition deteriorated	8 10.1%	15 20.5%
Unknown	19 24.1%	15 20.5%

18. Secondary Outcome

Title	Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	57	61
Condition improved	3 3.8%	3 4.1%
Condition unchanged	26 32.9%	25 34.2%
Condition deteriorated	11 13.9%	14 19.2%
Unknown	17 21.5%	19 26%

19. Secondary Outcome

Title	Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Days +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +100 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	61	62
Condition improved	10 12.7%	9 12.3%
Condition unchanged	18 22.8%	20 27.4%
Condition deteriorated	14 17.7%	18 24.7%
Unknown	19 24.1%	15 20.5%

20. Secondary Outcome

Title	Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	57	61
Condition improved	6 7.6%	8 11%
Condition unchanged	23 29.1%	20 27.4%
Condition deteriorated	11 13.9%	14 19.2%
Unknown	17 21.5%	19 26%

21. Secondary Outcome

Title	Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +100 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	61	62
Condition improved	1 1.3%	0 0%
Condition unchanged	34 43%	37 50.7%
Condition deteriorated	7 8.9%	10 13.7%
Unknown	19 24.1%	15 20.5%

22. Secondary Outcome

Title	Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	57	61
Condition improved	2 2.5%	1 1.4%
Condition unchanged	34 43%	31 42.5%
Condition deteriorated	4 5.1%	10 13.7%
Unknown	17 21.5%	19 26%

23. Secondary Outcome

Title	Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +100 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	61	62
Condition improved	8 10.1%	7 9.6%
Condition unchanged	21 26.6%	22 30.1%
Condition deteriorated	13 16.5%	18 24.7%
Unknown	19 24.1%	15 20.5%

24. Secondary Outcome

Title	Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	57	61
Condition improved	10 12.7%	5 6.8%
Condition unchanged	16 20.3%	19 26%
Condition deteriorated	14 17.7%	18 24.7%
Unknown	17 21.5%	19 26%

25. Secondary Outcome

Title	Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +100 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	61	62
Condition improved	7 8.9%	10 13.7%
Condition unchanged	27 34.2%	30 41.1%
Condition deteriorated	8 10.1%	7 9.6%
Unknown	19 24.1%	15 20.5%

26. Secondary Outcome

Title	Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years
Description	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Time Frame	Baseline through Day +180 post-HSCT

Outcome Measure Data

Analysis Population Description

Only participants with age >=16 years at baseline in the Safety Analysis Set who were on the study at the time of the scheduled post-baseline assessment were included in the analysis.

Arm/Group Title	Defibrotide Prophylaxis	Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.	Participants were administered Standard of Care immunoprophylaxis alone according to local institutional guidelines, physician preference, and patient need.
Measure Participants	57	61
Condition improved	8 10.1%	12 16.4%
Condition unchanged	21 26.6%	23 31.5%
Condition deteriorated	11 13.9%	6 8.2%
Unknown	17 21.5%	20 27.4%

Adverse Events

Time Frame	All Adverse Events (AEs) and Serious Adverse Events (SAEs) were reported from the time of signed informed consent form (ICF) and were recorded up to Day +63 post-HSCT. SAEs considered by the investigator to be related to study drug or study procedures were reported up to Day +180 post-HSCT.
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs) were defined as events that occurred after randomization into this study. A TEAE is defined as any event with a start date on or after baseline through the end of the study, or any ongoing event that worsens in severity after baseline through the end of the study. Adverse events were assessed using the Safety Analysis Set.
Arm/Group Title	Defibrotide Prophylaxis		Standard of Care Immunoprophylaxis
Arm/Group Description	Participants were administered Defibrotide Prophylaxis solution intravenously by study personnel at a dose of 25 mg/kg/day (6.25 mg/kg via 2-hour IV infusion every 6 hours) and Standard of Care immunoprophylaxis according to local institutional guidelines, physician preference, and patient need.		Participants were administered Standard of Care immunoprophylaxis alone in a 1:1 ratio according to local institutional guidelines, physician preference, and patient need.
All Cause Mortality
	Defibrotide Prophylaxis		Standard of Care Immunoprophylaxis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/74 (13.5%)		9/70 (12.9%)
Serious Adverse Events
	Defibrotide Prophylaxis		Standard of Care Immunoprophylaxis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/74 (41.9%)		31/70 (44.3%)
Blood and lymphatic system disorders
Eosinophilia	1/74 (1.4%)		0/70 (0%)
Evans syndrome	1/74 (1.4%)		0/70 (0%)
Febrile neutropenia	1/74 (1.4%)		0/70 (0%)
Thrombotic microangiopathy	1/74 (1.4%)		0/70 (0%)
Cardiac disorders
Atrial flutter	1/74 (1.4%)		0/70 (0%)
Cardiac tamponade	0/74 (0%)		1/70 (1.4%)
Cardio-respiratory arrest	1/74 (1.4%)		0/70 (0%)
Cardiogenic shock	1/74 (1.4%)		1/70 (1.4%)
Sinus tachycardia	1/74 (1.4%)		0/70 (0%)
Stress cardiomyopathy	0/74 (0%)		1/70 (1.4%)
Supraventricular tachycardia	1/74 (1.4%)		0/70 (0%)
Gastrointestinal disorders
Abdominal pain	1/74 (1.4%)		0/70 (0%)
Acute abdomen	0/74 (0%)		1/70 (1.4%)
Diarrhoea	3/74 (4.1%)		2/70 (2.9%)
Intestinal haemorrhage	0/74 (0%)		1/70 (1.4%)
Nausea	2/74 (2.7%)		1/70 (1.4%)
Oesophagitis	1/74 (1.4%)		0/70 (0%)
Stomatitis	0/74 (0%)		1/70 (1.4%)
Upper gastrointestinal haemorrhage	1/74 (1.4%)		0/70 (0%)
Vomiting	2/74 (2.7%)		1/70 (1.4%)
General disorders
General physical health deterioration	0/74 (0%)		1/70 (1.4%)
Mucosal haemorrhage	1/74 (1.4%)		0/70 (0%)
Mucosal inflammation	1/74 (1.4%)		0/70 (0%)
Multiple organ dysfunction syndrome	1/74 (1.4%)		1/70 (1.4%)
Pyrexia	1/74 (1.4%)		0/70 (0%)
Transfusion reaction	0/74 (0%)		1/70 (1.4%)
Hepatobiliary disorders
Venoocclusive liver disease	0/74 (0%)		2/70 (2.9%)
Immune system disorders
Acute graft versus host disease	4/74 (5.4%)		1/70 (1.4%)
Acute graft versus host disease in skin	1/74 (1.4%)		4/70 (5.7%)
Graft versus host disease	0/74 (0%)		1/70 (1.4%)
Graft versus host disease in liver	0/74 (0%)		1/70 (1.4%)
Acute graft versus host disease in intestine	2/74 (2.7%)		1/70 (1.4%)
Infections and infestations
Arthritis bacterial	1/74 (1.4%)		0/70 (0%)
Bacterial sepsis	1/74 (1.4%)		0/70 (0%)
Bronchitis	0/74 (0%)		1/70 (1.4%)
Clostridium difficile colitis	1/74 (1.4%)		0/70 (0%)
Cystitis viral	1/74 (1.4%)		0/70 (0%)
Cytomegalovirus infection	0/74 (0%)		1/70 (1.4%)
Cytomegalovirus viraemia	0/74 (0%)		1/70 (1.4%)
Device related infection	1/74 (1.4%)		0/70 (0%)
Epstein-Barr viraemia	1/74 (1.4%)		0/70 (0%)
Epstein-Barr virus infection	1/74 (1.4%)		0/70 (0%)
Fungaemia	0/74 (0%)		1/70 (1.4%)
Respiratory tract infection	0/74 (0%)		1/70 (1.4%)
Sepsis	0/74 (0%)		2/70 (2.9%)
Septic shock	0/74 (0%)		2/70 (2.9%)
Serratia infection	0/74 (0%)		1/70 (1.4%)
Staphylococcal bacteraemia	0/74 (0%)		1/70 (1.4%)
Urinary tract infection	0/74 (0%)		1/70 (1.4%)
Urinary tract infection bacterial	0/74 (0%)		1/70 (1.4%)
Vascular device infection	0/74 (0%)		1/70 (1.4%)
Injury, poisoning and procedural complications
Toxicity to various agents	0/74 (0%)		1/70 (1.4%)
Investigations
Blood potassium decreased	0/74 (0%)		1/70 (1.4%)
Ejection fraction decreased	0/74 (0%)		1/70 (1.4%)
Metabolism and nutrition disorders
Decreased appetite	2/74 (2.7%)		1/70 (1.4%)
Dehydration	0/74 (0%)		1/70 (1.4%)
Failure to thrive	1/74 (1.4%)		0/70 (0%)
Hyperkalaemia	1/74 (1.4%)		0/70 (0%)
Hypokalaemia	0/74 (0%)		1/70 (1.4%)
Hypovolaemia	1/74 (1.4%)		0/70 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia	0/74 (0%)		1/70 (1.4%)
Acute myeloid leukaemia recurrent	0/74 (0%)		1/70 (1.4%)
Epstein-Barr virus associated lymphoproliferative disorder	0/74 (0%)		1/70 (1.4%)
Nervous system disorders
Cognitive disorder	1/74 (1.4%)		0/70 (0%)
Hypertensive encephalopathy	0/74 (0%)		1/70 (1.4%)
Syncope	1/74 (1.4%)		0/70 (0%)
Renal and urinary disorders
Acute kidney injury	3/74 (4.1%)		2/70 (2.9%)
Cystitis haemorrhagic	1/74 (1.4%)		1/70 (1.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/74 (1.4%)		1/70 (1.4%)
Dyspnoea	3/74 (4.1%)		0/70 (0%)
Epistaxis	1/74 (1.4%)		0/70 (0%)
Lung disorder	0/74 (0%)		1/70 (1.4%)
Pharyngeal inflammation	0/74 (0%)		1/70 (1.4%)
Pleural effusion	0/74 (0%)		1/70 (1.4%)
Pulmonary embolism	0/74 (0%)		1/70 (1.4%)
Pulmonary oedema	0/74 (0%)		1/70 (1.4%)
Respiratory failure	1/74 (1.4%)		1/70 (1.4%)
Skin and subcutaneous tissue disorders
Rash vesicular	1/74 (1.4%)		0/70 (0%)
Toxic skin eruption	1/74 (1.4%)		0/70 (0%)
Vascular disorders
Obstructive shock	0/74 (0%)		1/70 (1.4%)
Shock	0/74 (0%)		1/70 (1.4%)
Venoocclusive disease	1/74 (1.4%)		1/70 (1.4%)
Other (Not Including Serious) Adverse Events
	Defibrotide Prophylaxis		Standard of Care Immunoprophylaxis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/74 (100%)		70/70 (100%)
Blood and lymphatic system disorders
Anaemia	27/74 (36.5%)		30/70 (42.9%)
Febrile neutropenia	30/74 (40.5%)		20/70 (28.6%)
Leukopenia	9/74 (12.2%)		6/70 (8.6%)
Neutropenia	12/74 (16.2%)		17/70 (24.3%)
Thrombocytopenia	19/74 (25.7%)		19/70 (27.1%)
Cardiac disorders
Sinus tachycardia	9/74 (12.2%)		8/70 (11.4%)
Eye disorders
Dry eye	15/74 (20.3%)		6/70 (8.6%)
Eye swelling	0/74 (0%)		4/70 (5.7%)
Gastrointestinal disorders
Abdominal distension	8/74 (10.8%)		5/70 (7.1%)
Abdominal pain	13/74 (17.6%)		22/70 (31.4%)
Abdominal pain lower	4/74 (5.4%)		0/70 (0%)
Abdominal pain upper	5/74 (6.8%)		9/70 (12.9%)
Constipation	28/74 (37.8%)		29/70 (41.4%)
Diarrhoea	47/74 (63.5%)		53/70 (75.7%)
Dry mouth	7/74 (9.5%)		6/70 (8.6%)
Dyspepsia	4/74 (5.4%)		11/70 (15.7%)
Dysphagia	5/74 (6.8%)		3/70 (4.3%)
Flatulence	4/74 (5.4%)		3/70 (4.3%)
Haemorrhoids	6/74 (8.1%)		6/70 (8.6%)
Mouth ulceration	4/74 (5.4%)		1/70 (1.4%)
Nausea	56/74 (75.7%)		49/70 (70%)
Odynophagia	7/74 (9.5%)		3/70 (4.3%)
Oesophagitis	5/74 (6.8%)		0/70 (0%)
Stomatitis	42/74 (56.8%)		36/70 (51.4%)
Vomiting	39/74 (52.7%)		38/70 (54.3%)
General disorders
Asthenia	9/74 (12.2%)		6/70 (8.6%)
Catheter site pain	8/74 (10.8%)		9/70 (12.9%)
Chills	7/74 (9.5%)		6/70 (8.6%)
Fatigue	25/74 (33.8%)		25/70 (35.7%)
Mucosal inflammation	10/74 (13.5%)		17/70 (24.3%)
Oedema peripheral	19/74 (25.7%)		21/70 (30%)
Pain	5/74 (6.8%)		6/70 (8.6%)
Pyrexia	28/74 (37.8%)		24/70 (34.3%)
Immune system disorders
Graft versus host disease in skin	4/74 (5.4%)		2/70 (2.9%)
Infections and infestations
Clostridium difficile colitis	3/74 (4.1%)		4/70 (5.7%)
Cytomegalovirus infection	11/74 (14.9%)		14/70 (20%)
Oral candidiasis	0/74 (0%)		6/70 (8.6%)
Urinary tract infection	3/74 (4.1%)		6/70 (8.6%)
Injury, poisoning and procedural complications
Fall	5/74 (6.8%)		2/70 (2.9%)
Infusion related reaction	4/74 (5.4%)		6/70 (8.6%)
Limb injury	4/74 (5.4%)		1/70 (1.4%)
Skin abrasion	1/74 (1.4%)		4/70 (5.7%)
Investigations
Alanine aminotransferase increased	3/74 (4.1%)		7/70 (10%)
Aspartate aminotransferase increased	2/74 (2.7%)		5/70 (7.1%)
Bacterial test positive	4/74 (5.4%)		3/70 (4.3%)
Blood bilirubin increased	3/74 (4.1%)		5/70 (7.1%)
Blood creatinine increased	12/74 (16.2%)		6/70 (8.6%)
Blood magnesium decreased	1/74 (1.4%)		4/70 (5.7%)
C-reactive protein increased	4/74 (5.4%)		5/70 (7.1%)
Epstein-Barr virus test positive	4/74 (5.4%)		2/70 (2.9%)
Neutrophil count decreased	8/74 (10.8%)		11/70 (15.7%)
Platelet count decreased	19/74 (25.7%)		21/70 (30%)
Transaminases increased	4/74 (5.4%)		6/70 (8.6%)
Weight decreased	3/74 (4.1%)		4/70 (5.7%)
White blood cell count decreased	8/74 (10.8%)		6/70 (8.6%)
Metabolism and nutrition disorders
Decreased appetite	30/74 (40.5%)		30/70 (42.9%)
Dehydration	4/74 (5.4%)		5/70 (7.1%)
Fluid overload	5/74 (6.8%)		5/70 (7.1%)
Fluid retention	6/74 (8.1%)		4/70 (5.7%)
Hyperglycaemia	12/74 (16.2%)		9/70 (12.9%)
Hyperkalaemia	5/74 (6.8%)		8/70 (11.4%)
Hypernatraemia	2/74 (2.7%)		5/70 (7.1%)
Hypoalbuminaemia	8/74 (10.8%)		2/70 (2.9%)
Hypocalcaemia	3/74 (4.1%)		5/70 (7.1%)
Hypokalaemia	24/74 (32.4%)		27/70 (38.6%)
Hypomagnesaemia	30/74 (40.5%)		35/70 (50%)
Hyponatraemia	8/74 (10.8%)		5/70 (7.1%)
Hypophagia	1/74 (1.4%)		5/70 (7.1%)
Hypophosphataemia	5/74 (6.8%)		11/70 (15.7%)
Malnutrition	4/74 (5.4%)		6/70 (8.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/74 (13.5%)		6/70 (8.6%)
Back pain	8/74 (10.8%)		12/70 (17.1%)
Bone pain	3/74 (4.1%)		4/70 (5.7%)
Musculoskeletal pain	6/74 (8.1%)		1/70 (1.4%)
Myalgia	6/74 (8.1%)		2/70 (2.9%)
Neck pain	5/74 (6.8%)		3/70 (4.3%)
Pain in extremity	5/74 (6.8%)		3/70 (4.3%)
Nervous system disorders
Dizziness	10/74 (13.5%)		8/70 (11.4%)
Dysgeusia	10/74 (13.5%)		9/70 (12.9%)
Headache	31/74 (41.9%)		23/70 (32.9%)
Restless legs syndrome	5/74 (6.8%)		1/70 (1.4%)
Somnolence	5/74 (6.8%)		2/70 (2.9%)
Tremor	10/74 (13.5%)		9/70 (12.9%)
Psychiatric disorders
Agitation	5/74 (6.8%)		3/70 (4.3%)
Anxiety	11/74 (14.9%)		9/70 (12.9%)
Confusional state	5/74 (6.8%)		3/70 (4.3%)
Delirium	4/74 (5.4%)		2/70 (2.9%)
Depression	7/74 (9.5%)		2/70 (2.9%)
Insomnia	22/74 (29.7%)		16/70 (22.9%)
Renal and urinary disorders
Acute kidney injury	17/74 (23%)		16/70 (22.9%)
Cystitis haemorrhagic	2/74 (2.7%)		4/70 (5.7%)
Dysuria	6/74 (8.1%)		5/70 (7.1%)
Haematuria	3/74 (4.1%)		4/70 (5.7%)
Pollakiuria	4/74 (5.4%)		4/70 (5.7%)
Urinary retention	4/74 (5.4%)		0/70 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	17/74 (23%)		16/70 (22.9%)
Dyspnoea	8/74 (10.8%)		12/70 (17.1%)
Epistaxis	12/74 (16.2%)		11/70 (15.7%)
Hiccups	5/74 (6.8%)		3/70 (4.3%)
Hypoxia	4/74 (5.4%)		3/70 (4.3%)
Nasal congestion	4/74 (5.4%)		1/70 (1.4%)
Oropharyngeal pain	9/74 (12.2%)		12/70 (17.1%)
Pleural effusion	4/74 (5.4%)		3/70 (4.3%)
Productive cough	5/74 (6.8%)		0/70 (0%)
Rales	4/74 (5.4%)		2/70 (2.9%)
Rhinitis allergic	2/74 (2.7%)		4/70 (5.7%)
Rhinorrhoea	6/74 (8.1%)		9/70 (12.9%)
Tachypnoea	4/74 (5.4%)		2/70 (2.9%)
Skin and subcutaneous tissue disorders
Alopecia	5/74 (6.8%)		3/70 (4.3%)
Dry skin	7/74 (9.5%)		8/70 (11.4%)
Erythema	13/74 (17.6%)		13/70 (18.6%)
Hyperhidrosis	4/74 (5.4%)		1/70 (1.4%)
Petechiae	2/74 (2.7%)		4/70 (5.7%)
Pruritus	11/74 (14.9%)		13/70 (18.6%)
Pruritus generalised	4/74 (5.4%)		5/70 (7.1%)
Rash	17/74 (23%)		19/70 (27.1%)
Rash maculo-papular	7/74 (9.5%)		7/70 (10%)
Skin hyperpigmentation	2/74 (2.7%)		5/70 (7.1%)
Vascular disorders
Flushing	4/74 (5.4%)		4/70 (5.7%)
Hypertension	25/74 (33.8%)		29/70 (41.4%)
Hypotension	13/74 (17.6%)		11/70 (15.7%)
Orthostatic hypotension	6/74 (8.1%)		3/70 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.