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

Primary Purpose

Graft-versus-host Disease, Acute-graft-versus-host Disease

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Defibrotide

Standard of Care

About this trial

This is an interventional treatment trial for Graft-versus-host Disease

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant must be ≥1 year of age at screening and undergoing allogeneic Hematopoietic Stem Cell Transplant (HSCT).
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
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
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).
Graft must be a CD3+ T-cell replete peripheral blood stem cell (PBSC) graft or non-manipulated bone marrow (BM) graft.
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:

Participant has had a prior autologous or allogeneic HSCT.
Participant is using or plans to use an investigational agent for the prevention of GvHD.
Participant is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study.
Participant, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
Participant has a psychiatric illness that would prevent the participant or legal guardian or representative from giving informed consent and/or assent.
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.
Participant is pregnant or lactating and does not agree to stop breastfeeding.
Any other condition that would cause a risk to the participant if he/she participated in the trial.
Participant has a known history of hypersensitivity to defibrotide or any of the excipients.
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
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).

Sites / Locations

USC Norris Cancer Center
Mattel Children's Hospital UCLA
Stanford University
University of California, San Francisco Medical Center
Mayo Clinic Jacksonville - PPDS
Blood & Marrow Transplant Center
Emory University Hospital
Northwestern Memorial Hospital
University of Kansas Medical Center
James Graham Brown Cancer Center
Ochsner Clinic Foundation
University of Nebraska Medical Center
Montefiore Einstein Cancer Center
University of North Carolina at Chapel Hill
Penn State Milton S Hershey Medical Center
MUSC-Hollings Cancer Center
VA Puget Sound Health Care System
West Virginia University Hospital
Universitätsklinikum Innsbruck
Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH
Cliniques Universitaires Saint-Luc
UZ Gent
UZ Leuven
Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
Hôpital Maisonneuve-Rosemont
Sainte Justine Hospital
McGill University Health Center
Klinichki Bolnicki Centar Zagreb
Hospital d Instructions des Armees Percy
CHRU Lille
Institut Universitaire du Cancer de Toulouse - Oncopole
Institut Gustave Roussy
Helios Klinikum Berlin Buch
Medizinische Universitätsklinik Knappschaftskrankenhaus
Klinikum Frankfurt (Oder) GmbH
Universitätsklinikum Carl Gustav Carus an der TU Dresden
University Medicine Göttingen Germany
Universitaetsklinikum Halle (Saale)
Uniklinik Köln
Universitatsklinikum Leipzig
Klinikum Mannheim Universitätsklinikum gGmbH
Klinikum rechts der Isar der Technischen Universität München
Klinikum der Universitat Regensburg
Attikon University General Hospital
University General Hospital of Patras
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
Azienda Ospedaliero Universitaria di Parma
Ospedale Pediatrico Bambino Gesù
Centrum Onkologii im. Marii Sklodowskiej-Curie
Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
Hospital Universitario Marques de Valdecilla
Hospital de Gran Canaria Doctor Negrin
Hospital Universitario Puerta de Hierro - Majadahonda
Complejo Asistencial Universitario de Salamanca - H. Clinico
Hospital Universitario Virgen del Rocio
Hospital Clinico Universitario de Valencia
Birmingham Heartlands Hospital
St James University Hospital
St. James University Hospital
Leicester Royal Infirmary
Manchester Royal Infirmary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Defibrotide Prophylaxis

Standard of Care

Arm Description

Standard of Care Immunoprophylaxis + Defibrotide

Standard of Care Immunoprophylaxis Alone

Outcomes

Primary Outcome Measures

Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (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

Cumulative Incidence Percentage of Grade B to D aGvHD by 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.

Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by 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.

Cumulative Incidence Percentage of Grade C to D aGvHD by 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.

Cumulative Incidence Percentage of Disease Relapse by 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.

Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days 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.

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

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.

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

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.

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

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.

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

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.

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

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.

Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score

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.

Change From Baseline to Days +100 and +180 Post-HSCT in the FACT-BMT Total Score

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.

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)

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.

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

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.

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)

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.

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

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.

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

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.

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

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.

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

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.

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

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

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.

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

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

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.

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

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

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.

Full Information

NCT ID

NCT03339297

First Posted

November 8, 2017

Last Updated

July 26, 2021

Sponsor

Jazz Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03339297

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

February 21, 2018 (Actual)

Primary Completion Date

May 12, 2020 (Actual)

Study Completion Date

May 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Jazz Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft-versus-host Disease, Acute-graft-versus-host Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

152 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Defibrotide Prophylaxis

Arm Type

Experimental

Arm Description

Standard of Care Immunoprophylaxis + Defibrotide

Arm Title

Standard of Care

Arm Type

Active Comparator

Arm Description

Standard of Care Immunoprophylaxis Alone

Intervention Type

Drug

Intervention Name(s)

Defibrotide

Intervention Description

6.25 mg/kg via 2-hour IV infusion every 6 hours

Intervention Type

Drug

Intervention Name(s)

Standard of Care

Intervention Description

Administered according to local institutional guidelines, physician preference, and patient need.

Primary Outcome Measure Information:

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

Time Frame

HSCT Day (Day +0 post-HSCT) through Day +100 post-HSCT

Secondary Outcome Measure Information:

Title

Cumulative Incidence Percentage of Grade B to D aGvHD by Day +180 Post-HSCT

Description

Time Frame

HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT

Title

Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by Days +100 and +180 Post-HSCT

Description

Time Frame

HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT

Title

Cumulative Incidence Percentage of Grade C to D aGvHD by Days +100 and +180 Post-HSCT

Description

Time Frame

HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT

Title

Cumulative Incidence Percentage of Disease Relapse by Days +100 and +180 Post-HSCT

Description

Time Frame

HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT

Title

Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days Post-HSCT

Description

Time Frame

HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT

Title

Description

Time Frame

Baseline through Days +100 and +180 post-HSCT

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

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

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

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

Title

Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score

Description

Time Frame

Baseline through Days +100 and +180 post-HSCT

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

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

Time Frame

Baseline through Days +100 and +180 post-HSCT

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

Time Frame

Baseline through Days +100 and +180 post-HSCT

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

Time Frame

Baseline through Days +100 and +180 post-HSCT

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

Time Frame

Baseline through Day +100 post-HSCT

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

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

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

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

Time Frame

Baseline through Day +100 post-HSCT

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

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

Time Frame

Baseline through Day +100 post-HSCT

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

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

Time Frame

Baseline through Day +100 post-HSCT

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant must be ≥1 year of age at screening and undergoing allogeneic Hematopoietic Stem Cell Transplant (HSCT). 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 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 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). Graft must be a CD3+ T-cell replete peripheral blood stem cell (PBSC) graft or non-manipulated bone marrow (BM) graft. 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: Participant has had a prior autologous or allogeneic HSCT. Participant is using or plans to use an investigational agent for the prevention of GvHD. Participant is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study. Participant, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. Participant has a psychiatric illness that would prevent the participant or legal guardian or representative from giving informed consent and/or assent. 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. Participant is pregnant or lactating and does not agree to stop breastfeeding. Any other condition that would cause a risk to the participant if he/she participated in the trial. Participant has a known history of hypersensitivity to defibrotide or any of the excipients. 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 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).

Facility Information:

Facility Name

USC Norris Cancer Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

Mattel Children's Hospital UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Stanford University

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

University of California, San Francisco Medical Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Mayo Clinic Jacksonville - PPDS

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

Facility Name

Blood & Marrow Transplant Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32804

Country

United States

Facility Name

Emory University Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Northwestern Memorial Hospital

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of Kansas Medical Center

City

Westwood

State/Province

Kansas

ZIP/Postal Code

66205

Country

United States

Facility Name

James Graham Brown Cancer Center

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Ochsner Clinic Foundation

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70121

Country

United States

Facility Name

University of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

Facility Name

Montefiore Einstein Cancer Center

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27514

Country

United States

Facility Name

Penn State Milton S Hershey Medical Center

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Facility Name

MUSC-Hollings Cancer Center

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

VA Puget Sound Health Care System

City

Seattle

State/Province

Washington

ZIP/Postal Code

98108

Country

United States

Facility Name

West Virginia University Hospital

City

Morgantown

State/Province

West Virginia

ZIP/Postal Code

26506

Country

United States

Facility Name

Universitätsklinikum Innsbruck

City

Innsbruck

ZIP/Postal Code

6020

Country

Austria

Facility Name

Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH

City

Linz

ZIP/Postal Code

4020

Country

Austria

Facility Name

Cliniques Universitaires Saint-Luc

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Specialized Hospital for Active Treatment of Haematological Diseases - Sofia

City

Sofia

ZIP/Postal Code

1756

Country

Bulgaria

Facility Name

Hôpital Maisonneuve-Rosemont

City

Montreal

ZIP/Postal Code

H1T 2M4

Country

Canada

Facility Name

Sainte Justine Hospital

City

Montreal

ZIP/Postal Code

H3T 1C5

Country

Canada

Facility Name

McGill University Health Center

City

Montreal

ZIP/Postal Code

H4A 3J1

Country

Canada

Facility Name

Klinichki Bolnicki Centar Zagreb

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Hospital d Instructions des Armees Percy

City

Clamart

ZIP/Postal Code

92141

Country

France

Facility Name

CHRU Lille

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Institut Universitaire du Cancer de Toulouse - Oncopole

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

Institut Gustave Roussy

City

Villejuif

ZIP/Postal Code

94805

Country

France

Facility Name

Helios Klinikum Berlin Buch

City

Berlin

ZIP/Postal Code

13125

Country

Germany

Facility Name

Medizinische Universitätsklinik Knappschaftskrankenhaus

City

Bochum

ZIP/Postal Code

44892

Country

Germany

Facility Name

Klinikum Frankfurt (Oder) GmbH

City

Brandenburg

ZIP/Postal Code

15236

Country

Germany

Facility Name

Universitätsklinikum Carl Gustav Carus an der TU Dresden

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

University Medicine Göttingen Germany

City

Göttingen

ZIP/Postal Code

37075

Country

Germany

Facility Name

Universitaetsklinikum Halle (Saale)

City

Halle

ZIP/Postal Code

06120

Country

Germany

Facility Name

Uniklinik Köln

City

Köln

ZIP/Postal Code

50937

Country

Germany

Facility Name

Universitatsklinikum Leipzig

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Klinikum Mannheim Universitätsklinikum gGmbH

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

Klinikum rechts der Isar der Technischen Universität München

City

Munchen

ZIP/Postal Code

81675

Country

Germany

Facility Name

Klinikum der Universitat Regensburg

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

Attikon University General Hospital

City

Athens

ZIP/Postal Code

12462

Country

Greece

Facility Name

University General Hospital of Patras

City

Patras

ZIP/Postal Code

26500

Country

Greece

Facility Name

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda

City

Milano

ZIP/Postal Code

20162

Country

Italy

Facility Name

Azienda Ospedaliero Universitaria di Parma

City

Parma

ZIP/Postal Code

41236

Country

Italy

Facility Name

Ospedale Pediatrico Bambino Gesù

City

Roma

ZIP/Postal Code

00165

Country

Italy

Facility Name

Centrum Onkologii im. Marii Sklodowskiej-Curie

City

Warsaw

ZIP/Postal Code

00-001

Country

Poland

Facility Name

Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku

City

Wrocław

ZIP/Postal Code

53-439

Country

Poland

Facility Name

Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

City

Lisboa

ZIP/Postal Code

1099

Country

Portugal

Facility Name

Hospital Universitario Marques de Valdecilla

City

Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

Hospital de Gran Canaria Doctor Negrin

City

Las Palmas De Gran Canaria

ZIP/Postal Code

35010

Country

Spain

Facility Name

Hospital Universitario Puerta de Hierro - Majadahonda

City

Madrid

ZIP/Postal Code

28222

Country

Spain

Facility Name

Complejo Asistencial Universitario de Salamanca - H. Clinico

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Hospital Universitario Virgen del Rocio

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

Hospital Clinico Universitario de Valencia

City

Valencia

ZIP/Postal Code

41013

Country

Spain

Facility Name

Birmingham Heartlands Hospital

City

Birmingham

ZIP/Postal Code

B9 5SS

Country

United Kingdom

Facility Name

St James University Hospital

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

St. James University Hospital

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Leicester Royal Infirmary

City

Leicester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

Manchester Royal Infirmary

City

Manchester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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