Clinical trial NCT03339297: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft-versus-host Disease
Acute-graft-versus-host Disease
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-11-13
Enrollment: 152
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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).
5. Graft must be a CD3+ T-cell replete peripheral blood stem cell (PBSC) graft or non-manipulated bone marrow (BM) graft.
6. 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
11. 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).

Primary outcomes:
measure: Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT)
timeFrame: HSCT Day (Day +0 post-HSCT) through Day +100 post-HSCT
Secondary outcomes:
measure: Cumulative Incidence Percentage of Grade B to D aGvHD by Day +180 Post-HSCT
timeFrame: HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT
measure: Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by Days +100 and +180 Post-HSCT
timeFrame: HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT
measure: Cumulative Incidence Percentage of Grade C to D aGvHD by Days +100 and +180 Post-HSCT
timeFrame: HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT
measure: Cumulative Incidence Percentage of Disease Relapse by Days +100 and +180 Post-HSCT
timeFrame: HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT
measure: Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days Post-HSCT
timeFrame: HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT
measure: 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
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: Change From Baseline to Days +100 and +180 Post-HSCT in the Social/Family Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: Change From Baseline to Days +100 and +180 Post-HSCT in the Emotional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score
timeFrame: Baseline through Days +100 and +180 post HSCT
measure: 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
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: Change From Baseline to Days +100 and +180 Post-HSCT in the FACT-BMT Total Score
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: 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)
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: 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
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: 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)
timeFrame: Baseline through Days +100 and +180 post-HSCT
measure: 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
timeFrame: Baseline through Day +100 post-HSCT
measure: 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
timeFrame: Baseline through Day +180 post-HSCT
measure: 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
timeFrame: Baseline through Day +100 post-HSCT
measure: 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
timeFrame: Baseline through Day +180 post-HSCT
measure: 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
timeFrame: Baseline through Day +100 post-HSCT
measure: 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
timeFrame: Baseline through Day +180 post-HSCT
measure: 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
timeFrame: Baseline through Day +100 post-HSCT
measure: 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
timeFrame: Baseline through Day +180 post-HSCT
measure: 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
timeFrame: Baseline through Day +100 post-HSCT
measure: 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
timeFrame: Baseline through Day +180 post-HSCT
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville - PPDS
state: Florida
city: Orlando
country: United States
facility: Blood & Marrow Transplant Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Einstein Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC-Hollings Cancer Center
state: South Carolina
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Innsbruck
country: Austria
facility: Universitätsklinikum Innsbruck
city: Linz
country: Austria
facility: Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
city: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
city: Montreal
country: Canada
facility: Sainte Justine Hospital
city: Montreal
country: Canada
facility: McGill University Health Center
city: Zagreb
country: Croatia
facility: Klinichki Bolnicki Centar Zagreb
city: Clamart
country: France
facility: Hospital d Instructions des Armees Percy
city: Lille
country: France
facility: CHRU Lille
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Helios Klinikum Berlin Buch
city: Bochum
country: Germany
facility: Medizinische Universitätsklinik Knappschaftskrankenhaus
city: Brandenburg
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
city: Göttingen
country: Germany
facility: University Medicine Göttingen Germany
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
city: Köln
country: Germany
facility: Uniklinik Köln
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Mannheim
country: Germany
facility: Klinikum Mannheim Universitätsklinikum gGmbH
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Regensburg
country: Germany
facility: Klinikum der Universitat Regensburg
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Warsaw
country: Poland
facility: Centrum Onkologii im. Marii Sklodowskiej-Curie
city: Wrocław
country: Poland
facility: Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
city: Lisboa
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
city: Coruña
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital de Gran Canaria Doctor Negrin
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - H. Clinico
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
References: