An Open-Label Study of Defibrotide for the Prevention of Acute Graft-versus-Host-Disease (AGvHD)
Condition: Graft-versus-host Disease; Acute-graft-versus-host Disease
MeSH terms: Graft vs Host Disease
Intervention: Defibrotide; Standard of Care
Intervention description: 6.25 mg/kg via 2-hour IV infusion every 6 hours; Administered according to local institutional guidelines, physician preference, and patient need.
Intervention MeSH terms: Defibrotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 152.0
Sex: All
Minimum age: 1 Year
Healthy volunteers: No

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).