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JZP963-201

AcronymISRCTNEudraCTClinicaltrials.govDRKS
JZP963-2012017-003309-16NCT03339297

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 CellTransplant

Status: Active (Recruitment Closed)

Purpose / Objectives

Primary Outcome

  • The primary objective of the study is to compare the efficacy of defibrotide
    added to standard of care immunoprophylaxis vs standard of care
    immunoprophylaxis alone for the prevention of acute graft-versus-host
    disease (aGvHD) as measured by the cumulative incidence of Grade B-D
    aGvHD by Day +100 post-allogeneic hematopoietic stem cell transplant
    (HSCT) in adult and pediatric patients.

Secondary Outcomes

  • To compare the efficacy of defibrotide added to standard of care
  • immunoprophylaxis vs standard of care immunoprophylaxis alone on
  • additional variables, as follows:
    1. Grade B-D aGvHD-free survival by Days +100 and
      +180 post-HSCT
    2. Cumulative incidence of Grade B-D aGvHD by
      Day +180 post-HSCT
    3. Cumulative incidence of Grade C-D aGvHD by Days +100 and
      +180 post-HSCT
    4. Cumulative incidence of relapse by Days +100 and +180 post-HSCT
      Note: Disease relapse per local institutional guidelines
  • To evaluate steroid use in the treatment of aGvHD by
    Day +180 post-HSCT
  • To compare the health-related quality of life (HRQoL) using the
    following questionnaires:
    1. Functional Assessment of Cancer Therapy-Bone Marrow
      Transplant-Trial Outcomes Index (FACT-BMT-TOI) (adults only)
    2. EuroQoL-5D (EQ-5D; version dependent on age group)
  • To compare the safety of defibrotide added to standard of care
    immunoprophylaxis vs standard of care immunoprophylaxis alone,
    including adverse event (AE) profile, serious adverse event (SAE)
    profile, laboratory abnormalities, neutrophil and platelet engraftment,
    graft failure, and infectious disease occurrence.

Diagnosis

Patient attributes

Age

18-99

Inclusion criteria

  • Patient must be ≥1 year and <75 years of age at screening and undergoing allogeneic HSCT.
  • Patient must be diagnosed with acute leukemia in morphologic complete remission (CR1 or CR2) or with MDS with no circulating blasts and with less than 5% blasts in the BM.
  • Patient must have planned to receive either MAC or RIC regimen (patients who receive nonmyeloablative regimens are not eligible) and have an URD who is HLA matched or singleallele mismatched (7/8 or 8/8 match at HLA-A, -B, -C, -DRB; or 9/10 or 10/10 match at HLA-A, -B, -C, -DRB, and -DQB1 at high resolution using DNA-based typing).
  • Patient 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 patient need:
    1. MTX or MMF + calcineurin inhibitor (CSA or TAC) +/- ATG (ATG use is limited to 30% of patients).
  • Patient has total bilirubin <2x the upper limit of normal (ULN; unless elevated bilirubin i  yndrome) and both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3x ULN.
  • [...]

Exclusion criteria

  • Patient has had a prior autologous or allogeneic HSCT.
  • Patient has acute bleeding that is clinically significant within 24 hours before the start of study treatment, defined as either of the following (a or b):
      1. Hemorrhage requiring >15 cc/kg of packed red blood cells (eg, pediatric patient weighing20 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
      2. Bleeding from a site which, in the investigator’s opinion, constitutes a potential lifethreatening source (eg, pulmonary hemorrhage or CNS bleeding), irrespective of amount of blood loss
    • Patient 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 (ATIII), oral anticoagulants including warfarin, and other agents that increase the risk of bleeding. Note: Heparin used to keep catheters open will be allowed (up to 100 U/kg/day).
    • 4. Patient is using or plans to use an investigational agent for the prevention of GvHD.
    • Patient is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study.
    • Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
    • [...]

Trial design

  • Phase II
  • Multicenter
  • Prospective
  • Randomized
  • Two-arm
  • Open Label

Intervention

  • The recommended treatment duration is ≥21 days beginning immediately
    prior to the start of the conditioning regimen (may have completed 1-4 doses of defibrotide prior to conditioning) and ending no later than Day +30 post-HSCT.

Documents (password protected)

Responsibilities in overall trial

Jazz Pharmaceuticals, Inc.

    Study Sites

    Klinik I für Innere Medizin

    Study office

    • Klinisches Studienzentrum der Klinik I für Innere Medizin Köln

    Status

    Active (Recruitment Closed)

    Principal Investigator

    PD Dr. Dr. med. Udo Holtick

    Deputy of Principal Investigator

    • Prof. Dr. med. Dr. h. c. Christoph Scheid
    • PD Dr. med. Marco Herling

    Contact at Site