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

NCT03339297 | Completed Phase 2 Results FDA Drug

• 1 other identifier: JZP963-201
• Study Type: interventional
• Target: 152
• Locations: 14 countries
• Sites: 62

Brief Summary

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

Conditions

Graft-versus-host Disease; Acute-graft-versus-host Disease

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (25)

• 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

• 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

• 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 Disease Relapse by Days +100 and +180 Post-HSCT

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

• 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

Study Arms (2)

Defibrotide Prophylaxis

EXPERIMENTAL

Standard of Care Immunoprophylaxis + Defibrotide

Drug: Defibrotide; Drug: Standard of Care

Standard of Care

ACTIVE COMPARATOR

Standard of Care Immunoprophylaxis Alone

Drug: Standard of Care

Interventions

Defibrotide DRUG

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

Defibrotide Prophylaxis

Standard of Care DRUG

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

Defibrotide Prophylaxis; Standard of Care

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (62)

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

Mattel Children's Hospital UCLA

Los Angeles, California, 90095, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224, United States

Location

Blood & Marrow Transplant Center

Orlando, Florida, 32804, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Montefiore Einstein Cancer Center

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MUSC-Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

Universitätsklinikum Innsbruck

Innsbruck, 6020, Austria

Location

Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH

Linz, 4020, Austria

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Specialized Hospital for Active Treatment of Haematological Diseases - Sofia

Sofia, 1756, Bulgaria

Location

Hôpital Maisonneuve-Rosemont

Montreal, H1T 2M4, Canada

Location

Sainte Justine Hospital

Montreal, H3T 1C5, Canada

Location

McGill University Health Center

Montreal, H4A 3J1, Canada

Location

Klinichki Bolnicki Centar Zagreb

Zagreb, 10000, Croatia

Location

Hospital d Instructions des Armees Percy

Clamart, 92141, France

Location

CHRU Lille

Lille, 59037, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Helios Klinikum Berlin Buch

Berlin, 13125, Germany

Location

Medizinische Universitätsklinik Knappschaftskrankenhaus

Bochum, 44892, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Brandenburg, 15236, Germany

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

University Medicine Göttingen Germany

Göttingen, 37075, Germany

Location

Universitaetsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum Mannheim Universitätsklinikum gGmbH

Mannheim, 68167, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Klinikum der Universitat Regensburg

Regensburg, 93053, Germany

Location

Attikon University General Hospital

Athens, 12462, Greece

Location

University General Hospital of Patras

Pátrai, 26500, Greece

Location

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

Milan, 20162, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 41236, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

Location

Centrum Onkologii im. Marii Sklodowskiej-Curie

Warsaw, 00-001, Poland

Location

Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku

Wroclaw, 53-439, Poland

Location

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

Lisbon, 1099, Portugal

Location

Hospital Universitario Marques de Valdecilla

A Coruña, 15006, Spain

Location

Hospital de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28222, Spain

Location

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 41013, Spain

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

St. James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Manchester Royal Infirmary

Manchester, LE1 5WW, United Kingdom

Location

Related Publications (1)

• Hudspeth M, Mori S, Nachbaur D, Perez-Simon JA, Stolzel F, Riches M, Wu W, Zhang P, Agarwal S, Yakoub-Agha I. A phase II, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Haematologica. 2023 Apr 1;108(4):1026-1038. doi: 10.3324/haematol.2022.281471.

  PMID: 36519326 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

defibrotide; Standard of Care

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Director, Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-870-9177

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 13, 2017
• Study Start: February 21, 2018
• Primary Completion: May 12, 2020
• Study Completion: May 12, 2020
• Last Updated: August 18, 2021
• Results First Posted: August 18, 2021

Record last verified: 2021-07

Locations

FR (4); IT (3); GR (2); PT (1); GB (5); BE (3); US (18); PL (2); ES (6); CA (3); CR (1); AU (2); DE (11); BU (1)