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

NCT ID: NCT03339297

Last Updated: 2021-08-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-21

Study Completion Date

2020-05-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Defibrotide Prophylaxis

Standard of Care Immunoprophylaxis + Defibrotide

Group Type EXPERIMENTAL

Defibrotide

Intervention Type DRUG

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

Standard of Care

Intervention Type DRUG

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

Standard of Care

Standard of Care Immunoprophylaxis Alone

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Defibrotide

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

Intervention Type DRUG

Standard of Care

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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).
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

USC Norris Cancer Center

Los Angeles, California, United States

Site Status

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California, San Francisco Medical Center

San Francisco, California, United States

Site Status

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, United States

Site Status

Blood & Marrow Transplant Center

Orlando, Florida, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Westwood, Kansas, United States

Site Status

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Montefiore Einstein Cancer Center

The Bronx, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

MUSC-Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

VA Puget Sound Health Care System

Seattle, Washington, United States

Site Status

West Virginia University Hospital

Morgantown, West Virginia, United States

Site Status

Universitätsklinikum Innsbruck

Innsbruck, , Austria

Site Status

Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH

Linz, , Austria

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Specialized Hospital for Active Treatment of Haematological Diseases - Sofia

Sofia, , Bulgaria

Site Status

Hôpital Maisonneuve-Rosemont

Montreal, , Canada

Site Status

Sainte Justine Hospital

Montreal, , Canada

Site Status

McGill University Health Center

Montreal, , Canada

Site Status

Klinichki Bolnicki Centar Zagreb

Zagreb, , Croatia

Site Status

Hospital d Instructions des Armees Percy

Clamart, , France

Site Status

CHRU Lille

Lille, , France

Site Status

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Helios Klinikum Berlin Buch

Berlin, , Germany

Site Status

Medizinische Universitätsklinik Knappschaftskrankenhaus

Bochum, , Germany

Site Status

Klinikum Frankfurt (Oder) GmbH

Brandenburg, , Germany

Site Status

Uniklinik Köln

Cologne, , Germany

Site Status

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, , Germany

Site Status

University Medicine Göttingen Germany

Göttingen, , Germany

Site Status

Universitaetsklinikum Halle (Saale)

Halle, , Germany

Site Status

Universitatsklinikum Leipzig

Leipzig, , Germany

Site Status

Klinikum Mannheim Universitätsklinikum gGmbH

Mannheim, , Germany

Site Status

Klinikum rechts der Isar der Technischen Universität München

München, , Germany

Site Status

Klinikum der Universitat Regensburg

Regensburg, , Germany

Site Status

Attikon University General Hospital

Athens, , Greece

Site Status

University General Hospital of Patras

Pátrai, , Greece

Site Status

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

Milan, , Italy

Site Status

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Site Status

Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Site Status

Centrum Onkologii im. Marii Sklodowskiej-Curie

Warsaw, , Poland

Site Status

Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku

Wroclaw, , Poland

Site Status

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

Lisbon, , Portugal

Site Status

Hospital Universitario Marques de Valdecilla

A Coruña, , Spain

Site Status

Hospital de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, , Spain

Site Status

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, , Spain

Site Status

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

St James University Hospital

Leeds, , United Kingdom

Site Status

St. James University Hospital

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Austria Belgium Bulgaria Canada Croatia France Germany Greece Italy Poland Portugal Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 36519326 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

JZP963-201

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Keratinocyte Growth Factor to Prevent Acute GVHD
NCT00031148 COMPLETED PHASE1/PHASE2