Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients

NCT00358501 | Completed Phase 3 Results DMC

• 1 other identifier: 2005-01
• Study Type: interventional
• Target: 134
• Locations: 2 countries
• Sites: 25

Brief Summary

The purpose of this study is to (1) demonstrate the efficacy and safety (toxicity) of 25 mg/kg/day of Defibrotide in patients with severe veno-occlusive disease (sVOD) and (2) evaluate serum and endothelial markers of veno-occlusive disease (VOD) through the analysis of blood samples.

Conditions

Severe Hepatic Veno-Occlusive Disease

Keywords

Defibrotide; Severe veno occlusive disease; Multi organ failure; Stem cell transplant; Liver; Regimen related toxicity; Day 100 survival

Outcome Measures

Primary Outcomes (2)

• Survival at Day+100 Following Hematopoietic Stem Cell Transplant

  The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.

  Day+100 post hematopoietic stem cell transplant

• Complete Response by Day+100 Post Hematopoietic Stem Cell Transplant

  The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.

  Day+100 post hematopoietic stem cell transplant

Secondary Outcomes (2)

• Survival at Day+180 Post Hematopoietic Stem Cell Transplantation

  180 days post hematopoietic stem cell transplant

• Percentage of Participants With Treatment-Emergent Adverse Events

  Through 30 days from the last dose of Defibrotide

Other Outcomes (1)

• Historical Control Group Adverse Event Information

  Through 30 days from the last dose of Defibrotide

Study Arms (2)

Defibrotide

EXPERIMENTAL

Defibrotide treatment

Drug: Defibrotide

Historical Control

NO INTERVENTION

Historical control group

Interventions

Defibrotide DRUG

Defibrotide 6.25 mg/kg i.v. administered four times a day via 2 hour continuous infusion. Minimum duration 21 days.

Defibrotide

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of VOD, defined by jaundice (bilirubin \>/= 2 mg/dL) and at least 2 of the following clinical findings, by Day+21 post stem cell transplant: ascites; weight gain \>/= 5% above baseline weight; hepatomegaly.
• Severe VOD, defined as VOD with multi-organ failure, i.e., presence of one or both of the following, by Day+28 post stem cell transplant: renal or pulmonary dysfunction.
• Provide voluntary written informed consent.

You may not qualify if:

• Pre-existing (prior to SCT) cirrhosis
• An alternative diagnosis for weight gain, ascites and jaundice
• Graft-versus-host disease (GVHD) grade B or higher involving liver or gut or grade C or higher involving skin
• Prior solid organ transplant
• Dependent on dialysis prior to and/or at the time of SCT
• Dependent on oxygen supplementation prior to SCT
• Significant acute bleeding or hemodynamic instability
• Requirement for the use of any medications that increase risk of hemorrhage will be excluded from the treatment group

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (25)

Unknown Facility

Duarte, California, United States

Location

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Palo Alto, California, United States

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Denver, Colorado, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Maywood, Illinois, United States

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Indianapolis, Indiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Hackensack, New Jersey, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

Location

Related Publications (3)

• Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, Elias AD, Antin JH, Soiffer R, Spitzer T, Avigan D, Bearman SI, Martin PL, Kurtzberg J, Vredenburgh J, Chen AR, Arai S, Vogelsang G, McDonald GB, Guinan EC. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood. 2002 Dec 15;100(13):4337-43. doi: 10.1182/blood-2002-04-1216. Epub 2002 Aug 1.

  PMID: 12393437 BACKGROUND

• Richardson, Soiffer, Antin, Voss, Jin, Kurtzberget al. Defibrotide (DF) for the Treatment of Severe Veno-Occlusive Disease (VOD) and Multi-System Organ Failure (MOF) Post SCT: Final Results of a Phase II, Multicenter, Randomized Study and Preliminary Analyses of Surrogate Markers and Ultrasound Findings. [abstract]. Blood. 2004;104 (11).

  BACKGROUND

• Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, Arai S, Grupp SA, Guinan EC, Martin PL, Steinbach G, Krishnan A, Nemecek ER, Giralt S, Rodriguez T, Duerst R, Doyle J, Antin JH, Smith A, Lehmann L, Champlin R, Gillio A, Bajwa R, D'Agostino RB Sr, Massaro J, Warren D, Miloslavsky M, Hume RL, Iacobelli M, Nejadnik B, Hannah AL, Soiffer RJ. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016 Mar 31;127(13):1656-65. doi: 10.1182/blood-2015-10-676924. Epub 2016 Jan 29.

  PMID: 26825712 DERIVED

Related Links

• Click here for more information about Defibrotide.

MeSH Terms

Conditions

Hepatic Veno-Occlusive Disease; Multiple Organ Failure

Interventions

defibrotide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases; Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Primary endpoint was changed after all patients were treated and current results reflect the final protocol. Adverse event severity was only reported for treatment group as control group was not assessed for severity.

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Jazz Pharmaceuticals

650.496.3777

Study Officials

• Paul Richardson, M.D.

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2006
• First Posted: August 1, 2006
• Study Start: July 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: March 1, 2015
• Last Updated: January 30, 2017
• Results First Posted: January 30, 2017

Record last verified: 2016-12

Locations

US (22); CA (3)