Defibrotide Dose-escalation for SOS Post-HSCT

A Phase II Intrapatient Open-Label Dose Escalation Trial of Defibrotide in Hematopoietic Cell Transplantation (HCT) Recipients With Sinusoidal Obstructive Syndrome (SOS) Post-HCT Associated With Either Renal and/or Pulmonary Dysfunction With Either Refractory or Progressive Disease Following Defibrotide Therapy

This research study is being done to determine the safety and tolerability of increasing doses of defibrotide within a single patient with sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) after hematopoietic cell transplantation (HCT) associated with either kidney and/or lung impairment that has not obtained a complete response (CR) or progressed in severity with standard doses of defibrotide.

Study Overview

• Status: Recruiting
• Conditions: Sinusoidal Obstruction Syndrome; Veno-occlusive Disease
• Intervention / Treatment: Drug: Defibrotide

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mitchell Cairo, MD; Phone Number: 914-594-2150; Email: mitchell_cairo@nymc.edu
• Study Contact Backup: Name: Lauren Harrison, MSN; Phone Number: 617-285-7844; Email: lauren_harrison@nymc.edu

Study Locations

• United States
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • New York Medical College
      • Contact: Mitchell S Cairo, MD; Phone Number: 914-594-2150; Email: mitchell_cairo@nymc.edu
      • Principal Investigator: Mitchell S. Cairo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HCT recipients (Auto or Allograft)
• SOS/VOD as defined by Cairo/Cooke Diagnostic criteria (1) (Table 3) with either renal and/or pulmonary dysfunction as defined by Cairo/Cooke Grading criteria (1) (Appendix I).
• Unresponsive to standard defibrotide therapy as defined by at least one of the following:
• Patients with SOS/VOD failing to obtain a complete response (CR) defined by Grade I or less by Cairo/Cooke Grading criteria (1) (Appendix I). This would therefore include patients with stable disease after at least 14 days of defibrotide or partial response after at least 21 days of defibrotide (25mg/kg/day).
• Progressive disease defined by progression of at least one grade or more from diagnostic grade as defined by Cairo/Cooke Grading criteria (1) (Appendix I) following at least 7 days of defibrotide (25mg/kg/day).
• Age 1 month - 75 years

Exclusion Criteria:

• Patients who did not receive HCT.
• Concomitant systemic anticoagulation (excluding central venous line management, fibrinolytic instillation for central venous line occlusion, management of intermittent dialysis or ultrafiltration of CVVH).
• Active bleeding and/or hemorrhage of at least grade 2 and above.
• History of development of Grade III/IV anaphylaxis probably or directly secondary to defibrotide.
• Female patients who are pregnant or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Defibrotide; 7.1.1 HCT recipients with SOS/VOD and renal and/or pulmonary dysfunction with either PR after 21 days of standard doses of defibrotide (25mg/kg/day) or SD, after 14 days of standard doses of defibrotide (25mg/kg/day) progressive disease after 7 days on defibrotide (25mg/kg/day) will undergo intra-patient dose escalation every 4 days until a complete response is obtained up until the highest dose level of 100mg/kg/day at which point an endpoint of CR, PR or SD will be sought (see 7.2 for definition of response) (Maximum of 4 dose levels) (7.1.2):

Drug: Defibrotide; HCT recipients with SOS/VOD and renal and/or pulmonary dysfunction with either PR after 21 days of standard doses of defibrotide (25mg/kg/day) or SD, after 14 days of standard doses of defibrotide (25mg/kg/day) progressive disease after 7 days on defibrotide (25mg/kg/day) will undergo intra-patient dose escalation every 4 days until a complete response is obtained up until the highest dose level of 100mg/kg/day at which point an endpoint of CR, PR or SD will be sought(Maximum of 4 dose levels). Defibrotide will be administered in D5W or 0.9% NaCl via IV infusion over 2 hours q6 hours.; Other Names: Defitelio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the incidence of grade 3 or 4 adverse events related to defibrotide	grade 3 and 4 adverse events possible or probably related to defibrotide will be collected	100 days

Collaborators and Investigators

• Sponsor: New York Medical College
• Investigators: Principal Investigator: Mitchell Cairo, MD, New York Medical College

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: August 4, 2023
• First Submitted That Met QC Criteria: August 4, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Liver Diseases; Syndrome; Hepatic Veno-Occlusive Disease; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Defibrotide
• Other Study ID Numbers: NYMC 600

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No