Defibrotide Dose-escalation for SOS Post-HSCT

NCT05987124 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NYMC 600
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sinusoidal Obstruction Syndrome; Veno-occlusive Disease

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Defibrotide

EXPERIMENTAL

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

Interventions

Defibrotide DRUG

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.

Also known as: Defitelio

Defibrotide

Eligibility Criteria

• Age: 1 Month - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York Medical College: lead

Study Sites (1)

New York Medical College

Vallhala, New York, 10595, United States

RECRUITING

MeSH Terms

Conditions

Hepatic Veno-Occlusive Disease

Interventions

defibrotide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Mitchell Cairo, MD

  New York Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mitchell Cairo, MD

CONTACT

914-594-2150; mitchell_cairo@nymc.edu

Lauren Harrison, MSN

CONTACT

617-285-7844; lauren_harrison@nymc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 14, 2023
• Study Start: March 20, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)