Defibrotide Dose-escalation for SOS Post-HSCT

Sinusoidal Obstruction Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05987124
• Other study ID #: NYMC 600
• Status: Recruiting
• Phase: Phase 2
• Start date: March 20, 2024
• Est. completion date: August 1, 2027

Study information

• Verified date: March 2024
• Source: New York Medical College
• Contact: Mitchell Cairo, MD
• Phone: 914-594-2150
• Email: mitchell_cairo[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 1, 2027
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatic Veno-Occlusive Disease
• Sinusoidal Obstruction Syndrome
• Syndrome
• Veno-occlusive Disease

Intervention

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.

Locations

Country	Name	City	State
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York Medical College

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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