Defibrotide Dose-escalation for SOS Post-HSCT

Phase 2

Recruiting

• Conditions: Sinusoidal Obstruction Syndrome; Veno-occlusive Disease
• Interventions: Drug: Defibrotide

• Registration Number: NCT05987124
• Lead Sponsor: New York Medical College

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-04
• Study First Submitted QC: 2023-08-04
• Study First Posted: 2023-08-14
• Status Verified: 2024-03
• Study Start: 2024-03-20
• Last Update Submitted: 2024-03-22
• Last Update Posted: 2024-03-26
• Primary Completion: 2026-08-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Defibrotide	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):

Primary Outcome Measures

Name	Time	Method
To determine the incidence of grade 3 or 4 adverse events related to defibrotide	100 days	grade 3 and 4 adverse events possible or probably related to defibrotide will be collected

Trial Locations

Locations (1)

New York Medical College; 🇺🇸 Valhalla, New York, United States