search
Back to results

Defibrotide Dose-escalation for SOS Post-HSCT

Primary Purpose

Sinusoidal Obstruction Syndrome, Veno-occlusive Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Defibrotide
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sinusoidal Obstruction Syndrome

Eligibility Criteria

1 Month - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Defibrotide

    Arm Description

    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):

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    Full Information

    First Posted
    August 4, 2023
    Last Updated
    August 4, 2023
    Sponsor
    New York Medical College
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05987124
    Brief Title
    Defibrotide Dose-escalation for SOS Post-HSCT
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 1, 2023 (Anticipated)
    Primary Completion Date
    August 1, 2026 (Anticipated)
    Study Completion Date
    August 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    New York Medical College

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sinusoidal Obstruction Syndrome, Veno-occlusive Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Defibrotide
    Arm Type
    Experimental
    Arm Description
    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):
    Intervention Type
    Drug
    Intervention Name(s)
    Defibrotide
    Other Intervention Name(s)
    Defitelio
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    To determine the incidence of grade 3 or 4 adverse events related to defibrotide
    Description
    grade 3 and 4 adverse events possible or probably related to defibrotide will be collected
    Time Frame
    100 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Month
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Mitchell Cairo, MD
    Phone
    914-594-2150
    Email
    mitchell_cairo@nymc.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Lauren Harrison, MSN
    Phone
    617-285-7844
    Email
    lauren_harrison@nymc.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mitchell Cairo, MD
    Organizational Affiliation
    New York Medical College
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Defibrotide Dose-escalation for SOS Post-HSCT

    We'll reach out to this number within 24 hrs