Defibrotide for Veno-occlusive Disease

Overseen By Mitchell S Cairo, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: New York Medical College

Must be taking: Defibrotide

Must not be taking: Systemic anticoagulants

Disqualifiers: No HCT, Active bleeding, Anaphylaxis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 16 days

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on systemic anticoagulation (blood thinners).

How is the drug Defibrotide unique in treating veno-occlusive disease?

Defibrotide is unique because it is the only approved drug specifically for severe hepatic veno-occlusive disease (VOD) following stem cell transplantation, working by protecting blood vessel cells and restoring balance in blood clotting and breakdown. It is administered intravenously and has shown effectiveness in improving survival rates in patients with severe VOD. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Mitchell S Cairo, MD

Principal Investigator

New York Medical College

Eligibility Criteria

This trial is for patients aged 1 month to 75 years who have had a stem cell transplant and are suffering from sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) with kidney or lung problems. It's specifically for those not fully responding to standard defibrotide treatment or whose condition has worsened.

Inclusion Criteria

I have received a stem cell transplant.

I am between 1 month and 75 years old.

I have been diagnosed with SOS/VOD with kidney or lung issues.

Exclusion Criteria

I have not undergone a stem cell transplant.

I am currently experiencing significant bleeding.

History of development of Grade III/IV anaphylaxis probably or directly secondary to defibrotide

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intra-patient dose escalation of defibrotide every 4 days until a complete response is obtained or the highest dose level is reached

Up to 16 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

Treatment Details

Interventions

• Defibrotide

Trial Overview The study tests the safety of increasing doses of defibrotide in patients with SOS/VOD after a hematopoietic cell transplantation (HCT). The goal is to see if higher doses can be tolerated and more effective when standard treatments fail.

Participant Groups

Group I: Defibrotide Experimental Treatment 1 Intervention

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):

Defibrotide is already approved in United States, European Union for the following indications:

Approved in United States as Defitelio for:

• Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT)

Approved in European Union as Defitelio for:

• Severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT)

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Findings from Research

In a study of 23 patients undergoing hematopoietic stem cell transplantation, defibrotide was effective in treating sinusoidal obstruction syndrome (SOS/VOD), with 14 patients showing a positive response to the therapy.

Patients treated with defibrotide experienced significant improvements in symptoms and biochemical markers, including a decrease in bilirubin levels and weight, and a 70% survival rate at 100 days post-transplant, indicating its potential as a key treatment option for SOS/VOD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes. Coutsouvelis, J., Avery, S., Dooley, M., et al.[2021]

In a study of 511 stem cell transplant patients, only 1.7% developed hepatic veno-occlusive disease (VOD), and all patients treated with a low fixed dose of defibrotide (200mg twice daily for adults) experienced complete resolution of VOD without any bleeding complications.

The use of a lower dose of defibrotide was effective and safe, suggesting that it could be a viable treatment option in resource-limited settings, although further prospective studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation. Bagal, B., Chandrasekharan, A., Chougle, A., et al.[2018]

Defibrotide has been approved in the EU for treating severe hepatic veno-occlusive disease (VOD) in patients undergoing hematopoietic stem cell transplantation (HSCT), showing a significantly higher complete response rate and lower mortality at day +100 compared to historical controls.

The treatment was generally well tolerated, with no increased risk of hemorrhagic adverse events, making it a safe option for patients with severe hepatic VOD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation. Keating, GM.[2021]

Defibrotide (DF) has shown promising efficacy in treating severe hepatic veno-occlusive disease (VOD), with complete response rates between 30-60% and survival rates past day 100 ranging from 32-50% in Phase II studies.

DF may also serve as a preventive treatment for VOD in high-risk patients, highlighting its potential role in both treatment and prophylaxis for this serious complication following high-dose chemotherapy and stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of defibrotide in the treatment and prevention of veno-occlusive disease. Richardson, P., Linden, E., Revta, C., et al.[2013]

Intravenous defibrotide prophylaxis resulted in a low overall incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) at 5%, with similar rates in adults and higher rates in pediatric patients (8%).

Defibrotide significantly reduced the risk of developing VOD/SOS compared to control groups (risk ratio of 0.30), indicating it is an effective preventive treatment for patients at high risk of this condition after hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Studies of Defibrotide Prophylaxis for Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Corbacioglu, S., Topaloglu, O., Aggarwal, S.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes. [2021]

2. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Use of defibrotide in the treatment and prevention of veno-occlusive disease. [2013]

5. New Zealand pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Studies of Defibrotide Prophylaxis for Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. [2022]