Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy for Neuroblastoma

NCT06182410 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 230822NCI-2023-10277
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests how well defibrotide works in preventing transplant-associated thrombotic microangiopathy (TA-TMA) in patients with high-risk neuroblastoma undergoing tandem transplants (hematopoietic stem cell transplant \[HSCT\]). TMA is a potential life-threatening complication of stem cell transplant. TMA is a possible side effect of the chemotherapy (conditioning regimen) patients receive to help treat high-risk neuroblastoma, because these medicines can sometimes damage the blood vessel walls in the body. This damage leads to formation of tiny blood clots in organs, especially the kidney. This then causes organ damage and leads to problems with how they function. This study may help researchers learn how defibrotide may help prevent TMA before it starts, or help treat it once it starts among patients with high-risk neuroblastoma undergoing tandem transplants.

Conditions

Transplant-Associated Thrombotic Microangiopathy; Neuroblastoma; High-risk Neuroblastoma; Thrombotic Microangiopathies

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of transplant-associated thrombotic microangiopathy (TA-TMA)

  The cumulative incidence of TA-TMA in participants will be compared to historical controls. The historic controls will be participants with high-risk neuroblastoma who underwent planned tandem transplant at University of California San Francisco (UCSF) between 2017 and 2023.

  Up to1 year

Secondary Outcomes (1)

• Cumulative incidence of severe TA-TMA

  Up to 1 year

Study Arms (1)

Supportive Care (defibrotide)

EXPERIMENTAL

Participants receive defibrotide IV over 2 hours every six hours on days -8 to +21 during the first and second rounds of Hematopoietic stem-cell transplantation (HSCT).

Drug: Defibrotide

Interventions

Defibrotide DRUG

Given intravenously (IV)

Also known as: Noravid

Supportive Care (defibrotide)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: 1 - \< 18 years old.
• Participants must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at the time of initial diagnosis. Participants who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
• Participants may have had salvage therapies (i.e., meta-iodobenzylguanidine (MIBG), dinutuximab) after induction but cannot have progressive disease at start of 4.
• Planned tandem transplants with conditioning with cyclophosphamide-thiotepa and carboplatin-etoposide-melphalan on, or as per, NCT03126916 (ANBL1531) or other tandem-containing COG high-risk neuroblastoma trials.
• Participants may be enrolled in upfront neuroblastoma protocol, but this is not required.
• Upfront MIBG or other therapies is not a contraindication.
• Organ function per institutional standard of care (SOC) guiding clearance for autologous HSCT.
• Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability for subject to comply with the requirements of the study.

You may not qualify if:

• Life expectancy \< 6 months.
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Known bleeding diathesis or bleeding risk deemed by the treating physician to be a contraindication to administration of defibrotide or on concomitant therapeutic anticoagulation. Administration of heparin and/or alteplase for central line maintenance is allowed.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Jazz Pharmaceuticals: collaborator

MeSH Terms

Conditions

Neuroblastoma; Thrombotic Microangiopathies

Interventions

defibrotide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Study Officials

• Christine Higham, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: December 26, 2023
• Study Start: August 1, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share