NCT06182410

Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy for Neuroblastoma

Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy in Patients With High-Risk Neuroblastoma Receiving Tandem Transplants

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 1 Year – 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine if administration of prophylactic defibrotide sodium (defibrotide) will prevent the development of TA-TMA in participants with high-risk neuroblastoma receiving tandem transplants compared to historic controls. SECONDARY OBJECTIVES: I. To evaluate the efficacy of defibrotide in the prevention of severe TA-TMA, as defined by any TA-TMA with one or more of the following complications: Ia. Renal failure requiring dialysis; Ib. Pleural or pericardial effusion requiring any surgical intervention; Ic. Central nervous system dysfunction, including seizure, posterior reversible encephalopathy syndrome (PRES); Id. Pulmonary hypertension; Ie. Biopsy-proven gastrointestinal involvement with bleeding; If. Death not related to relapse of underlying neuroblastoma; II. To determine the incidence of grade ≥ 3 hemorrhage (per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) in participants on prophylactic defibrotide (grade 3 hemorrhage = transfusion indicated; invasive intervention indicated; hospitalization). EXPLORATORY OBJECTIVES: I. To evaluate the incidence of hepatic sinusoidal obstructive syndrome (SOS) grade \>= 2 (per Cairo criteria) with first and second HSCT. II. To evaluate the percentage of patients who go on to second transplant compared to historic controls. III. To evaluate median time in days to start of subsequent therapy (radiation and immunotherapy) and percent of patients who have delays compared to historic controls. OUTLINE: Participants receive defibrotide intravenously (IV) over 2 hours every 6 hours (Q6H) on days -8 to +21 during their first and second HSCT in the absence of unacceptable toxicity. After completion of study treatment, participants are followed until day +42 after second transplant and then every 2 weeks until 6 months after first HSCT.

Conditions

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

Interventions

Type	Name	Description
DRUG	Defibrotide	Given intravenously (IV)

Timeline

• Start date: 2024-08-01
• Primary completion: 2027-05-31
• Completion: 2027-05-31
• First posted: 2023-12-26
• Last updated: 2024-08-07

Regulatory

• FDA-regulated drug study