Defibrotide for Prevention of Transplant Associated-Thrombotic Microangiopathy in Patients with High-Risk Neuroblastoma Undergoing Tandem Transplants

PRIMARY OBJECTIVE:

I. To determine if administration of prophylactic defibrotide sodium (defibrotide) will prevent the development of TA-TMA in patients 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 [v] 5.0) in patients 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:

Patients 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, patients are followed until day +42 after second transplant and then every 2 weeks until 6 months after first HSCT.