Table 2 Main studies on defibrotide in SOS/VOD

From: Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives—a position statement from the European Society for Blood and Marrow Transplantation (EBMT)

Reference; Phase; Number of patients

Condition

Design

Key points

Others results

Richardson et al.67

Retrospective CUP

N=19

Adult and pediatric

Severe SOS/VOD post HSCT

Compassionate use; DF: 5–60 mg/kg per day (intra-pt dose escalation, until response/toxicity)

CR: 42%

Minimal toxicity at doses tested

Day +100 survival: 32%

Richardson et al.68

Phase I/II

N=88

Adult and pediatric

Severe SOS/VOD post HSCT

Emergency use; DF: 5–60 mg/kg per day

(intra-pt dose escalation, until response/toxicity)

CR: 36%

Active dose range 25–40 mg/kg per day

Day +100 survival: 35%

No serious AEs attributed to DF

Richardson et al.57

Phase II

N=149

Adult and pediatric

Severe SOS/VOD post HSCT

Randomized, dose-finding; Arm A: DF 25 mg/kg per day

Arm B: DF 40 mg/kg per day

For 14 days or more.

Day +100 CR: 46%

Effective dose 25 mg/kg per day

Day +100 survival: 42%

Overall SAE incidence: 8%

(greater at 40 vs 25 mg/kg per day)

Richardson et al.58

Phase III

N=102

Adult and pediatric

Severe SOS/VOD post HSCT

Non-randomized, comparison with historical control; DF: 6.25 mg/kg i.v. q6h (25 mg/kg per day) for 21 days or more.

Day +100 CR

DF 24%

HC 9%

(P=0.0131)

Day +100 mortality: DF 62%; HC 75%

(P=0.0341)

Hemorrhagic AEs:

DF 65%; HC 69%

Richardson et al.59

Prospective T-IND

N=470

Adult and pediatric

SOS/VOD non-HSCT (N=45)

SOS/VOD post HSCT (N=141)

Severe SOS/VOD post HSCT (N=284)

Investigational new drug protocol; DF: 6.25 mg/kg i.v. q6h (25 mg/kg per day) for 21 days or more.

Day +100 CR

Non-HSCT 40%

SOS/VOD post HSCT 47%

Severe SOS/VOD post HSCT 29%

Day +100 survival: Non-HSCT 62%

SOS/VOD post HSCT 69%

Severe SOS/VOD post HSCT 48%

Overall hemorrhagic AEs: 18%

Corbacioglu et al.36

Phase III

N=356

Pediatric

SOS/VOD prophylaxis post HSCT

Randomized comparison; DF: 6.25 mg/kg i.v. q6h (25 mg/kg per day) from start conditioning to 30 days post HSCT (at least 14 days if discharge before).

Control: cross over to the DF arm in case of SOS/VOD onset

SOS/VOD incidence: DF 12%

Control 20% P=0.0488

Day +100 SOS/VOD related mortality: DF 2%, control 6%, P=0.10

No difference in AEs and haemorrhagic AEs

  1. Abbreviations: AE=adverse event; CUP=compassionate use program; DF=defibrotid; HC=historical control; HSCT=hematopoietic SCT; SAE=severe adverse event; SOS/VOD=sinusoidal obstruction syndrome or veno-occlusive disease; T-IND=treatment-investigational new drug.
Back to article page