Table 2. Main studies on defibrotide in SOS/VOD.
| 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 |
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.