Definitions of ruxolitinib failure used in phase 2 and 3 clinical trials
| Failure feature* . | Definition . | Phase 2/3 trial(s) . |
|---|---|---|
| Ruxolitinib duration | At least 14 d (less if intolerability or allergy) | JAKARTA II (NCT01523171) |
| At least 28 d | SIMPLIFY 2 (NCT02101268) | |
| ≥3 mo (if initial response was observed) or ≥28 d (if transfusion, hemorrhage, or cytopenias) | PAC203 (NCT03165734) | |
| Ruxolitinib dose | <20 mg twice daily | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Spleen response | Increase in spleen volume of ≥25% from nadir, splenic irradiation or splenectomy | COMFORT II (NCT00934544) |
| <10% spleen volume reduction by magnetic resonance imaging or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters after an initial response | PAC203 (NCT03165734) | |
| Red blood cell transfusions | Required red blood cell transfusions (at least 2 U/mo for 2 mo in PAC203) | PAC203 (NCT03165734) |
| SIMPLIFY 2 (NCT02101268) | ||
| Thrombocytopenia | CTCAE grade ≥3 | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Anemia | CTCAE grade ≥3 | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Hemorrhage or hematoma | CTCAE grade ≥3 (or bleeding) | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Progression | Peripheral blood blast percentage ≥20% sustained for ≥8 wk or bone marrow blast count ≥20% | COMFORT II (NCT00934544) |
| Failure feature* . | Definition . | Phase 2/3 trial(s) . |
|---|---|---|
| Ruxolitinib duration | At least 14 d (less if intolerability or allergy) | JAKARTA II (NCT01523171) |
| At least 28 d | SIMPLIFY 2 (NCT02101268) | |
| ≥3 mo (if initial response was observed) or ≥28 d (if transfusion, hemorrhage, or cytopenias) | PAC203 (NCT03165734) | |
| Ruxolitinib dose | <20 mg twice daily | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Spleen response | Increase in spleen volume of ≥25% from nadir, splenic irradiation or splenectomy | COMFORT II (NCT00934544) |
| <10% spleen volume reduction by magnetic resonance imaging or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters after an initial response | PAC203 (NCT03165734) | |
| Red blood cell transfusions | Required red blood cell transfusions (at least 2 U/mo for 2 mo in PAC203) | PAC203 (NCT03165734) |
| SIMPLIFY 2 (NCT02101268) | ||
| Thrombocytopenia | CTCAE grade ≥3 | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Anemia | CTCAE grade ≥3 | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Hemorrhage or hematoma | CTCAE grade ≥3 (or bleeding) | SIMPLIFY 2 (NCT02101268) |
| PAC203 (NCT03165734) | ||
| Progression | Peripheral blood blast percentage ≥20% sustained for ≥8 wk or bone marrow blast count ≥20% | COMFORT II (NCT00934544) |
CTCAE, Common Terminology Criteria for Adverse Events.
Inadequate or recurrent symptom response criteria not defined in previous clinical trials, although symptom response has been defined as ≥50% reduction in the pretreatment Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.21