Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia

Exclusion Criteria

• •Active malignancy diagnosed within the past 2 years, except for curatively treated non-invasive cancers (e.g., basal/squamous cell skin cancer, low-risk prostate cancer on stable endocrine therapy with PSA stable ≥3 months).
• •Allogeneic hematopoietic stem cell transplant within 12 months prior to enrollment, or requiring immunosuppressive therapy within 6 months before enrollment.
• •Likely to undergo allogeneic hematopoietic stem cell transplant within 6 months, per investigator assessment.
• •Prior systemic treatment with any JAK inhibitor.
• •Treatment with hypomethylating agents or cytotoxic chemotherapy (excluding hydroxyurea) within 28 days prior to enrollment.
• •Participation in another interventional study or use of experimental therapy within 28 days or 5 half-lives, whichever is longer.
• •Use of hematologic support drugs within 28 days prior to enrollment. Supportive care permitted.
• •Use of strong CYP3A4 inhibitors or inducers within 14 days or 5 half-lives before enrollment, whichever is shorter.
• •Use of systemic anticoagulants or antiplatelets (except aspirin ≤100 mg/day) within 14 days prior. Therapeutic anticoagulation allowed if stable for ≥90 days without bleeding events.
• •CTCAE Grade ≥2 bleeding within 3 months prior to enrollment, unless due to a reversible cause (e.g., trauma, surgery).
• •QTcF \>450 ms (men) or \>470 ms (women); QTcF up to 480 ms allowed if QRS \>100 ms. QTcF may be repeated if affected by reversible factors.
• •CTCAE Grade ≥3 cardiac event within 3 months before enrollment.
• •Symptomatic heart failure with limitations on ordinary activity.
• •Uncontrolled infection at study entry.
• •Moderate/severe hepatic impairment (Child-Pugh B or C), or active viral hepatitis:
• •HBV: Exclude if HBsAg+ or HBV DNA detectable. HBV antiviral therapy allowed if HBV DNA undetectable.
• •HCV: Allowed if HCV Ab+ but RNA negative.
• •Uncontrolled HIV or detectable viral load while on antiretrovirals.
• •Known hypersensitivity to pacritinib or its excipients (microcrystalline cellulose, polyethylene glycol, magnesium stearate).