This is a prospective, open-label phase 1b/2 clinical trial to explore the safety and efficacy profiles of baricitinib in patients with thrombopoietin-receptor-agonist-refractory persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation.

Phase 1 part:

The phase 1b part will use a standard 3+3 design to explore the safety profiles and to establish the recommended phase 2 dose (RP2D) of baricitinib. The initial dose is 2 mg once daily, and the maximum dose is 4 mg once daily. Additional patients may be enrolled to further explore a selected dose defined by dose escalation cohorts (up to 9 patients in each dose level).

Phase 2 part:

The phase 2 part is a single-arm, open-label study to assess the efficacy and safety of baricitinib at RP2D in patients with thrombopoietin-receptor-agonist-refractory persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation. Patients in phase 1b who were treated with baricitinib at the RP2D will be included in the phase 2 efficacy endpoint analyses.

Inclusion Criteria:

• Aged 18-70 years;
• Underwent allo-HSCT;
• Meet the diagnostic criteria for delayed platelet engraftment (DPE) or secondary failure of platelet recovery (SFPR);
• Have platelet counts consistently <20 ×10^9/L or transfusion-dependent within 14 days prior to enrollment;
• Have received adequate corticosteroid and TPO-RA therapy for persistent thrombocytopenia for no less than 4 weeks, with treatment failure or intolerance;
• Complete donor chimerism.

Exclusion Criteria:

• Relapse of hematologic malignancy or MRD positivity;
• Active infection;
• Active graft-versus-host disease;
• Thrombotic microangiopathy;
• Primary graft failure or poor graft function;
• Presence of other factors that may lead to secondary thrombocytopenia at the time of PT diagnosis;
• History of systemic herpes zoster infection within 12 weeks prior to enrollment screening;
• Acute or chronic infection with HBV, HCV, or HIV;
• Evidence of active tuberculosis, or history of active tuberculosis without documented standard anti-tuberculosis treatment, or close contact with active tuberculosis without documented standard tuberculosis prophylaxis;
• Receipt of a live vaccine within 12 weeks prior to enrollment screening, or planned receipt of a live vaccine during the study period;
• Clinically significant thromboembolic event within 24 weeks prior to enrollment screening, or current use of anticoagulant medications deemed by the investigator to carry an uncontrollable risk;
• Estimated glomerular filtration rate <50 mL/min/1.73 m^2;
• Severe pre-existing or current conditions involving the cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, nervous, or neuropsychiatric systems, or other severe or unstable illnesses or laboratory abnormalities that will make the study drug unacceptable for the patient or can interfere study data;
• Participation in another clinical trial within 30 days prior to enrollment.