Baricitinib for Post-HSCT Persistent Thrombocytopenia (BAPT)
Safety and Efficacy of Baricitinib in Thrombopoietin-Receptor-Agonist-Refractory Persistent Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplantation: A Phase Ib/II Study
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
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.
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Peng Zhao
- Phone Number: +86-18810323668
- Email: zpeng702@163.com
Study Locations
-
-
Beijing Municipality
-
Beijing, Beijing Municipality, China, 100044
- Peking University People's Hospital
-
Contact:
- Yue Jin
- Phone Number: +86-18161502996
- Email: jinyue@pku.edu.cn
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Baricitinib
Group A: Open label baricitinib at 2 mg daily (Phase 1) Group B: Open label baricitinib at 4 mg daily (Phase 1) Group C: Open label baricitinib at the RP2D (Phase 2)
|
Baricitinib, an orally administered, selective, reversible JAK1/2 inhibitor.
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Adverse events in the Ib part
Time Frame: 24 weeks
|
The incidence and severity of adverse events are assessed using the criteria of CTCAE 5.0.
|
24 weeks
|
|
Overall response rate (ORR) for the IIa part
Time Frame: 12 weeks
|
The proportion of patients achieving an overall response (OR), defined as a platelet count ≥20×10^9/L maintained for more than 7 days without transfusion support.
Platelet counts obtained within 4 weeks after rescue therapy were not included in the efficacy assessment.
|
12 weeks
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall response rate (ORR) for the Ib part
Time Frame: 12 weeks
|
The proportion of patients achieving an overall response (OR), defined as a platelet count ≥20×10^9/L maintained for more than 7 days without transfusion support.
Platelet counts obtained within 4 weeks after rescue therapy were not included in the efficacy assessment.
|
12 weeks
|
|
Complete response (CR)
Time Frame: 12 weeks
|
The proportion of patients achieving a complete response (CR), defined as a platelet count ≥50×10^9/L maintained for more than 7 days without transfusion support.
Platelet counts obtained within 4 weeks after rescue therapy were not included in the efficacy assessment.
|
12 weeks
|
|
Durable response
Time Frame: 24 weeks
|
The proportion of patients achieving a durable response (DR), defined as a platelet count ≥20×10^9/L maintained for more than 8 weeks without transfusion.
Platelet counts obtained within 4 weeks after rescue therapy were not included in the efficacy assessment.
|
24 weeks
|
|
Time to response
Time Frame: 12 weeks
|
The time from the date of the first dose of baricitinib to the date of OR or CR.
|
12 weeks
|
|
Bleeding events
Time Frame: 24 weeks
|
Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale: 0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss.
|
24 weeks
|
|
Rescue medication
Time Frame: 24 weeks
|
Time and type of rescue medications, defined as any additional treatment intended to prevent bleeding or raise the platelet counts, including a dose increase of more than 10% above baseline of the concomitant medication and any additional PT-modifying agents (e.g., corticosteroids, intravenous immunoglobulin, and platelet transfusions).
|
24 weeks
|
|
Adverse events in the IIa part
Time Frame: 24 weeks
|
Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
|
24 weeks
|
|
Overall Survival (OS)
Time Frame: 104 weeks
|
The overall survival of patients who received at least one dose of baricitinib in the study.
|
104 weeks
|
|
Transplantation-related mortality (TRM)
Time Frame: 104 weeks
|
All deaths without relapse or disease progression occurring after transplantation as a direct or indirect consequence of the transplant procedure or associated complications in patients who received at least one dose of baricitinib in the study.
|
104 weeks
|
|
Relapse or progression of underlying disease
Time Frame: 104 weeks
|
Relapse or progression of underlying disease of patients who received at least one dose of baricitinib in the study.
|
104 weeks
|
|
Graft-versus-host disease
Time Frame: 104 weeks
|
The incidence and severity of acute graft-versus-host disease and chronic graft-versus-host disease in patients who received at least one dose of baricitinib in the study.
|
104 weeks
|
Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- 2026PHD005-BAPT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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