Allogeneic Hematopoietic Stem Cell Transplantation, Persistent Thrombocytopenia
Conditions
Keywords
Persistent thrombocytopenia, Allogeneic Hematopoietic Stem Cell Transplantation, Baricitinib
Brief summary
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.
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.
Interventions
DRUGBaricitinib
Baricitinib, an orally administered, selective, reversible JAK1/2 inhibitor.
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events in the Ib part | 24 weeks | The incidence and severity of adverse events are assessed using the criteria of CTCAE 5.0. |
| Overall response rate (ORR) for the IIa part | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) for the Ib part | 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. |
| Complete response (CR) | 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. |
| Durable response | 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. |
| Time to response | 12 weeks | The time from the date of the first dose of baricitinib to the date of OR or CR. |
| Bleeding events | 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. |
| Rescue medication | 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). |
| Adverse events in the IIa part | 24 weeks | Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
| Overall Survival (OS) | 104 weeks | The overall survival of patients who received at least one dose of baricitinib in the study. |
| Transplantation-related mortality (TRM) | 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. |
| Relapse or progression of underlying disease | 104 weeks | Relapse or progression of underlying disease of patients who received at least one dose of baricitinib in the study. |
| Graft-versus-host disease | 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. |
Countries
China
Contacts
CONTACTPeng Zhao
Outcome results
None listed