The Use of Eltrombopag Post HSCT in BMFS

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05466201

Collaborator

(none)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Bone marrow failure disease(BMFD) is a kind of bone marrow due to congenital or acquired hematopoietic stem cells (hemopoietic stem cell, HSC) function damage. Allogenic hemopoietic stem cell transplantation (Allo-HSCT) might be the most possible treatment to cure the disease.However, 5-26% of patients have been reported to have delayed platelet engraftment (DPE), which is defined as persistent severe thrombocytopenia (<20 × 109/L) for >35 days after transplantation . To date, no standard treatment and prevention has been recommended for DPE. In patients with DPE, the amount of transfusion, the increased risk of infection, and the prolonged average hospital stay were independent risk factors affecting the prognosis of allo-HSCT patients. Due to continuous and progressive failure in the bone marrow hematopoiesis, thrombocytopenia post HSCT is more common in BMFD patients and often achieves low response to conventional therapy, such as platelet transfusion. Therefore, it is of great significance to effectively promote hematopoietic reconstruction to improve the prognosis of transplant patients.

Condition or Disease	Intervention/Treatment	Phase
Stem Cell Transplant Complications	Drug: Eltrombopag 25 MG Oral Tablet Drug: Thrombopoietin	Phase 2/Phase 3

Detailed Description

Bone marrow failure disease(BMFD) is a kind of bone marrow due to congenital or acquired hematopoietic stem cells (hemopoietic stem cell, HSC) function damage. Generally, BMFD can be divided into two categories based on pathogenesis, which is primary and secondary BMFD. The latter is commonly seen secondary to infection, cancer, drugs, while aplastic anemia(AA), myelodysplastic syndromes(MDS), paroxysmal nocturnal haemoglobinuria(PNH) and Fanconi anaemia(FA) are included in primary BMFD. Although immunotherapy or allogenic hemopoietic stem cell transplantation (Allo-HSCT) can be selected based on different individuals, allo-HSCT is still the most effective treatment for diseases that pose a greater threat to life or have a higher degree of malignancy, such as sereve aplastic anemia(SAA), MDS and PNH. Patients undergoing allo-HSCT typically achieve neutrophil and megakaryocyte reconstruction within 2 weeks and 3 weeks after transplantation respectively. However, 5-26% of patients have been reported to have delayed platelet engraftment (DPE), which is defined as persistent severe thrombocytopenia (<20 × 109/L) for >35 days after transplantation . To date, no standard treatment and prevention has been recommended for DPE. In patients with DPE, the amount of transfusion, the increased risk of infection, and the prolonged average hospital stay were independent risk factors affecting the prognosis of allo-HSCT patients. Due to continuous and progressive failure in the bone marrow hematopoiesis, thrombocytopenia post HSCT is more common in BMFD patients and often achieves low response to conventional therapy, such as platelet transfusion. Therefore, it is of great significance to effectively promote hematopoietic reconstruction to improve the prognosis of transplant patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Multicenter Clinical Study of a TPO Receptor Agonist (Eltrombopag) in the Acceleration of Engraftment Post Hematopoietic Stem Cell Transplantation of Bone Marrow Failure Diseases

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jul 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Other: rhTPO group recombinant human thrombopoietin (rhTPO) will be administrated at the dose of 300U/d subcutaneously from the 4th day to 17th day post hematopoietic stem cell transplantation.	Drug: Thrombopoietin rhTPO has been proved to be effective and safe for patients post HSCT, so we use it as control group. Other Names: rhTPO
Experimental: Eltrombopag group Eltrombopag treatment will be started at the dose of 50mg/d from the 4th day post hematopoietic stem cell transplantation, and the dose will be titrated by 25mg each every 7 days up to 100mg/d according to the tolerability. If not tolerable, reduce the dose to the previous tolerable level (if not tolerable at 50mg/d, reduce to 25mg/d) and maintain this dose for the following 7 days, with the attempt to restart dose escalation after this 7-day period.	Drug: Eltrombopag 25 MG Oral Tablet Since thrombopoietin receptor agonists (TPO-RAs) have never been regularly used for promotion of cell engraftment post hematopoietic stem cell transplantation HSCT), we design this eltrombopag intervention to evaluate the safety and efficacy of TPO-RAs post HSCT. Other Names: TPO-RA

Arm

Intervention/Treatment

Other: rhTPO group

recombinant human thrombopoietin (rhTPO) will be administrated at the dose of 300U/d subcutaneously from the 4th day to 17th day post hematopoietic stem cell transplantation.

Drug: Thrombopoietin

rhTPO has been proved to be effective and safe for patients post HSCT, so we use it as control group.

Other Names:

rhTPO

Experimental: Eltrombopag group

Eltrombopag treatment will be started at the dose of 50mg/d from the 4th day post hematopoietic stem cell transplantation, and the dose will be titrated by 25mg each every 7 days up to 100mg/d according to the tolerability. If not tolerable, reduce the dose to the previous tolerable level (if not tolerable at 50mg/d, reduce to 25mg/d) and maintain this dose for the following 7 days, with the attempt to restart dose escalation after this 7-day period.

Drug: Eltrombopag 25 MG Oral Tablet

Since thrombopoietin receptor agonists (TPO-RAs) have never been regularly used for promotion of cell engraftment post hematopoietic stem cell transplantation HSCT), we design this eltrombopag intervention to evaluate the safety and efficacy of TPO-RAs post HSCT.

Other Names:

TPO-RA

Outcome Measures

Primary Outcome Measures

Number and proportion of platelet engraftment on day 35 post HSCT. [From day 28 to 35 post HSCT]
Platelet engraftment is defined as platelet count >20×109/L in consecutive 7 days (namely day 28 to day 35 after HSCT) without platelet transfusion in the prior 7 days (in other words, no platelet transfusion after day 21).

Secondary Outcome Measures

Number and proportion of subjects achieving neutrophil engraftment at day 35 post HSCT. [From day 28 to 35 post HSCT]
Neutrophil engraftment is defined as ANC>0.5×109/L for consecutive 3 days without administration of G-csf
Hematopoietic reconstruction time. [From day 1 to day 180 post HSCT]
Reconstruction time is defined as the time from day 1 after allo-HSCT to platelet or neutrophil engraftment
Overall survival (OS) [From day 1 to day 720 post HSCT or the time of the patients enrolled dead or quitting]
OS is defined as the time from the date of day 1 post HSCT to the date of death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients diagnosed as bone marrow failure disease who received allo-HSCT; Physical strength score 0-3 according to WHO standard

Exclusion Criteria:

single or double umbilical cord blood transplantation;
allergic to any of the research drugs involved in the protocol;
simultaneously suffering from another malignant tumor;
pregnant or lactating women;
participating in other clinical researchers at the same time;
patients with at least one following high risk factors of thrombosis: past medical history of thromboembolism, concurrent grade 2 to 3 hypertension (systolic BP>=160mmHg or diastolic BP>=100mmHg) , diabetes, obesity(BMI>30), family history of stroke, smoke for more than 10 years , or history of catheter thrombosis;
severe cataract;
Severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis, viral infection, active hepatitis B/C; for positive HBsAg and HBcAg, patient is excluded if hepatitis B DNA nucleic acid test is positive, DNA negative patients can enter this clinical trial; patients with hepatitis C who have a positive hepatitis C RNA nucleic acid test are excluded).;
Abnormal liver and kidney function: creatinine level ≥177 μmol/l (1.5mg/dl), transaminase and bilirubin levels increased significantly (3 times or more than the upper limit of normal), and who cannot be enrolled at the discretion of clinician.
In moribund condition or concurrent severe liver, kidney, heart, nerve, lung, infectious or metabolic diseases, the severity of which will cause the patient to be unable to tolerate the treatment regimen, or may die within 7-10 days