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The Use of Eltrombopag Post HSCT in BMFS

Primary Purpose

Stem Cell Transplant Complications

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Eltrombopag 25 MG Oral Tablet

Supportive care

About this trial

This is an interventional prevention trial for Stem Cell Transplant Complications focused on measuring Hematopoietic stem cell transplantation, Bone marrow failure syndrome, Eltrombopag, Thrombocytopenia

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

supportive care

Eltrombopag group

Arm Description

patients in this group will receive supportive care, including blood products transfusion, anti-infective therapy rather than rhTPO or TPO-RAs.

Eltrombopag treatment will be started at the dose of 50mg/d from the 1st 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.

Outcomes

Primary Outcome Measures

Number and proportion of platelet engraftment on day 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.

Neutrophil engraftment is defined as ANC>0.5×109/L for consecutive 3 days without administration of G-csf

Hematopoietic reconstruction time.

Reconstruction time is defined as the time from day 1 after allo-HSCT to platelet or neutrophil engraftment

Overall survival (OS)

OS is defined as the time from the date of day 1 post HSCT to the date of death due to any cause.

Full Information

NCT ID

NCT05466201

First Posted

July 12, 2022

Last Updated

December 11, 2022

Sponsor

The First Affiliated Hospital of Soochow University

1. Study Identification

Unique Protocol Identification Number

NCT05466201

Brief Title

The Use of Eltrombopag Post HSCT in BMFS

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 22, 2022 (Actual)

Primary Completion Date

July 31, 2025 (Anticipated)

Study Completion Date

July 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The First Affiliated Hospital of Soochow University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stem Cell Transplant Complications

Keywords

Hematopoietic stem cell transplantation, Bone marrow failure syndrome, Eltrombopag, Thrombocytopenia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

supportive care

Arm Type

Other

Arm Description

patients in this group will receive supportive care, including blood products transfusion, anti-infective therapy rather than rhTPO or TPO-RAs.

Arm Title

Eltrombopag group

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Eltrombopag 25 MG Oral Tablet

Other Intervention Name(s)

TPO-RA

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Supportive care

Other Intervention Name(s)

support

Intervention Description

Patients receive transfusion of blood products, including platelets and red blood cells.

Primary Outcome Measure Information:

Title

Number and proportion of platelet engraftment on day 35 post HSCT.

Description

Time Frame

From day 28 to 35 post HSCT

Secondary Outcome Measure Information:

Title

Number and proportion of subjects achieving neutrophil engraftment at day 35 post HSCT.

Description

Neutrophil engraftment is defined as ANC>0.5×109/L for consecutive 3 days without administration of G-csf

Time Frame

From day 28 to 35 post HSCT

Title

Hematopoietic reconstruction time.

Description

Reconstruction time is defined as the time from day 1 after allo-HSCT to platelet or neutrophil engraftment

Time Frame

From day 1 to day 180 post HSCT

Title

Overall survival (OS)

Description

OS is defined as the time from the date of day 1 post HSCT to the date of death due to any cause.

Time Frame

From day 1 to day 720 post HSCT or the time of the patients enrolled dead or quitting

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Meng Zhou, MD

Phone

+86

zhoumeng@suda.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Yue Han, PhD,MD

Phone

+8615606133001

hanyue@suda.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Depei Wu, PhD,MD

Organizational Affiliation

The First Affiliated Hospital of Soochow University

Official's Role

Study Chair

Facility Information:

Facility Name

The First Affiliated Hospital of Soochow University

City

Suzhou

State/Province

Jiangsu

ZIP/Postal Code

215006

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yue Han, professor

Phone

+86 13901551669

hanyuesz@163.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

10707996

Citation

Nash RA, Kurzrock R, DiPersio J, Vose J, Linker C, Maharaj D, Nademanee AP, Negrin R, Nimer S, Shulman H, Ashby M, Jones D, Appelbaum FR, Champlin R. A phase I trial of recombinant human thrombopoietin in patients with delayed platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2000;6(1):25-34. doi: 10.1016/s1083-8791(00)70049-8.

Results Reference

background

PubMed Identifier

30679824

Citation

Marotta S, Marano L, Ricci P, Cacace F, Frieri C, Simeone L, Trastulli F, Vitiello S, Cardano F, Pane F, Risitano AM. Eltrombopag for post-transplant cytopenias due to poor graft function. Bone Marrow Transplant. 2019 Aug;54(8):1346-1353. doi: 10.1038/s41409-019-0442-3. Epub 2019 Jan 24.

Results Reference

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PubMed Identifier

31830528

Citation

Mahat U, Rotz SJ, Hanna R. Use of Thrombopoietin Receptor Agonists in Prolonged Thrombocytopenia after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2020 Mar;26(3):e65-e73. doi: 10.1016/j.bbmt.2019.12.003. Epub 2019 Dec 9.

Results Reference

background

PubMed Identifier

27923195

Citation

Zeidan AM, Battiwalla M, Berlyne D, Winkler T. Aplastic Anemia and MDS International Foundation (AAMDSIF): Bone marrow failure disease scientific symposium 2016. Leuk Res. 2017 Feb;53:8-12. doi: 10.1016/j.leukres.2016.11.011. Epub 2016 Nov 24.

Results Reference

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PubMed Identifier

11167808

Citation

Dominietto A, Raiola AM, van Lint MT, Lamparelli T, Gualandi F, Berisso G, Bregante S, Frassoni F, Casarino L, Verdiani S, Bacigalupo A. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol. 2001 Jan;112(1):219-27. doi: 10.1046/j.1365-2141.2001.02468.x.

Results Reference

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The Use of Eltrombopag Post HSCT in BMFS

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