Stem Cell Transplant Complications, Thrombocytopenia
Conditions
Keywords
Thrombocytopenia, hematopoietic stem cell transplantation, haploidentical
Brief summary
In this study, investigators aim to evaluate the efficacy of avatrombopag in thrombocytopenic patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) through a prospective, multi-center, double-blinded, randomized placebo-controlled clinical trial.
Detailed description
Thrombocytopenia is a common and severe complication after haplo-HSCT, including primary isolated thrombocytopenia (PIT) and secondary failure of platelet recovery (SFPR), which may cause bleeding and infection, and thus influence the OS, DFS, and NRM of the patients. Avatrombopag has been proved effective and safe in patients with chronic liver disease(CLD) and immune thrombocytopenia (ITP) and have been approved for CLD-associated thrombocytopenia undergoing elective invasive procedure (FDA&NMPA) and ITP(FDA). Chinese consensus has recommended avatrombopag and some other thrombopoietin receptor agonists (TPO-RAs) to treat thrombocytopenia after haplo-HSCT. However, it lacks prospective studies to support that.Investigators aim to evaluate the efficacy of avatrombopag in thrombocytopenic patients after haplo-HSCT through a prospective, multi-center, double-blinded, randomized placebo-controlled clinical trial. The patients with PLT\<20×10\^9/L or transfusion dependent on the 7th day (+D7) after haplo-HSCT are included and assigned in a 1:1 randomization schedule to the avatrombopag group (receiving avatrombopag, n=71）and the placebo group (receiving placebo, n=71). The primary endpoint is the proportion of participants whose PLT≥50×10\^9/L on +D60 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above. Second endpoints includ the proportion of participants whose PLT≥100×10\^9/L on +D60 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above, the proportion of participants whose PLT≥20×10\^9/L and whose PLT≥50×10\^9/L on +D30 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above, the proportion of participants whose PLT≥50×10\^9/L and whose PLT≥100×10\^9/L on +D90 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above, the first day to achieve PLT≥20×10\^9/L and PLT≥50×10\^9/L and PLT≥100×10\^9/L without the need for PLT transfusion for consecutive 7 days and above within +D60 after haplo-HSCT, the percentage of participants who need PLT transfusion and the average count of PLT from +D7 to + D60 after haplo-HSCT, the first day and the percentage of participants to achieve absolute neutrophil≥500/μL for consecutive 3 days within +D30 after haplo-HSCT, the graft-versus-host disease(GVHD), infection, the overall survival(OS),the disease free survival(DFS) and the non-relapse mortality(NRM) rates of participants within the first year after haplo-HSCT.
Interventions
DRUGavatrombopag
The avatrombopag 20mg/d will be orally taken from +D7 after haplo-HSCT until meeting the adjustment indication or to +D60 after haplo-HSCT; When PLT\<50×10\^9/L or PLT transfusion-dependent on the +D30 after haplo-HSCT, increase avatrombopag dosage to 40 mg/d; When PLT≥80×10\^9/L and without PLT transfusion within avatrombopag dosage at 40 mg/d, decrease avatrombopag dosage to 20 mg/d; When PLT≥80×10\^9/L for 7 consecutive days or PLT≥300×10\^9/L and without PLT transfusion, stop avatrombopag; When PLT\<50×10\^9/L or PLT transfusion-dependent after stopping avatrombopag , reuse avatrombopag at 40 mg/d.
DRUGPlacebo
The placebo 20mg/d will be orally taken from +D7 after haplo-HSCT until meeting the adjustment indication or to +D60 after haplo-HSCT; When PLT\<50×10\^9/L or PLT transfusion-dependent on the +D30 after haplo-HSCT, increase placebo dosage to 40 mg/d; When PLT≥80×10\^9/L and without PLT transfusion within placebo dosage at 40 mg/d, decrease placebo dosage to 20 mg/d; When PLT≥80×10\^9/L for 7 consecutive days or PLT≥300×10\^9/L and without PLT transfusion, stop placebo; When PLT\<50×10\^9/L or PLT transfusion-dependent after stopping placebo, reuse placebo at 40 mg/d.
Sponsors
Xiangya Hospital of Central South University
Sichuan Provincial People's Hospital
First Affiliated Hospital of Harbin Medical University
The First Affiliated Hospital of Zhengzhou University
First Affiliated Hospital of Xinjiang Medical University
Shanxi Bethune Hospital
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Tang-Du Hospital
The First Affiliated Hospital of Nanchang University
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged between 18-65 years; 2. PLT\<20×10\^9/L or transfusion dependent on +D7 after haplo-HSCT; 3. Agree to receive the treatment of avatrombopag after Haplo-HSCT and sign the informed consent form.
Exclusion criteria
1. With active infection; 2. ALT or AST\>3ULN, or total Bil\>2ULN 3. Ccr\<50 mL/min; 4. With the history of arteriovenous thrombosis; 5. With history of cardiovascular disease (such as NYHA Class III/IV congestive heart failure, arrhythmia that increases the risk of thromboembolic events \[such as atrial fibrillation\] and angina), and subjects who have undergone coronary stent implantation, angioplasty, or coronary artery bypass grafting; 6. With treatment of drugs to promote platelet production two weekes before enrollment, including but not limited to rhTPO and TPO-RA; 7. HBsAg or anti-HCV or anti-HIV positive; 8. Known to be allergic to avatrombopag and any of its excipients; 9. With secondary or multiple HSCT; 10. Females who were pregnant or breastfeeding or who had fertile ability but refuse to take effective contraceptive measures during and one month after this trial; 11. With any other clinical trial of investigational product or device within 30 days prior to the baseline visit, except for observational study; 12. Deemed unsuitable for enrollment by the investigator for any history of or concomitant medical condition. 13. Concomitant medication:The rhIL-11, rhTPO or TPO-RA(such as eltrombopag, hetrombopag and romiplostim) and desitabine, etc. were not allowed for use during this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the proportion of complete response(CR) on day 60 after haplo-HSCT | from randomization to day 60 after haplo-HSCT | the proportion of participants whose PLT≥50×10\^9/L on day 60 after haplo-HSCT independent of PLT transfusion for 7 consecutive days or above |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the proportion of R/CR on day 30 after haplo-HSCT | from randomization to day 30 after haplo-HSCT | the proportion of participants whose PLT≥20×10\^9/L or PLT≥50×10\^9/L on day 30 after haplo-HSCT independent of PLT transfusion for 7 consecutive days or above,respectively |
| the proportion of CR/remission on day 90 after haplo-HSCT | from randomization to day 90 after haplo-HSCT | the proportion of participants whose PLT≥50×10\^9/L or PLT≥100×10\^9/L on day 90 after haplo-HSCT independent of PLT transfusion for 7 consecutive days or above |
| Time to R/CR/remission | from randomization to day 60 after haplo-HSCT | the first day of the time to achieve PLT≥20×10\^9/L and PLT≥50×10\^9/L or PLT≥100×10\^9/L independent of PLT transfusion for consecutive 7 days and above within 60 days after haplo-HSCT,respectively |
| PLT transfusion dependence | from randomization to day 60 after haplo-HSCT | the percentage of participants who need PLT transfusion and the average volume of transfused PLT from day 7 to day 60 after haplo-HSCT |
| the proportion of resonse(R)/remission on day 60 after haplo-HSCT | from randomization to day 60 after haplo-HSCT | the proportion of participants whose PLT≥20×10\^9/L or PLT≥100×10\^9/L on day 60 after haplo-HSCT independent of PLT transfusion for 7 consecutive days or above |
| GVHD | from randomization to 1 year after haplo-HSCT | the incidece of graft versus host disease(GVHD) |
| overall survival(OS) | from randomization to 1 year after haplo-HSCT | the 1-year OS of participants |
| disease free survival(DFS) | from randomization to 1 year after haplo-HSCT | the 1-year DFS of participants |
| non-relapse mortality(NRM) | from randomization to 1 year after haplo-HSCT | the 1-year NRM of participants |
| neutrophil engraftment | from randomization to day 30 after haplo-HSCT | the first day and the percentage of participants to achieve absolute neutrophil≥500/μL for consecutive 3 days within 30 days after haplo-HSCT |
Countries
China
Contacts
Primary ContactHaixia Fu
Outcome results
None listed