Clinical trial NCT06202625: Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia After Haplo-HSCT
Official title: Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia After Haploidentical Hematopoietic Stem Cell Transplantation: Prospective, Multi-center, Double-blinded, Randomized Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Thrombocytopenia
Stem Cell Transplant Complications
Keywords: Thrombocytopenia
hematopoietic stem cell transplantation
haploidentical
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Xiangya Hospital of Central South University
name: Sichuan Provincial People's Hospital
name: First Affiliated Hospital of Harbin Medical University
name: The First Affiliated Hospital of Zhengzhou University
name: First Affiliated Hospital of Xinjiang Medical University
name: Shanxi Bethune Hospital
name: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Tang-Du Hospital
name: The First Affiliated Hospital of Nanchang University
First posted: 2024-01-11
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: the proportion of complete response(CR) on day 60 after haplo-HSCT
timeFrame: from randomization to day 60 after haplo-HSCT
Secondary outcomes:
measure: the proportion of resonse(R)/remission on day 60 after haplo-HSCT
timeFrame: from randomization to day 60 after haplo-HSCT
measure: the proportion of R/CR on day 30 after haplo-HSCT
timeFrame: from randomization to day 30 after haplo-HSCT
measure: the proportion of CR/remission on day 90 after haplo-HSCT
timeFrame: from randomization to day 90 after haplo-HSCT
measure: Time to R/CR/remission
timeFrame: from randomization to day 60 after haplo-HSCT
measure: PLT transfusion dependence
timeFrame: from randomization to day 60 after haplo-HSCT
measure: neutrophil engraftment
timeFrame: from randomization to day 30 after haplo-HSCT
measure: GVHD
timeFrame: from randomization to 1 year after haplo-HSCT
measure: overall survival(OS)
timeFrame: from randomization to 1 year after haplo-HSCT
measure: disease free survival(DFS)
timeFrame: from randomization to 1 year after haplo-HSCT
measure: non-relapse mortality(NRM)
timeFrame: from randomization to 1 year after haplo-HSCT
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital, School of Medicine, South China University of Technology
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Harbin
country: China
facility: The First Affiliated Hospital, Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Taiyuan
country: China
facility: Shanxi Tumor Hospital Affiliated to Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: Tangdu Hospital, PLA Air Force Military Medical University
state: Shanxi
city: Chongqing
country: China
facility: Xinqiao Hospital, Army Military Medical University
state: Sichuan
city: Kunming
country: China
facility: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
state: Yunnan
city: Tianjin
country: China
facility: Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
affiliation: Peking University People's Hospital
name: Xiaohui Zhang
role: PRINCIPAL_INVESTIGATOR
References: