Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia After Haplo-HSCT

Peking University

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Thrombocytopenia; Stem Cell Transplant Complications

Treatments: Drug: Placebo; Drug: avatrombopag

Study type: Interventional

Funder types: Other

Identifiers

NCT06202625

2023PHD009-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 142 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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142 participants in 2 patient groups, including a placebo group

avatrombopag

Experimental group

Description:

Avatrombopag 20 mg/d will be taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to +D60 after haplo-HSCT. Routine treatment is allowed. Adjustment indication: When PLT<50×10^9/L or PLT transfusion dependent on the +D30 after haplo-HSCT, increase the dosage to 40 mg/d; When the dosage has been increased to 40 mg/d, and PLT≥80×10^9/L excluding the factor of PLT transfusion, decrease the dosage to 20 mg/d; When PLT≥80×10^9/L for 7 consecutive days excluding the factor of PLT transfusion, or PLT≥300×10^9/L excluding the factor of PLT transfusion, stop administration; When PLT<50×10^9/L or become PLT transfusion dependent after stopping administration, initiate administration again at the dosage 40 mg/d. PLT transfusion Indication: When PLT<20×10^9/L, and/or with the symptom or risk of bleeding.

Treatment:

Drug: avatrombopag

Placebo

Placebo Comparator group

Description:

Placebo 20 mg/d will be taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to +D60 after haplo-HSCT. Routine treatment is allowed. Adjustment indication: When PLT<50×10^9/L or PLT transfusion dependent on the +D30 after haplo-HSCT, increase the dosage to 40 mg/d; When the dosage has been increased to 40 mg/d, and PLT≥80×10^9/L excluding the factor of PLT transfusion, decrease the dosage to 20 mg/d; When PLT≥80×10^9/L for 7 consecutive days excluding the factor of PLT transfusion, or PLT≥300×10^9/L excluding the factor of PLT transfusion, stop administration; When PLT<50×10^9/L or become PLT transfusion dependent after stopping administration, initiate administration again at the dosage 40 mg/d. PLT transfusion Indication: When PLT<20×10^9/L, and/or with the symptom or risk of bleeding.

Treatment:

Drug: Placebo