Overview
This study is for adults aged 18-65 with myelodysplastic syndrome (MDS) or severe aplastic anemia (AA) who are scheduled to receive a donor stem cell transplant (allogeneic hematopoietic stem cell transplant). After the transplant, it is critical for the body to start making its own blood cells again. A common and serious problem is a delay in the recovery of platelets (the cells that help stop bleeding), which increases the risk of bleeding, infection, and death.
This study aims to see if a new treatment can help platelets recover faster and more safely after transplant. We are comparing two drugs:
Romiplostim: A long-acting injection given just once a week. rhTPO (Recombinant Human Thrombopoietin): A standard injection given every day. Both drugs are designed to help the body make more platelets. The main question is whether the once-weekly romiplostim works as well or better than the daily rhTPO, and if it is safe.
About 66 patients will participate. By random chance (like flipping a coin), each participant will be assigned to receive either romiplostim or rhTPO. The treatment will start a few days after the transplant and continue until platelets recover to a safe level or for up to 8 weeks. Doctors will closely monitor all participants for 100 days to track platelet recovery, need for transfusions, side effects, and overall health.
Description
This is a prospective, single-center, randomized, open-label, parallel-controlled Phase II clinical trial. The primary objective is to provide a preliminary efficacy estimate and evaluate the safety of romiplostim compared to recombinant human thrombopoietin (rhTPO) for promoting platelet engraftment following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome (MDS) or aplastic anemia (AA).
Study Design and Population:
The study will enroll approximately 74 patients to achieve 66 evaluable subjects, randomized in a 1:1 ratio to the romiplostim group or the rhTPO group. Randomization will be stratified by the underlying disease (MDS vs. AA). Eligible patients are aged 18-65 years, diagnosed with MDS or severe/very severe AA (SAA/VSAA), and are candidates for allo-HSCT from a matched sibling, haploidentical, or unrelated donor (including cord blood). Key inclusion criteria require a platelet count \<20×10⁹/L with transfusion dependence between day +4 and day +10 post-transplant. Major exclusion criteria include uncontrolled active infection, significant history of thrombosis, active transplant-associated thrombotic microangiopathy (TA-TMA), pre-transplant bone marrow fibrosis ≥ MF-2 grade, and known allergy to the study drugs.
- Interventions
Experimental Group (n≈33): Romiplostim administered subcutaneously at a starting dose of 5.0 µg/kg once weekly, beginning on transplant day +4. Subsequent doses (from day +18) will be adjusted weekly based on platelet counts.
Active Control Group (n≈33): rhTPO administered subcutaneously at a fixed dose of 15000 U once daily, beginning on transplant day +4.
Treatment for both groups continues until the platelet count is ≥50×10⁹/L without transfusion support for 7 consecutive days, until day +60 post-transplant, or for a maximum of 8 weeks, whichever occurs first. All patients will receive standardized transplant supportive care.
- Endpoints
Primary Endpoints:
Platelet engraftment time, defined as the first of three consecutive days with a platelet count ≥20×10⁹/L without platelet transfusion in the preceding 7 days.
Incidence of ≥ Grade 3 adverse events (AEs) within 100 days post-transplant, with specific focus on graft-versus-host disease (GVHD) and thrombotic events.
Secondary Endpoints: Platelet engraftment rate at day 60 (≥50×10⁹/L), total platelet transfusion units from day 0 to 60, overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM).
Exploratory Endpoints: Immune reconstitution (lymphocyte subsets), megakaryocyte-related biomarkers, and a pharmacoeconomic evaluation.
Oversight and Safety:
An Independent Data Safety Monitoring Committee (DSMB) will be established to periodically review accumulated safety data. Safety will be actively monitored through weekly clinical and laboratory assessments during the treatment period, with specific focus on thrombotic events, GVHD, and potential clonal evolution. The study will be conducted at the Department of Hematology, The First Affiliated Hospital of Soochow University, China, following approval by its institutional Ethics Committee.
Eligibility
Inclusion Criteria:
- Age 18-65 years (inclusive).
- Diagnosis of Myelodysplastic Syndrome (MDS) per WHO criteria, or Severe/Very Severe Aplastic Anemia (SAA/VSAA) per Camitta criteria, and deemed eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- Planned to receive allo-HSCT from a matched sibling, haploidentical, or unrelated donor (including cord blood).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Persistent platelet count \<20×10⁹/L with platelet transfusion dependence between post-transplant days +4 and +10. Transfusion dependence is defined as platelet count not doubling within 24-48 hours after transfusion or ongoing need for prophylactic transfusion.
- Adequate cardiac, hepatic, and renal function as required for transplantation, per investigator assessment.
- Voluntary participation with written informed consent obtained prior to any study-specific procedures.
Exclusion Criteria:
- Active, uncontrolled bacterial, fungal, or viral infection at the time of enrollment.
- History of arterial thrombosis, or venous thromboembolism within the past 6 months (unless cured or stable for over 6 months).
- Active transplant-associated thrombotic microangiopathy (TA-TMA).
- Pre-transplant bone marrow biopsy showing fibrosis grade ≥ MF-2 (according to WHO criteria).
- Known hypersensitivity to Romiplostim, recombinant human thrombopoietin (rhTPO), or any of their excipients.
- Pregnant or lactating women.
- Women of childbearing potential or men with partners of childbearing potential who are unwilling to use highly effective contraception during the study period and for at least 3 months after the last dose of study drug.
- Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study.
