A Randomized Phase II Study of Romiplostim vs. rhTPO for Platelet Engraftment After Allo-HSCT in Patients With MDS and Aplastic Anemia (PROMPT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Rate of Platelet Engraftment by Day +60 (Platelets ≥50×10^9/L without transfusion for 7 consecutive days)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •Persistent platelet count <20×10⁹/L with platelet transfusion dependence between post-transplant days +4 and +
- •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.
排除标准
- •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.
研究组 & 干预措施
Romiplostim
Participants will receive subcutaneous Romiplostim injections at a starting dose of 5.0 µg/kg once weekly, beginning on transplant day +4. The dose will be adjusted weekly based on platelet counts. Treatment continues until the platelet count is ≥50×10⁹/L without transfusion for 7 days, until day +60 post-transplant, or for a maximum of 8 weeks, whichever occurs first.
干预措施: Romiplostim (Drug)
rhTPO (Recombinant Human Thrombopoietin)
Participants will receive subcutaneous rhTPO injections at a fixed dose of 15000 U once daily, beginning on transplant day +4. Treatment continues until the platelet count is ≥50×10⁹/L without transfusion for 7 days, until day +60 post-transplant, or for a maximum of 8 weeks, whichever occurs first.
干预措施: Recombinant Human Thrombopoietin (Drug)
结局指标
主要结局
Rate of Platelet Engraftment by Day +60 (Platelets ≥50×10^9/L without transfusion for 7 consecutive days)
时间窗: From the start of transplantation until Day 60 post-transplant (or until the engraftment criterion is met).
To preliminarily evaluate and compare the efficacy of romiplostim versus rhTPO in promoting platelet recovery after allo-HSCT. Engraftment is defined as achieving a platelet count ≥50×10\^9/L without transfusion support for 7 consecutive days.
Incidence of ≥ Grade 3 Adverse Events within 100 Days Post-Transplant (including GVHD and thrombotic events)
时间窗: From the start of transplantation until Day 100 post-transplant.
To assess and compare the safety profile between romiplostim and rhTPO, focusing on severe adverse events. Events of special interest include acute/chronic GVHD (graded per NIH criteria) and thrombotic events (e.g., TA-TMA, deep vein thrombosis).
次要结局
- 60-Day Platelet Engraftment Rate(At Day 60 post-transplant.)
- Platelet Transfusion Requirements (Days 0-60)(From Day 0 (day of transplant) to Day 60 post-transplant.)
- Overall Survival (OS)(From date of transplant until death from any cause, assessed up to 2 years.)
- Progression-Free Survival (PFS)(From date of transplant until disease progression/relapse or death from any cause, assessed up to 2 years.)
- Non-Relapse Mortality (NRM)(From date of transplant until death from non-relapse causes, assessed up to 2 years.)