Phase II Trial of Reduced Dose Post Transplant Cyclophosphamide After Haploidentical Hematopoietic Stem Cell Transplant in Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Severe (Grade 3-4) aGvHD
研究概览
简要总结
Cyclophosphamide is the name of a medicine given to prevent graft-versus-host-disease (GVHD) after half-matched transplant. This medicine is given on the 3rd and 4th day after stem cell transplant. The standard dose of this medicine is 50 mg per kg of the patient's weight given on the 3rd and the 4th day. However, using this medicine at this dose of 50 mg / kg for 2 days is associated with certain problems such as susceptibility to infections and delay in the recovery of the immune system after stem cell transplant. Therefore, several research groups across the world have tried to reduce the dose of cyclophosphamide that is used. These groups have tried reducing the dose from 50 mg per kg to 25-40 mg per kg. These studies have shown that the reduced dose cyclophosphamide is equally effective in preventing GVHD. However, these studies are carried out on small numbers of patients and further studies are essential to confirm whether reduced dose of cyclophosphamide is equally effective. In this study, we will use cyclophosphamide at a lower dose (25 mg/kg x 2 days) and see if the lower dose results in equal efficacy but lesser toxicities This is a single-arm study. All participants will receive the same treatment; there is no comparison group.
Participants will:
Adults (age ≥18) undergoing haploidentical stem cell transplant for blood cancers Receive low-dose cyclophosphamide (25 mg/kg/day) on Day 3 and Day 4 after transplant Also receive standard GVHD preventive medicines (calcineurin inhibitor and mycophenolate) Undergo regular blood tests, immune system monitoring, and GVHD assessments Have immune cell and cytokine profiles analyzed through blood samples
详细描述
Background: Allogeneic Hematopoietic stem cell transplant (HSCT) is often the only curative treatment option for patients with end stage hematological malignancies. Haploidentical HSCT is increasingly being adopted worldwide due to ease of access to donors. Post transplant cyclophosphamide (PTCy) has revolutionized the way the world does T cell replete haploidentical transplant. However, the success of PTCy comes at the cost of delayed engraftment and increased organ toxicities. Reduced dose of PTCy may be equally effective in GvHD prevention and translate into better engraftment kinetics and immune reconstitution Objectives: To evaluate the GvHD prophylactic effect of reduced dose PTCy in combination with Calcineurin inhibitors and MMF for haploidentical HSCT.
Novelty: The proposed study is a prospective phase 2 trial of reduced dose PTCy as GvHD prophylaxis in haplo HSCT. By demonstration of equal GvHD prevention efficacy of reduced dose PTCy this study would provide the base for phase 3 randomised trial and provide practice changing answers.
Study treatment:
Post-transplant Immunosuppression:
● GvHD prophylaxis regimen will consist of two doses of cyclophosphamide on D+3 and D+4 at 25mg/kg/day (that is half of the usual standard dose) with calcineurin inhibitor and mycophenolate mofetil / mycophenolate sodium. Mesna will be given with cyclophosphamide (this is standard of care). The use of calcineurin inhibitors and mycophenolate mofetil / mycophenolate sodium will be as per standard practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age ≥ 18 years
- •ECOG performance score of 0 or 1
排除标准
- •Presence of an active uncontrolled infection defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection.
- •Any medical or psychiatric illness which precludes the participant from giving informed consent.
- •Organ function criteria: Serious organ dysfunctions:
- •Serious cardiac dysfunction: Left ventricular ejection fraction < 45%; no uncontrolled arrhythmias or symptomatic cardiac disease.
- •Serious pulmonary organ dysfunction: Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =< 50% of predicted (corrected for haemoglobin).
- •Serious renal dysfunction: Measured serum creatinine clearance =< 60 mL/min.
- •Serious Hepatic dysfunction: Total serum bilirubin more than twice upper normal limit or Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3-fold higher than laboratory upper normal limits.
结局指标
主要结局
Severe (Grade 3-4) aGvHD
时间窗: at day 100 Post Transplant
To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD
次要结局
- Cumulative incidence of clinically significant (Grade 2-4) acute graft-versus-host disease (aGvHD)(Day 100 and Day 180 post-transplant)
- Cumulative incidence of severe (Grade 3-4) acute graft-versus-host disease (aGvHD)(Day 180 post-transplant)
- Graft-versus-host disease and relapse-free survival (GRFS)(1 year post-transplant)
- Incidence of chronic graft-versus-host disease (cGvHD(1 year post-transplant)
- Neutrophil engraftment(Up to Day 100 post-transplant)
- Platelet engraftment(Up to Day 100 post-transplant)
- Regimen-related toxicity(Up to Day 100 post-transplant)
- Transplant-related mortality (TRM)(1 year post-transplant)
- Overall survival (OS)(1 year post-transplant)
研究者
Dr Sachin Punatar
Professor & Medical Oncologist
Tata Memorial Centre