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
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD
研究概览
简要总结
Brief summary
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.
Study synopsis
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.
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.
Objectives: To evaluate the GvHD prophylactic effect of reduced dose PTCy in combination with Calcineurin inhibitors and MMF for haploidentical HSCT.
Methods: Following patient enrolment and drug administration the GvHD grade, engraftment kinetics, cytokine profile and immune reconstitution will be evaluated.
Expected Outcome: Combination of reduced dose PTCy with calcineurin inhibitors and MMF may be equally effective in reducing severe aGvHD as standard dose PTCy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •1.ECOG performance score of 0 or 1.
排除标准
- •1.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.
- •2.Any medical or psychiatric illness which precludes the participant from giving informed consent.
- •b.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) equal to or less than 50 percent of predicted (corrected for haemoglobin).
- •c.Serious renal dysfunction: Measured serum creatinine clearance equal to or less 60 mL per min.
- •d.Serious Hepatic dysfunction: Total serum bilirubin more than twice upper normal limit or Alanine aminotransferase (ALT) or aspartate aminotransferase.
结局指标
主要结局
To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD
时间窗: at day 100 Post Transplant
次要结局
- 1.To evaluate the cumulative incidence of clinically significant (Grade2-4) aGvHD at Day 100 and Day 180.(2.To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD at Day 180.)
研究者
Dr Sachin Punatar
Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre