Use of Leflunomide as Primary Prophylaxis Against Cytomegalovirus (CMV) Reactivation in Haploidentical Haematopoietic Stem Cell Transplant (HIT) - Single, Arm, Phase 2 Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Number of participants with clinically significant cytomegalovirus (CMV) infection
研究概览
简要总结
Patients undergoing half-matched hematopoietic stem cell transplantation (HSCT) are at high risk of viral reactivation after bone marrow transplantation (BMT). The purpose of this study is to evaluate whether leflunomide can prevent cytomegalovirus (CMV) reactivation in these patients and to assess its safety.
The main questions it aims to answer are -
- Does leflunomide prevent cytomegalovirus (CMV) related organ damage?
- Does leflunomide prevent a rise in cytomegalovirus (CMV) copy number to more than 2000 copies/ml?
- Does leflunomide prevent the need to start pre-emptive therapy for cytomegalovirus (CMV)?
- Is it safe to use in bone marrow transplant ( BMT) patients?
- Does leflunomide prevent other viral reactivations - like Adeno virus and BK virus?
- Does leflunomide affect the risk of acute graft-versus-host disease ( acute GVHD) after bone marrow transplant (BMT)?
What medicine will the patients receive? Patients in study shall receive loading dose of Tab. Leflunomide 100 mg daily for 3 days followed by 20 mg daily orally. Leflunomide will be given till day +180 post transplant or till patient is on immunosuppressant medicines.
详细描述
Introduction :While pre-emptive medications have lowered the frequency of cytomegalovirus (CMV) illness after HSCT, CMV reactivation remains associated with higher mortality. Haploidentical transplant (haplo-HSCT) are high risk transplants, which have increased risk of viral reactivations. Current antiviral treatments, such as ganciclovir, have serious adverse effects and are limited in their use, whereas letermovir is expensive and unavailable in India.
Leflunomide, a medicine, which is used in Rheumatoid arthritis, is a possible alternative due to its antiviral effects and low cost. It may be beneficial at preventing cytomegalovirus (CMV) reactivation, particularly in patients with low viral levels. Furthermore, leflunomide has demonstrated efficacy against BK virus and other DNA viruses, making it a possible multifaceted preventive treatment for high-risk haplo-identical hematopoietic stem cell transplantation (HSCT) recipients.
Hypothesis Leflunomide is effective in decreasing clinically significant CMV(cytomegalovirus) infection after haplo-hematopoietic stem cell transplantation (HSCT)
Target population Patients ≥18 years of age who are undergoing haplo-hematopoietic stem cell transplantation (HSCT) for any malignancy at Tata Memorial centre ACTREC, Mumbai
Aims:
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
- •Males or females undergoing Haplo-identical haematopoetic stem cell transplant.
- •Age ≥18yrs on the day of signing informed consent
- •Undetectable CMV from plasma sample in preceding 7 days
- •Patient who has WBC engraftment (ANC>=500/cumm for 3 or more consecutive days).
- •Within 7 days of WBC engraftment
- •Adequate liver functions (ALT / AST less than 5 times upper limit of normal and Bilirubin <=3 times upper limit of normal) at time of starting leflunomide
- •Understands the study procedures, alternative treatment available, and risks involved with the study, and voluntarily agree to participate by giving written informed consent.
排除标准
- •Known hypersensitivity to Leflunomide
- •History of clinically significant CMV reactivation in past 1 year
- •Patient is receiving/has received drug known to have anti CMV activity within in last 7 days [Ganciclovir, valganciclovir, foscarnet, letermovir, acyclovir (at doses >=3200 mg PO per day or >=25 mg/kg IV per day), valacyclovir (at doses &>=3000 mg PO per day)]
- •Inadequate renal function (creatinine clearance <=30 ml/min)
- •Chronic active hepatitis B (HBsAg+ or any HBV DNA+), hepatitis C, or/and HIV
- •Any psychiatric condition that might limit the ability of the patient to comply with the protocol
结局指标
主要结局
Number of participants with clinically significant cytomegalovirus (CMV) infection
时间窗: Through Day +180 post hematopoietic stem cell transplantation (HSCT).
Number of participants with clinically significant cytomegalovirus (CMV) infection through Day +180 after hematopoietic stem cell transplantation (HSCT). Clinically significant CMV infection is defined as the occurrence of one or more of the following: Cytomegalovirus (CMV) end-organ disease; Cytomegalovirus (CMV) viremia ≥2,000 copies/mL measured by the central laboratory; or Initiation of pre-emptive anti-CMV therapy at the investigator's discretion.
次要结局
- Number of participants with treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0(Day+180 post transplant)
- Number of participants with clinically significant BK virus reactivation(Day+180 post transplant)
- Number of participants with Grade III-IV acute graft-versus-host disease(Day+180 post transplant)
研究者
Dr Lingaraj Nayak
Professor, Medical Oncology
Tata Memorial Centre