A Phase II Clinical Trial of Standardized Withaferin-A for the Treatment of Steroid Refractory Acute Graft Versus Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- OBJECTIVE RESPONSE RATE (ORR)
研究概览
简要总结
Study Design Prospective, single center, single arm, Phase II study.
Research aims and objectives Aim:
To evaluate the efficacy and safety of standardized Withaferin A in steroid refractory acute GvHD in patients post allogeneic stem cell transplantation
Primary Objective:
To evaluate the objective Response Rate (ORR) at Day 28 from the start of SWA defined as the proportion of patients achieving Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR).
Methodology
Treatment plan and Interventions Administration of study treatment Name of the intervention: Standardized WA (standardized root extract of Withania somnifera. This will be provided free of cost to the trial patients.
Formulation: The standardized root extract of W. somnifera contains 5% of WA w/w. SWA is available as a 500 mg capsule (AshwaMAX) that contains 25 mg of WA.
Route of administration: Per-oral (P/O) Dose schedule: The dose of SWA is 1500mg/day. It will be administered as 3 capsules of 500 mg once a day.
Duration of treatment:
- Every patient will receive treatment for at least 12 weeks followed by a taper as per physician's discretion. WA can be tapered after 12 weeks if the patient has achieved CR or VGPR and has discontinued corticosteroids for at least 4 weeks.
- Dose adjustments/modifications: If the patient experiences any grade ≥3 toxicities related to SWA, further administration of SWA will be withheld immediately. Once the severity of the adverse event reduces to grade ≤1, the study agent will be rechallenged with 25% dose reduction. The same strategy will be adopted for successive grade ≥3 toxicities. If the drug is not tolerated at 25% of original dose (100 mg), no further rechallenge will be attempted.
- Corticosteroid tapering will be done as per the treating physician's discretion and clinical condition of the patient.
详细描述
Secondary Objectives:
- To evaluate the ORR at other defined time points (Day 14 and Day 56) from initiation of SWA
- To study the Non relapse Mortality (NRM) at 1 year post transplant
- To study the Relapse rate at 1 year post transplant
- To study the Overall Survival (OS) at 1 year post transplant
- To study the incidence of chronic GvHD at 1 year post transplant
- To study the incidence of adverse effects attributed to SWA
Exploratory Objectives:
- Reduction of steroid dose by ≥30% from baseline will be calculated for all patients on day 28 after start of SWA.
- To measure the JAK2-STAT3 levels, JAK2-STAT3 receptor kinetics at baseline (pre- conditioning) and post initiation of WA.
- Immune cell phenotype, cytokine profile and pharmacokinetics of WA in patients post treatment with SWA at baseline, Day +7, Day +14, Day +28, Day+56, Day+90 and Day +180 post HSCT.
What is acute Graft versus host disease (GvHD)? GvHD is a complication that can occur after an allogeneic stem cell transplant resulting in damage to internal organs. Patients with GvHD have a mortality rate of 15-40%. In GvHD, the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow harm the body. Acute GvHD usually develops in the skin, liver or gastrointestinal tract, and symptoms might appear within weeks after transplant. Symptoms of acute GvHD are skin rash or reddened areas on the skin, yellow discoloration of the skin and/or eyes, and abnormal blood test results, nausea, vomiting, diarrhea, or abdominal cramping.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age ≥ 12 years with a hematological malignancy who have undergone allogeneic stem cell transplant with matched related donor (MRD), Haploidentical (Haplo) donor or matched unrelated donor (MUD)
- •Evidence of myeloid engraftment (eg, absolute neutrophil count ≥0.5 × 109 /L for 3 consecutive days)
- •ECOG performance score of 0 or 1
- •Patients with steroid-refractory aGvHD, defined as any of the following:
- •Patients with progressive GvHD (ie, increase in stage in any organ system or any new organ involvement) after 3 days of primary treatment with methylprednisolone ≥2 mg/kg/d (or equivalent)
- •Patients with GvHD that has not improved (ie, decrease in stage in at least 1 involved organ system) after 7 days of primary treatment with methylprednisolone ≥2 mg/kg/d (or equivalent)
- •Patients who previously began corticosteroid therapy at a lower dose (≥1 mg/kg/d methylprednisolone) for treatment of skin GvHD or skin GvHD accompanied by upper gut GvHD but develop new GvHD in another organ system
- •Patients who cannot tolerate a corticosteroid taper, that is, begin corticosteroids at 2.0 mg/kg/d, demonstrate response, but progress before a 50% decrease from the initial starting dose of corticosteroids is achieved
排除标准
- •Known hypersensitivity or contraindications against Withaferin-A.
- •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.
结局指标
主要结局
OBJECTIVE RESPONSE RATE (ORR)
时间窗: Day 28 after initiation of standardized Withaferin A (SWA)
OBJECTIVE RESPONSE RATE (ORR)
次要结局
- Overall response rate(Day 14 and Day 56 after initiation of standardized Withaferin A)
- Non-relapse mortality (NRM)(Up to 1 year post-transplant)
- Overall survival (OS)(Up to 1 year post-transplant)
- Incidence of chronic graft versus host disease(Up to 1 year post-transplant)
- Incidence of adverse effects(until 12 weeks after last dose of Investigational product)
- Relapse rate(upto 1 year post transplant)
研究者
Akanksha Chichra
FNB DNB Pediatric oncologist
Tata Memorial Centre