Randomised Controlled Trial of immunosuppressive therapy ATG+CSA with Eltrombopag ACE and ATG+CSA with Romiplostim in Aplastic Anemia & correlation of therapy response with transcriptomic profiling.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- The study will establish safety of combine therapy of ROM and IST vs ELT and IST as first line of therapy in Indian AA.
研究概览
简要总结
Aplastic Anemia (AA) can be treated with Hematopoietic Stem cells transplantation (HSCT) and Immune suppressive therapy (IST) but a lack of suitable donors and side effects of the drug impact the management of the study. Routinely, Antithymocyte globulin (ATG), Cyclosporine A (CSA) and Eltrombopag (ELT) known as ACE therapy is used in the treatment of AA, Long-term follow-up studies have reported hepatotoxicity in the subjects treated with Eltrombopag.
Romiplostim (ROM) in later studies have shown a good response in Immune thrombocytopenia (ITP) subjects and is well tolerated in AA subjects. However, its efficacy as a first-line treatment in combination with IST remains unexplored. A pilot study from India reported an effective response from ROM+ ATG + CSA in AA as first line therapy. This combination thus needs further evaluation with a large sample size and defined class of AA. Hence we have proposed to study AA subjects with the objectives of treatment two regimen (a) ATG+CSA+ELT (N=25) and (b) ATG+CSA+ROM (N=25), with follow up at 3 months, 6 months and 12 months. The genomic and transcriptomic changes are identified through next generation sequencing (NGS). The expected outcome of the study will measure the proportions of complete response (CR), Partial response (PR) and no response (NR). The study will also be establishing response rate of ROM+ATG +CSA as the first line therapy. Additionally, study will aid to understand the diverse transcriptomic patterns in responders and non-responder responsible for heterogeneity in BMF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- All
入选标准
- •Newly diagnosed acquired AA patients (Patients with hypocellular marrow i.e Less than 25% marrow cellularity; peripheral blood pancytopenia) of any gender aged 18 years to 45 years, willing for consent and follow up will be recruited for the study.
- •Negative for chromosomal breakages in MMC induced peripheral blood culture (negative for Fanconi’s anemia).
- •Willing to follow the study protocol.
- •No history of infections, chemical exposure or radiation therapy.
- •Treatment naive AA.
- •ECOG performance status 1-2.
排除标准
- •Aplastic anemia patients positive for chromosomal breakages in PHA stimulated, MMC induced peripheral blood cultures and other inherited bone marrow failure syndromes.
- •Secondary marrow aplasia (secondary to HSCT, drug or chemical exposure, radiotherapy, hepatitis), Patients with MDS Aplastic anemia Patients planning for HSCT.
- •History of allergy to the drug ingredients.
- •Participating in other drug clinical trials in the past 1 month.
- •Known case of Human Immunodeficiency Virus, active Hepatitis C infection or Hepatitis B infection.
- •Women who are pregnant or breast feeding or women of childbearing potential not willing to follow double contraceptive measures.
- •Any other reason that in the opinion of the investigator is likely to cause harm to the participant or will adversely affect the results of the study.
结局指标
主要结局
The study will establish safety of combine therapy of ROM and IST vs ELT and IST as first line of therapy in Indian AA.
时间窗: Time from recruitment to the primary outcome will be 6 months followed by 3 months follow up.
Proportion of patients with complete response (CR) (hematological CR defined by hemoglobin level more than 10 g/dL, absolute neutrophil count more than 1000 and platelets more than 100 X109 cells/L)
时间窗: Time from recruitment to the primary outcome will be 6 months followed by 3 months follow up.
Proportion of patients with partial response (PR) (PR defined as no longer meeting the criteria for SAA and transfusion independency with hemoglobin level more than 8 g/dL, absolute neutrophil count than 500, and platelet count more than20 X 109/L).
时间窗: Time from recruitment to the primary outcome will be 6 months followed by 3 months follow up.
Proportion of Non-responder (NR)(NR defined as any patient not meeting any of the response criteria defined above).
时间窗: Time from recruitment to the primary outcome will be 6 months followed by 3 months follow up.
次要结局
- The study will identify a differential gene expression pattern in AA patients treated with(TPO-R agonist (ELT or ROM) in combination with IST.)
- Identification of prime biomarkers in responders and non-responders at the time of(diagnosis.)
- Correlation of genomic changes and expression profile of AA patients with response and(non-response to the therapy.)
- To correlate response-based reticulocyte count, PNH clone, lineage specific differential(gene expression pattern identified through ScRNA seq.)
- Hematological profile at 3, 6 and 12 months.(3,6 and 12 months)
- Volume of blood and platelets transfused at the end of 3, 6 and 12 months (in case of(transfusion dependence).)
- To correlate the trough concentrations of ROM+IST with safety and efficacy parameters(3 Years)
- Change in quality of life at 6 months as assessed by Transfusion-dependent Quality of Life((TranQoL) questionnaire and the European Organization for Research and Treatment of)
- Incidence of treatment emergent adverse events [TEAEs] of grade 3 or more severity at 12(months [As per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0)
研究者
Dr Chandrakala Shanmukhaiah
Seth GS Medical College and KEM Hospital