Molecular and Pharmacogenetic Marker Evaluation in Relation to the Toxicity and Clinical Response of Acute Lymphoblastic Leukemia Treatment in Indian Children (MPGx-INDALL)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 556
- 试验地点
- 2
- 主要终点
- Disease response to the treatment during induction phase to steroids
研究概览
简要总结
A five-year prospective observational cohort study. The study is focused on observing the relation between static germline variants and therapeutic response in Indian children with acute lymphoblastic leukemia (ALL). The project is an International multicenter setup. This collaborative research project between Switzerland and India includes one main center in Geneva that has conceptualized, designed, received grants for the study and two investigating centers in India (Puducherry and New-Delhi) involved in study design, patient care and recruitment for this specific study. All the participants for the study will be recruited form these two centers in India, and no patient recruitment is planned at main center i.e. Geneva.
The study will be conducted in two phases. The first aims to investigate genetic predisposition (static germline variants) to early chemotherapy treatment related toxicities (TRTs). The second aims to investigate somatic genetic markers associated with the efficacy of steroid treatment among patients undergoing the standardized IciCLe-ALL-14 treatment protocol. A total of 500 children with ALL will be recruited to investigate primary objective of the study i.e. TRT, and a subset of 250 patients will be included to investigate another research question i.e. response to steroid therapy.
详细描述
Primary objectives:
- To study the associations of static germline variants with early chemotherapy-related toxicities (treatment related toxicities) in children with ALL undergoing the Icicle treatment protocol.
- To investigate the somatic and germline genetic markers associated with the efficacy and toxicity of glucocorticoid response, respectively.
- To biobank biological samples and clinical data for future association analyses in order to develop biomarkers of the treatment protocol's efficacy and toxicity.
Secondary Objectives:
- To study the impact of the occurrence of early toxicities on quality of life during active ALL treatment (physical and emotional quality of life using the PedsQL tool).
- To evaluate genetic associations (somatic and germline) with overall survival, non-relapse mortality, relapse free survival, and event-free survival.
Clinical outcomes:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 1 year old and ≤18 years old at enrolment
- •Previously untreated
- •ALL diagnosis confirmed by morphology and flow-cytometry
- •Indian origins
- •Fulfilling IciCle treatment protocol inclusion criteria and receiving treatment as per the protocol
- •Written Informed consent to participate in the study has to be signed by the participant/parent/guardian
排除标准
- •Previously tretaed patients
- •Patients with Down's syndrome
- •Patients with mature B-ALL
研究组 & 干预措施
Newly diagnosed ALL Children with age group of >1 and ≤18 years old
Newly diagnosed ALL Children who are likely to receive anti-cancer drugs or chemotherapy as a part of IciCLE treatment protocol.
结局指标
主要结局
Disease response to the treatment during induction phase to steroids
时间窗: Day 8 of induction phase
Prednisolone response on day 8th of the induction: Good response if peripheral blast count \<1000/uL or Poor response if it is \> 1000 /uL.
Disease response to the treatment during induction phase
时间窗: Day 35 of induction phase
Bone marrow on Day 35: in remission = \<5% blasts ; 5-25% blasts= M2 marrow; \>25% blasts= M3 marrow MRD (flow cytometry) testing on Day 35: =\>0.01 % = high MRD ; \<0.01% negative MRD
Cumulative incidences of early treatment related adverse events as assessed by CTCAE v5.0
时间窗: 10-12 months varying depnding upon the risk category
Drug-related toxicity ≥ grade 3 occurring from the first day of induction until the middle of maintenance therapy. Cumulative incidences of neutropenia from day 1 of maintenance to day 100 of maintenance therapy. Incidences of multiple drug related adverse events of grade 3 and above as assessed by CTCAE v5.0 before day 100 of maintenance phase. Incidences of 14 severe acute toxic effects as defined by Ponte di Legno toxicity working group consensus definitions (Ref: Lancet Oncol 2016;17:e231-e239) Drug causality for the adverse event and grade at onset , maximum grade, and date of resolution will be considered. Assessment of biochemical tests to consider for toxicity assessment as per CTCAE criteria will be performed every week until the maintenance phase, and then once in two weeks from day 1 to day 100 of maintenance phase.
次要结局
- Assessment of quality of life using Pediatric Quality of Life Inventory questionnaires(10-12 months)
研究者
Uppugunduri S Chakradhara Rao
Collaborator Scientific II & Principal Investigator
University of Geneva, Switzerland