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.
Age > 1 year old and ≤18 years old at enrolment
Previously untreated
ALL diagnosis confirmed by morphology and flow-cytometry
Indian origins
Previously tretaed patients
Patients with Down's syndrome
Patients with mature B-ALL
Pediatric ALL patients
Cohort
Prospective
Not listed
Cumulative incidences of early treatment related adverse events as assessed by CTCAE v5.0
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.
Disease response to the treatment during induction phase to steroids
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
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
Assessment of quality of life using Pediatric Quality of Life Inventory questionnaires
Pediatric Quality of Life InventoryTM Generic Core version 4.0 and Pediatric Quality of Life InventoryTM Cancer Module Version 3.0 (translated and validated in local language i.e. Hindi and Tamil ). Both questionnaires are scored from minimum of 0 to maximum 100 with higher scores indicating higher health related quality of Life. will be used for quality of life assessment at the time of diagnosis, end of induction, beginning of maintenance phase and at day 100 of maintenance phase.
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University of Geneva, Switzerland
Lead sponsor
Jawaharlal Institute of Postgraduate Medical Education & Research
Collaborator
All India Institute of Medical Sciences
Collaborator
Swiss National Science Foundation
Collaborator
Ministry of Science and Technology, India
Collaborator
CANSEARCH Foundation
Collaborator
