Pharmacogenomic Association Study in Indian Children With Acute Lymphoblastic Leukemia

NCT05512169 | Recruiting DMC

• 1 other identifier: MPGx-INDALL
• Study Type: observational
• Target: 556
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

ALL, Childhood; Pediatric Cancer; Toxicity, Drug; Adverse Drug Event; Relapse Leukemia; Drug Toxicity; Drug Effect; Drug Interaction

Keywords

Pharmacogenetics; Pharmacogenomics; Genetic polymorphism; Sequencing; Genotyping; Indian; Pediatrics; SNP; gene variant; germline genetic variant; somatic variant; biomarker; steroid response; genetic predisposition

Outcome Measures

Primary Outcomes (3)

• 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.

  10-12 months varying depnding upon the risk category

• 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.

  Day 8 of induction phase

• 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

  Day 35 of induction phase

Secondary Outcomes (1)

• Assessment of quality of life using Pediatric Quality of Life Inventory questionnaires

  10-12 months

Study Arms (1)

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.

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric ALL patients

You may qualify if:

• Age \> 1 year old and ≤18 years old at enrolment
• Previously untreated
• ALL diagnosis confirmed by morphology and flow-cytometry
• Indian origins
• Written Informed consent to participate in the study has to be signed by the participant/parent/guardian

You may not qualify if:

• Previously tretaed patients
• Patients with Down's syndrome
• Patients with mature B-ALL

Sponsors & Collaborators

• University of Geneva, Switzerland: lead
• CANSEARCH Foundation: collaborator
• 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

Study Sites (2)

Dr. Sameer Bakhshi

New Delhi, 110029, India

RECRUITING

Dr. Biswajit Dubashi

Puducherry, 605006, India

RECRUITING

Related Publications (2)

• Chenchula S, Atal S, Uppugunduri CRS. A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care. Pharmacogenomics J. 2024 Mar 15;24(2):9. doi: 10.1038/s41397-024-00326-1.

  PMID: 38490995 BACKGROUND

• Kodidela S, Dorababu P, Thakkar DN, Dubashi B, Sundaram R, Muralidharan N, Nidanapu RP, Aribandi A, Pradhan SC, Uppugunduri CRS. Association of NUDT15*3 and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia. Genes (Basel). 2020 May 28;11(6):594. doi: 10.3390/genes11060594.

  PMID: 32481505 RESULT

Related Links

• Pilot study results prior to initiating this prosepctive study

Biospecimen

Retention: SAMPLES WITH DNA

Germ line DNA from saliva or whole blood at Remission Somatic DNA from bone marrow Plasma at baseline, end of induction and other phases of the treatment , Enrollment status: as on 14.01.2026: Actual number of participants enrolled at AIIMS center: 223 (204 evaluable); Actual number of participants enrolled at JIPMER center: 136 (130 evaluable)

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chemically-Induced Disorders; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Chakradhara Rao S UPPUGUNDURI

  University of Geneva

  PRINCIPAL INVESTIGATOR

• Biswajit DUBASHI

  Jawaharlal Institute of Postgraduate Medical Education & Research

  PRINCIPAL INVESTIGATOR

• Sameer BAKHSHI

  All India Instiutte of Medical Scineces

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chakradhara Rao S Uppugudnuri

CONTACT

+41223794685; chakradhara.uppugunduri@unige.ch

Marc Ansari

CONTACT

+41223724731; Marc.Ansari@hcuge.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Collaborator Scientific II & Principal Investigator

Study Record Dates

• First Submitted: June 20, 2022
• First Posted: August 23, 2022
• Study Start: December 1, 2022
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2027
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

IN (2)