Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India
Abstract Background In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protoc...
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BMC
2022-01-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-022-06033-1 |
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| author | Nandana Das Shripad Banavali Sameer Bakhshi Amita Trehan Venkatraman Radhakrishnan Rachna Seth Brijesh Arora Gaurav Narula Subir Sinha Prakriti Roy Manash Pratim Gogoi Sayan Chatterjee Bindhu Abraham Parag Das Vaskar Saha Shekhar Krishnan |
| author_facet | Nandana Das Shripad Banavali Sameer Bakhshi Amita Trehan Venkatraman Radhakrishnan Rachna Seth Brijesh Arora Gaurav Narula Subir Sinha Prakriti Roy Manash Pratim Gogoi Sayan Chatterjee Bindhu Abraham Parag Das Vaskar Saha Shekhar Krishnan |
| author_sort | Nandana Das |
| collection | DOAJ |
| description | Abstract Background In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. Methods Patients 1–18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 109/L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. Discussion ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. Trial registration Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015 |
| first_indexed | 2024-12-10T16:23:21Z |
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| id | doaj.art-eb1369a80be34976944007a96161b1e7 |
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| language | English |
| last_indexed | 2024-12-10T16:23:21Z |
| publishDate | 2022-01-01 |
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| series | Trials |
| spelling | doaj.art-eb1369a80be34976944007a96161b1e72022-12-22T01:41:46ZengBMCTrials1745-62152022-01-0123112010.1186/s13063-022-06033-1Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in IndiaNandana Das0Shripad Banavali1Sameer Bakhshi2Amita Trehan3Venkatraman Radhakrishnan4Rachna Seth5Brijesh Arora6Gaurav Narula7Subir Sinha8Prakriti Roy9Manash Pratim Gogoi10Sayan Chatterjee11Bindhu Abraham12Parag Das13Vaskar Saha14Shekhar Krishnan15Clinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreDepartment of Pediatric Oncology, Tata Memorial Centre, Tata Memorial HospitalDepartment of Medical Oncology, All India Institute of Medical SciencesPediatric Hematology-Oncology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and ResearchDepartment of Medical Oncology, Cancer Institute (WIA)Department of Pediatrics, All India Institute of Medical SciencesDepartment of Pediatric Oncology, Tata Memorial Centre, Tata Memorial HospitalDepartment of Pediatric Oncology, Tata Memorial Centre, Tata Memorial HospitalDepartment of Statistics, Tata Medical CenterClinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreClinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreClinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreTata Consultancy ServicesClinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreClinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreClinical Research Unit, Tata Translational Cancer Research Centre, Tata Medical CentreAbstract Background In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. Methods Patients 1–18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 109/L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. Discussion ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. Trial registration Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015https://doi.org/10.1186/s13063-022-06033-1Acute lymphoblastic leukaemiaChildhoodRandomised trialRisk stratificationOpen label |
| spellingShingle | Nandana Das Shripad Banavali Sameer Bakhshi Amita Trehan Venkatraman Radhakrishnan Rachna Seth Brijesh Arora Gaurav Narula Subir Sinha Prakriti Roy Manash Pratim Gogoi Sayan Chatterjee Bindhu Abraham Parag Das Vaskar Saha Shekhar Krishnan Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India Trials Acute lymphoblastic leukaemia Childhood Randomised trial Risk stratification Open label |
| title | Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India |
| title_full | Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India |
| title_fullStr | Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India |
| title_full_unstemmed | Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India |
| title_short | Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India |
| title_sort | protocol for icicle all 14 inpog all 15 01 a prospective risk stratified randomised multicentre open label controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in india |
| topic | Acute lymphoblastic leukaemia Childhood Randomised trial Risk stratification Open label |
| url | https://doi.org/10.1186/s13063-022-06033-1 |
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