Health Condition 1: C920- Acute myeloblastic leukemia
Conditions
Interventions
Intervention1: Venetoclax: Venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor, which is a type of targeted cancer therapy.
Duration: 14 days per cycle (Days 1 14)
Schedule:
Administered once daily
dosing starts at 200 mg/m^2 from Day 15
Control Intervention1: Azacitidine: Azacitidine is a chemotherapy drug classified as a demethylation agent and antimetabolite, primarily used to treat certain t
Sponsors
Dr Shyam Srinivasan
Eligibility
Inclusion criteria
Inclusion criteria: 1.Subject must have histological confirmation of AML by WHO criteria, with greater than 5 percentage bone marrow blasts. 2.Subject must have adequate renal function as demonstrated by a creatinine clearance greater than and equal to 30 mL/min, calculated by the Cockcroft Gault formula or measured by 24-hours urine collection. 3.Subject must have adequate liver function as demonstrated by: aspartate aminotransferase (AST) less than and equal to 5.0 ULN and alanine aminotransferase (ALT) less than and equal to 5.0 ULN and bilirubin less than and equal to 3 ULN (Unless considered to be due to Leukemic organ involvement).
Exclusion criteria
Exclusion criteria: 1.Age less than 1 year or greater than 15 years. 2.Previous chemotherapy for AML, except for cytoreductive therapy (hydroxyurea or low dose cytarabine for up to 96 hours). 3.Relapsed or refractory AML 4.Secondary AML 5.Subject has known CNS involvement with AML 6.Diagnosis of myelodysplastic neoplasm 7.Diagnosis of acute promyelocytic leukemia (APL, AML-M3) 8.Core-binding factor AML 9.Acute megakaryocytic leukemia 10.Children with Down syndrome 11.Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). 12.Subject has a white blood cell count greater than 25 10 to the power of 9 /L. (Note: Hydroxyurea or low-dose cytarabine for up to 96 hours administration or leukapheresis is permitted to meet this criterion). 13.Documented hypersensitivity to any component of the chemotherapy regimen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To estimate if two different venetoclax based combination therapies can improve composite complete remission (CR + CRi) rates in treatment na ve childhood AML. Timepoint: Baseline: Cycle 1 Day 1 (Pre-treatment). 4 Weeks: End of Cycle 1 (Day 28); first marrow evaluation. 8 Weeks: End of Cycle 2 (Day 56); Primary Endpoint analysis for composite complete remission (CR+CRi) | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine efficacy of venetoclax based combination regimens based on genomic subgroupsTimepoint: At the end of two cycles of venetoclax-based combination therapy. ;To evaluate if venetoclax based combination improves the minimal residual disease (MRD) response rate.Timepoint: MRD assessment at the end of cycles 1 and 2.;To evaluate the apoptotic priming and mitochondrial dependence of leukemic blasts in children with AML using BH3 profiling.Timepoint: Samples collected at baseline and end of cycle 1 for non-responders.;To assess the toxicity profile of venetoclax-based therapies. Timepoint: Continuous monitoring throughout the treatment period and for 30 days posttreatment.;To assess the 2-year event-free survival (EFS) and overall survival (OS) Timepoint: At 1 and 2 year from completion of intervention. | — |
Countries
India
Contacts
Public ContactDr Shyam Srinivasan
Tata Memorial Hospital
Outcome results
None listed