The goal of this observational study is to develop new ways to test new drug combinations to kill tumour cells, in patients with acute myeloid leukemia (AML). The main questions it aims to answer are:
* Are there new ways to speed up discovery of better treatments for AML patients using AML cells from individual from patients in special mice that can accept human tissue? * Do these mice show treatment responses that are similar to the individual AML patient from whom cells were derived?
Participants with AML who are taking standard of care treatment of venetoclax and azacitidine will be asked to donate blood and bone marrow samples for this study.
Age 18 years and above
Patients with suspicion of AML requiring screening procedures
Documented diagnosis of AML by WHO Classification and/or International Consensus Classification.
Regardless of the number and type of prior lines of therapy or eligibility for allogeneic stem cell transplantation.
None
Study population is people who have recently been diagnosed with or are suspected of having AML and undergoing investigational procedures, and whose doctor plans to start them on venetoclax and azacitidine. Around 25 people from different hospitals in Australia will take part in this project.
Cohort
Prospective
Not listed
Primary Endpoint - Generation of ≥20 adult AML PDX models with clinically annotated samples, including treatment regimen and clinical outcome
The outcome measures are 1) establish an adult AML PDX drug testing platform; 2) determine how accurately the AML PDX model replicates the clonal architecture and cellular characteristics of the original tumour by comparing donors' samples to AML PDX samples; 3) compare efficacy of standard of care and candidate therapies by engrafting multiple immune-deficient mice with the same donor sample; and 4) biomarker discovery through correlation of treatment response and single-cell and cytokine analysis.
Secondary Endpoint - Frequency and phenotype of leukemic cells measured by flow cytometry in AML PDX models and primary donor samples before and after VEN+AZA treatment.
A) Peripheral blood and bone marrow samples will be collected from Cohort 1 and Cohort 2 participants at baseline and relapse and will undergo molecular and cellular characterisation, these samples will be used to generate AML PDX models. B) Cells isolated from participant samples will be used to generate adult AML PDX models by reconstituting immune-deficient mice and expand the cell stock in vivo. Expanded cells will be used to reconstitute additional immune-deficient mice. C) Samples will be collected from immune-deficient mice before and after treatment to assess the efficacy of individual treatments. Participant and PDX samples will also be compared to assess the fidelity of the PDX model to their matching donor.
Click on the lead sponsor to view all of their trials.
Clinical Hub for Interventional Research (CHOIR)
Lead sponsor
Cancer Institute NSW
Collaborator
The University of New South Wales
Collaborator
Australian National University
Collaborator
