Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: AML - Acute Myeloid Leukemia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
COSMOS-Avatar: Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX
Overview
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.
Detailed description
Treatment options for patients with acute myeloid leukemia (AML) who are unfit or refractory to intensive chemotherapy, or who have relapsed after hematopoietic stem cell transplantation, remain limited. Hypomethylating agents (HMAs) are effective in prolonging patient survival, but they are often associated with adverse events and their therapeutic effects are temporary. By elucidating the resistance mechanisms used by AML cells, we have identified drugs that selectively sensitise these tumour cells to HMAs, with minimal toxicity to healthy blood cells. Patient-derived xenografts (PDX) have emerged as a valuable tool for drug testing in cancer research. They can better replicate the primary tumour and its environment in vivo, mimicking the disease progression and treatment responses of their corresponding donor with superior fidelity and predictive potential compared to current in vitro systems. The COSMOS-Avatar study aims to establish a drug testing platform to guide precision therapies tailored to defined tumour profiles. Tumour cells obtained over two years through altruistic donation for research will be used to generate AML PDX mouse models or avatars that will be used to compare standard of care and multiple candidate therapies simultaneously. Promising drug combinations identified through the COSMOS-Avatar study will proceed to a dedicated independent Phase I clinical trial platform to accelerate drug discovery and development of AML therapies.
Primary outcome measures
- Primary Endpoint - Generation of ≥20 adult AML PDX models with clinically annotated samples, including treatment regimen and clinical outcome [Time frame: From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)]
Secondary outcome measures (1)
- 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. [Time frame: From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)]
Eligibility criteria
Inclusion criteria
- 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.
- All AML subtypes are eligible.
- Concurrent participation in clinical trials is allowed.
- Documented myeloblast percentage ≥20% in the bone marrow or peripheral blood within 12 weeks of C1D1 confirmed by bone marrow aspirate or peripheral blood smear.
- Planned to commence venetoclax and azacitidine therapy.
- Provision of written informed consent prior to any study-related assessments or procedures being carried out.
Exclusion criteria
1\. Presence of any condition that, by assessment of the Investigator, would compromise the safety of the patient if they participated, the quality of trial data, or their adherence to the study-specified procedures.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Australia · 4 centers
- Canberra Health Services — Canberra
- Prince of Wales Hospital — Sydney
- Royal North Shore Hospital — Sydney
- Westmead Hospital — Westmead
Identifiers
NCT: NCT06782971 · 24-M-003