Using patient-derived mouse models to find drugs that make venetoclax plus azacitidine work better in AML
COSMOS-Avatar: Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX
This project will test whether adding sensitizing drugs to venetoclax and azacitidine helps kill leukemia cells in people with AML by using patient-derived mouse models.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 25 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Clinical Hub for Interventional Research (CHOIR) Government |
| Drugs / interventions | chemotherapy |
| Locations | 4 sites (Canberra, Australian Capital Territory and 3 other locations) |
| Trial ID | NCT06782971 on ClinicalTrials.gov |
What this trial studies
This observational program collects blood and bone marrow from adults with AML who are starting venetoclax plus azacitidine and uses those samples to create patient-derived xenograft (PDX) mouse models. Researchers will test multiple candidate drug combinations alongside standard-of-care in the PDX avatars to identify combinations that better kill tumor cells with minimal harm to healthy blood cells. The study will compare how the mice respond to treatments with how the original patient responded, and promising combinations will be moved into a separate Phase I clinical trial platform. Samples will be collected over up to two years through altruistic donation to build a drug-testing platform aimed at guiding precision therapies.
Who should consider this trial
Good fit: Adults aged 18 and over with confirmed AML who are planned to start venetoclax plus azacitidine and can provide informed consent and blood or bone marrow samples are ideal candidates.
Not a fit: Patients who are not starting venetoclax plus azacitidine, cannot provide samples, have conditions that prevent safe participation, or whose samples fail to engraft in mice are unlikely to receive direct benefit.
Why it matters
Potential benefit: If successful, this could identify better drug combinations tailored to a patient’s leukemia and speed the most promising options into early clinical trials.
How similar studies have performed: PDX models have been valuable in preclinical drug testing and have sometimes predicted patient responses, but using them routinely to guide individual patient therapy is still relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Age 18 years and above 2. Patients with suspicion of AML requiring screening procedures 3. 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. 4. 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. 5. Planned to commence venetoclax and azacitidine therapy. 6. 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.
Where this trial is running
Canberra, Australian Capital Territory and 3 other locations
- Canberra Health Services — Canberra, Australian Capital Territory, Australia (Recruiting)
- Prince of Wales Hospital — Sydney, New South Wales, Australia (Recruiting)
- Royal North Shore Hospital — Sydney, New South Wales, Australia (Not_yet_recruiting)
- Westmead Hospital — Westmead, New South Wales, Australia (Recruiting)
Study contacts
- Principal investigator: John Pimanda, Professor — University of New South Wales
- Study coordinator: John Pimanda, Professor
- Email: cosmos.jcsmr@anu.edu.au
- Phone: +61 000000000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.