AML - Acute Myeloid LeukemiaCOSMOS-AvatarNCT06782971
Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX
An observational study of AML - Acute Myeloid Leukemia, run by Clinical Hub for Interventional Research (CHOIR) at 4 sites in Australia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML - Acute Myeloid Leukemia
- How many people
- 25 participants
- Where
- 4 sitesAustralia
- Study dates
- 6 Jun 2025to Mar 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Mark Polizzotto, Professor contact
Australia4 sites, 4 recruiting
- Recruiting
Canberra Health Services
Canberra, Australian Capital Territory, 2605
Samuel Bennett, Dr, samuel.k.bennett@act.gov.au
- Recruiting
Prince of Wales Hospital
Sydney, New South Wales, 2031
Mark Hertzberg, Professor
- Not yet recruiting
Royal North Shore Hospital
Sydney, New South Wales, 2065
Jad Othman, Dr
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Lachlin Vaughan, Dr
About this study
Official title: COSMOS-Avatar: Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX
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.
Read the 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.
- Conditions
- AML - Acute Myeloid Leukemia
- Keywords
- AML, Acute Myeloid Leukemia, PDX, Patient-derived xenografts
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Individuals diagnosed with or suspected of acute myeloid leukemia (AML) who are not planned for intensive chemotherapy and are commencing venetoclax + azacitidine therapy. | |
| Cohort 2 | Individuals who have relapsed following, or are refractory to, intensive chemotherapy or hematopoietic stem cell transplantation, commencing venetoclax + azacitidine therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)
Secondary outcomes (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.
- 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.
Measured: From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2025
- Study start6 Jun 2025
- Primary completionFeb 2028 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AML - Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Hub for Interventional Research (CHOIR)
- Sponsor type
- Other government
- Collaborators
- Cancer Institute NSW, The University of New South Wales, Australian National University
- Responsible party
- Sponsor
- Investigators
- John Pimanda, Professor, Principal investigator, University of New South Wales
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06782971
- Sponsor's protocol ID
- 24-M-003
- Acronym
- COSMOS-Avatar
- Status last verified
- Jun 2025
- First submitted
- 9 Jan 2025
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COSMOS-Avatar: Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX
- ClinicalTrials.gov ID
- NCT06782971
- Acronym / sponsor ID
- COSMOS-Avatar / 24-M-003
- Conditions
- AML - Acute Myeloid Leukemia
- Keywords
- AML, Acute Myeloid Leukemia, PDX, Patient-derived xenografts
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Clinical Hub for Interventional Research (CHOIR)Other government
- Collaborators
- Cancer Institute NSW, The University of New South Wales, Australian National University
- Study start
- 6 Jun 2025 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Mar 2030 (estimated)
- First posted
- 20 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | – | –Individuals diagnosed with or suspected of acute myeloid leukemia (AML) who are not planned for intensive chemotherapy and are commencing venetoclax + azacitidine therapy. |
| Cohort 2 | – | –Individuals who have relapsed following, or are refractory to, intensive chemotherapy or hematopoietic stem cell transplantation, commencing venetoclax + azacitidine therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (9 listed)
- 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.
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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)
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.
1 secondary outcome
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mark Polizzotto, Professor contact
John Pimanda, Professor principal investigator
University of New South Wales
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of AML - Acute Myeloid Leukemia, run by Clinical Hub for Interventional Research (CHOIR) at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John Pimanda, Professor (+61 000000000, cosmos.jcsmr@anu.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.