Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX

NCT06782971 | Recruiting

• 1 other identifier: 24-M-003
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 4

Brief 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 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.

Conditions

AML - Acute Myeloid Leukemia

Keywords

AML; Acute Myeloid Leukemia; PDX; Patient-derived xenografts

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Clinical Hub for Interventional Research (CHOIR): lead
• Cancer Institute NSW: collaborator
• The University of New South Wales: collaborator
• Australian National University: collaborator

Study Sites (4)

Canberra Health Services

Canberra, Australian Capital Territory, 2605, Australia

RECRUITING

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

RECRUITING

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

NOT YET RECRUITING

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood and bone marrow aspirate research samples will be collected. After research samples have been processed, analysed, and stored for study endpoint evaluation, as specified in this protocol, the remaining specimens will be stored indefinitely for use in future related research.

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• John Pimanda, Professor

  University of New South Wales

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Pimanda, Professor

CONTACT

+61 000000000; cosmos.jcsmr@anu.edu.au

Mark Polizzotto, Professor

CONTACT

cosmos.jcsmr@anu.edu.au

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 20, 2025
• Study Start: June 6, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: December 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)