Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX

Официальное название

COSMOS-Avatar: Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML PDX

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Primary Endpoint - Generation of ≥20 adult AML PDX models with clinically annotated samples, including treatment regimen and clinical outcome [Срок оценки: From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)]

Вторичные конечные точки (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. [Срок оценки: From enrolment (i.e., C1D1 of Ven+AZA treatment) up to end of treatment or 52 weeks post C1D1 (whichever applies first)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Австралия · 4 центра

• Canberra Health Services — Canberra
• Prince of Wales Hospital — Sydney
• Royal North Shore Hospital — Sydney
• Westmead Hospital — Westmead

Идентификаторы

NCT: NCT06782971 · 24-M-003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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