Master Framework For Relapse or Refractory Acute Myeloid Leukemia

Treatment outcome for acute myeloid leukemia (AML) has improved over the last few decades. With intensive multidrug induction regimens, a complete remission is expected. Despite such advances, therapy resistance or relapse remains the main causes of death in adult patients and in children. Relapsed or refractory (R/R) AML is a hard-to-treat disease, with a 5-year overall survival (OS) estimate below 20% in adults and 30%-35% in children, and no standard of care exists. HSCT (allogeneic hematopoietic stem cell transplantation) remains the only curative strategy for R/R AML patients, including pediatric and elderly ones. Some new personalized therapies have recently been integrated into the treatment options of R/R AML. However, there is a need to collect consistent data on the efficacy of these new strategies in real-world settings. Lack of data from clinical trials can be a barrier in most countries, limiting patient accessibility to some very effective drugs. The STREAM study is part of the Horizon Europe Mission Cancer 2022 IMPACT-AML project, that proposes to create an inclusive master framework for relapsed or refractory acute myeloid leukemia. In STREAM we will collect data and monitor outcomes of patients with R/R AML across Europe. In close collaboration with the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet, GA101157011), STREAM is developed under ERN-EuroBloodNet central registry, the European Rare Blood Disorders Platform (ENROL), incorporating EU standards for interoperability and the GPDR-compliant SPIDER pseudonymization tool offered by the EU-RD Platform in the context of rare disease registries will be implemented, to allow cross-hospital and cross-country participation. The STREAM study will allow to collect high-quality data from patients at any stage of the disease, for any cancer subtype, in any age group, including pediatric and elderly population, unfit patients, patients with rare mutations, patients with high-impact end-organ damage, patients from rural regions, post-transplant relapse. Data collected in STREAM will foster the production of novel knowledge on rare populations in a pragmatic setting and will form the basis for building international trials to be conducted worldwide.

• Registration into the STREAM platform (Other): All patients fulfilling eligibility criteria will be registered into the STREAM platform. Baseline and follow up information will be recorded for each patient enrolled. Each patient will be followed up according to normal clinical practice up to 4 years.

Primary outcomes

• The primary endpoint is to determine the overall survival of R/R AML patients [8 years]: Overall survival is defined as the time from R/R diagnosis to death due to any cause.

Secondary outcomes

• Remission rate [8 years]: Response is defined according to ELN 2022 criteria. Rates of CR, CRi, CRh and overall response (CR+CRi+CRh) as best response will be considered
• Event-free survival [8 years]: Event-free survival is defined as the time from R/R diagnosis to rescue treatment failure (according to ELN 2022 definitions), relapse or death due to any cause, whichever occurs first.
• Relapse free survival [8 years]: Relapse-free survival is defined for patients achieving a response to rescue treatment as the time from response onset to relapse or death due to any cause, whichever occurs first.
• Transplant rate [8 years]: Proportion of patients undergoing transplantation
• Describe the methods for diagnosis and the treatment options offered to the patients affected by R/R AML [8 years]: type and frequency of diagnostic procedures used and treatments prescribed
• Association between baseline clinical, molecular and biological parameters and clinical outcomes [8 years]: Rates of CR, CRi, CRh and overall response (CR+CRi+CRh) in specific sub-populations bearing common molecular features
• To characterize potential populations that could be target for future studies/clinical trials [8 years]: descriptive statistics (mean, median, frequency, range) of subpopulations characteristics

Sex: All, ages: 6 Years to any

Inclusion Criteria:

* Patients with AML diagnosis according to WHO2022 or ICC2022
* Treatment failure (i.e. relapse, refractory or progression, including MRD) according to ELN2022 criteria
* Participant or his/her legal representative is willing and able to give informed consent for participation in the study

Exclusion Criteria:

* Patients included in clinical trials may be enrolled except where otherwise specified in the experimental protocol.

• Giovanni Martinelli, MD, Prof, Study chair, University of Bologna