Home> Research Projects> AML-5: Exploring a role for HARMONY data as historical control in elderly Acute Myeloid Leukemia patients.

AML-5: Exploring a role for HARMONY data as historical control in elderly Acute Myeloid Leukemia patients.

AML, HARMONY, Leukemia

Challenge

Acute Myeloid Leukemia (AML) is a heterogeneous disease consisting of many cytogenetic and molecular subgroups with different clinical outcomes. AML predominantly affects the elderly (median age at diagnosis 68 years) and can present with a variety of patient- and disease-related challenges in comparison to younger patients. Conducting randomized controlled trials (RCTs) in elderly AML can be challenging as treatment must be tailored to different subtypes, hence recruitment takes longer and studies can be underpowered because of small patient numbers.

Project Partnership

Project Leadership

Carin A. Uyl-de Groot, Erasmus MC
Jan J. Cornelissen, Erasmus MC
Gert Ossenkoppele, Amsterdam UMC

Impact

To establish proof-of-concept for the use of HARMONY data from already completed RCTs as a historical control/comparator for future clinical studies.
The potential use of historical data as a control arm will increase the available population for experimental arms.
This approach could then expedite drug development and approval of new treatments for AML by regulators.

Project Summary

RCTs are used to evaluate the clinical value of treatments to minimize confounding factors that might influence treatment outcomes. However, an emerging question is whether RCTs are realistic, given the fact that the treatment is becoming increasingly tailored and studies are of extensive duration. To overcome this problem, data from existing RCTs and the real-world data be used as comparators for new interventions. This study will help explore and compare the outcomes of elderly AML control patients in the HARMONY database with patients in the control group of the most recent HOVON-103 study. HOVON is the Heamato Oncology Foundation for Adults in the Netherlands.

The selection of patients from the HARMONY database will be based on the eligibility criteria of the HOVON-103 study. The eligibility criteria are:
•   Newly diagnosed with AML
•   Patients aged ≥66 years
•   Treated with first-line intensive chemotherapy regimens

Clinical data from at least 3–5 distinct trials in the HARMONY database will be included, with the key variables identified for each patient. The main outcome parameters will be patient characteristics, prognostic factors, complete remission rate, event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS). OS will be determined using Kaplan-Meier analysis and RFS will be calculated using competing risk analysis. The survival outcomes for confounders will be adjusted using Cox regression.

As the HARMONY Big Data Platform is the largest AML registry in Europe this analysis would significantly help create a reference for further trials in AML therapies.

Public-private partnership for Big Data in Hematology

HARMONY and HARMONY PLUS are funded through the Innovative Medicines Initiative (IMI), Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. Funding is received from the IMI 2 Joint Undertaking and is listed under grant agreement for HARMONY No. 116026 and grant agreement for HARMONY PLUS No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA).