Clinical trial NCT03549351: Evaluation of Measurable Residual Disease in Patients With Acute Myeloid Leukemia as Surrogate Endpoint for Survival
Official title: Prospective Evaluation of Measurable Residual Disease in Intensively Treated Patients With Acute Myeloid Leukemia (AML) as Surrogate Endpoint for Survival
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Leukemia, Myeloid, Acute
Keywords: Leukemia, Myeloid, Acute
measurable residual disease
surrogate endpoint
multiparameter flow cytometry
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: University Hospital Dresden
name: German Cancer Research Center
First posted: 2018-06-08
Enrollment: 51
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with AML participating in interventional prospective randomized trials of the Study Alliance Leukemia (SAL) including the Heidelberg Leukemia Network (HeLeNe)

Brief summary: Objectives To demonstrate that measurable residual disease assessed by multiparameter flow cytometry during intensive treatment is a surrogate for overall survival and thus an early read-out for drug efficacy Study design Surrogate endpoint trial to establish that measurable residual disease assessed by multiparameter flow cytometry during intensive treatment is a surrogate for overall survival

Detailed description: Acute myeloid leukemia is a genetically and phenotypically heterogeneous disorder with an incidence of 3 to 4 per 100 000 men and women per year and a median age at diagnosis of about 70 years. Prognosis, especially in older patients, has remained very poor. In patients considered suitable for intensive chemotherapy, the combination of an anthracycline and cytarabine remains the standard of care. For patients achieving a complete remission (CR), postremission therapy (PRT) ranging from chemotherapy to allogeneic hematopoietic stem cell transplantation is required; intensive PRT is still under debate in older patients. Beyond pre-treatment genetics-based risk stratification, measurable residual disease (MRD) during treatment and follow up emerges as an important prognostic factor in first CR. Furthermore, MRD may provide a tool for a read-out of therapeutic efficacy. In this diagnostic meta-study the investigators intend to measure MRD using multiparameter flow cytometry across up-front randomized clinical trials which in total will accrue more than 1000 patients. According to the leukemia-associated phenotype at diagnosis or the different-from-normal approach, MRD will be assessed early (after induction) and late (after consolidation) during treatment. The aim of the study is to show that levels of MRD measured early during treatment are closely related to overall survival and thus may serve as an early surrogate. There is a growing public demand that new, promising drugs are approved for therapy as rapidly as possible. Therefore, it is of great interest to obtain these approvals based on early biomarker endpoints such as MRD rather than on long-term survival endpoints.

Eligibility criteria: Inclusion Criteria:

* Acute myeloid leukemia according to the WHO classification
* Informed consent in place for a randomized study of the Study Alliance Leukemia (SAL) including the Heidelberg Leukemia Network (HeLeNe) covering assessment of MRD by MPFC in the reference laboratories in Heidelberg and Dresden.

Exclusion Criteria:

* No signed informed consent compliant with the requirements of PERDAM

Primary outcomes:
measure: Correlation between Measurable Residual Disease (MRD) and Survival with respect to treatment effects
timeFrame: after 3 and 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
state: BW
Study officials:
affiliation: University Hospital Heidelberg
name: Richard F Schlenk, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: