Evaluation of Measurable Residual Disease in Patients With Acute Myeloid Leukemia as Surrogate Endpoint for Survival (PERDAM)

Prospective Evaluation of Measurable Residual Disease in Intensively Treated Patients With Acute Myeloid Leukemia (AML) as Surrogate Endpoint for Survival

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

Study Overview

• Status: Terminated
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Other: Measurable residual disease measured by flow cytometry

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.

• Study Type: Observational
• Enrollment (Actual): 51

Contacts and Locations

Study Locations

• Germany
  • BW
    • Heidelberg, BW, Germany, 69124
      • University Hospital Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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)

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between Measurable Residual Disease (MRD) and Survival with respect to treatment effects	MRD will be assessed using multiparameter flow cytometry early (after induction / salvage). Survival will be assessed continuously. After 3 and 6 years correlation between MRD and survival will be analysed with respect to treatment effects to assess if MRD may serve as surrogate endpoint. If levels of MRD measured early during treatment are closely related to overall survival and thus may serve as an early surrogate will be assessed yearly.	after 3 and 6 years

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Collaborators: German Cancer Research Center; University Hospital Dresden
• Investigators: Principal Investigator: Richard F Schlenk, Prof. Dr., University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2019
• Primary Completion (ACTUAL): September 11, 2022
• Study Completion (ACTUAL): September 11, 2022

Study Registration Dates

• First Submitted: May 7, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (ACTUAL): June 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Leukemia, Myeloid, Acute; measurable residual disease; surrogate endpoint; multiparameter flow cytometry
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm, Residual
• Other Study ID Numbers: NCT-2018-0554

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No