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

Leukemia, Myeloid, Acute Clinical Trial

— PERDAM  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03549351
• Other study ID #: NCT-2018-0554
• Status: Terminated
• Start date: June 1, 2019
• Est. completion date: September 11, 2022

Study information

• Verified date: September 2022
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 51
• Est. completion date: September 11, 2022
• Est. primary completion date: September 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasm, Residual

Intervention

Other:
• Measurable residual disease measured by flow cytometry
Measurable residual disease measured by flow cytometry

Locations

Country	Name	City	State
Germany	University Hospital Heidelberg	Heidelberg	BW

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Heidelberg	German Cancer Research Center, University Hospital Dresden

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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