Molecular Evaluation of AML Patients After Stem Cell Transplant to Understand Relapse Events

Study Overview
=================
Brief Summary
-----------------
Prospective determination of the clinical utility of measurable residual disease (MRD) testing for relapse and survival of patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (alloHCT).

Detailed Description
-----------------
This is a multi-center non-randomized prospective study designed to establish a national framework for introducing measurable residual disease testing into the clinical care of AML patients undergoing allogeneic transplantation. Enrollment is expected to occur over a 4-year period, with an additional 3 years of follow-up. Subject participation this study will be approximately 3 years. Up to 1,000 subjects will be enrolled. Subjects will be asked to provide blood samples at months 1-6, 9, 12, 15, and 18 post-transplant, and archived specimens from time of AML diagnosis and any bone marrow samples collected for clinical purposes will be requested for research testing. Additional blood and marrow samples will be requested at relapse (if applicable).

Official Title
-----------------
Molecular Evaluation of AML Patients After Stem Cell Transplant to Understand Relapse Events

Conditions
-----------------
Acute Myeloid Leukemia in Remission

Intervention / Treatment
-----------------
* Other: Prospective determination of the clinical utility of measurable residual disease (MRD) testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Aged at least 18 years old at time of consent Diagnosed with AML, in complete remission Complete remission (CR) definition per local institutional criteria CR with incomplete hematologic recovery (CRi) is not an exclusion criterion MRD positivity is not an exclusion criterion Undergoing alloHCT Has specimen from time of AML diagnosis available Exclusion Criteria: Diagnosis of acute promyelocytic leukemia Prior alloHCT

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult patients with AML in complete remission undergoing alloHCT<br>Adult patients with AML in complete remission undergoing alloHCT | Other: Prospective determination of the clinical utility of measurable residual disease (MRD) testing<br>* Prospective determination of the clinical utility of measurable residual disease (MRD) testing for relapse and survival of patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (alloHCT).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival post-alloHCT via comparison between those testing positive or negative using an optimized molecular monitoring approach. | Through up to 3 years post-alloHCT | 
| Cumulative incidence of relapse | Cumulative incidence of relapse post-alloHCT via comparison between those testing positive or negative using an optimized molecular monitoring approach. | Through up to 3 years post-alloHCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Prediction - Testing Approaches | Proportion of post-alloHCT relapses identified by different MRD testing approaches with optimal test thresholds at peri-transplant timepoints. | Through up to 3 years post-alloHCT | 
| Relapse Prediction - Pre-Transplant Testing | Proportion of post-alloHCT relapses predicted by pre-transplant testing (comparing blood with marrow when available). | Through up to 3 years post-alloHCT | 
| Relapse Prediction - Early Prediction | Proportion of post-alloHCT relapses identified one month or more earlier than local testing by post-alloHCT optimized monitoring. | Through up to 3 years post-alloHCT | 
| Relapse Prediction - Time to Relapse | Time from testing positive by optimized monitoring to relapse. | Through up to 3 years post-alloHCT | 
| Biology of Relapse - Change in Genetic Profile | for subjects with relapse sample available) - Proportion of relapses with change in genetic profile to diagnosis. | Through up to 3 years post-alloHCT | 
| Biology of Relapse - Change in Immunophenotype | (for subjects with relapse sample available) - Proportion of relapses with change in immunophenotype to diagnosis. | Through up to 3 years post-alloHCT | 
| Biology of Relapse - HLA Loss | (for subjects with relapse sample available) - Proportion of relapses with evidence of human leukocyte antigen (HLA) loss. | Through up to 3 years post-alloHCT |