Leukemia Stem Cell Detection in Acute Myeloid Leukemia

Study Overview
=================
Brief Summary
-----------------
Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) following induction chemotherapy. However, a large majority subsequently relapse and succumb to the disease. Currently, cytogenetics and molecular aberrations are the best prognostic indicators; however, these factors cannot prognosticate accurately for individual patients. Overall, the majority of patients with favorable or intermediate-risk AML will experience relapse. Prognosis after relapse is dismal with a five-year overall survival rate of less than 10%. A leukemia stem cell (LSC) paradigm may explain this failure of CR to reliably translate into cure. This study is undertaken to determine whether the presence of LSCs has prognostic value as well as to determine whether the presence of LSCs has predictive value. This study has an observational component, whereby we intent evaluate whether the presence or absence of LSCs is prognostic. This study also has an interventional component in which it uses LSC status to determine whether favorable and intermediate risk AML patients in CR receive consolidation with chemotherapy or allogeneic HCT.

Official Title
-----------------
Leukemia Stem Cell Detection in Acute Myeloid Leukemia

Conditions
-----------------
Acute Myeloid Leukemia (AML)

Intervention / Treatment
-----------------
* Procedure: Allogeneic HCT
* Drug: Consolidation chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must have previously signed the specimen procurement protocol consent associated with the leukemia stem cell assay (Step 1 informed consent) prior to starting AML therapy. Age 18 years and older New diagnosis of AML, other than APL, confirmed by bone marrow aspirate/biopsy and reviewed by an institutional hematopathologist Completion of induction therapy, as defined by the Investigator and post-induction bone marrow biopsy. Exclusion Criteria: Any debilitating medical or psychiatric illness that would preclude ability to follow study procedures. Indeterminate leukemia stem cell assay results at diagnosis.

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Evaluable Cohort - Transplant Arm<br>Other - Standard of Care Consolidation (HCT) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements: Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria) Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0) Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT); HMA-based induction subjects: Are candidates for (as determined by the investigator) and receive HCT | Procedure: Allogeneic HCT<br>* Allogeneic HCT<br>* Other names: transplant, allo HCT, PBSCT, SCT, BMT;|
| Other: Evaluable Cohort - Consolidation Chemo Arm<br>Other - Standard of Care Consolidation (cytarabine-based chemo) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements: Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria) Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0) Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT) | Drug: Consolidation chemotherapy<br>* Cytarabine-based consolidation chemotherapy<br>* Other names: cytarabine, HiDAc, high dose cytarabine;|
| No Intervention: Observational Cohort 1<br>Enrolled subjects who do not achieve a CR to induction therapy, regardless of diagnostic phenotype. Following completion of induction therapy and remission bone marrow aspirate, if a subject is determined to not have achieved a complete remission to induction therapy, he or she would be included in observational cohort 1. | |
| No Intervention: Observational Cohort 2<br>Enrolled subjects who achieve a CR to induction therapy but meet one or more of the following criteria: Lack the immunophenotype of interest, Cytarabine based induction subjects: Are not candidates for [as determined by the investigator (e.g. unfit or refusal)] and do not receive consolidation therapy (cytarabine-based chemotherapy or HCT) HMA-based induction subjects: Are not candidates for [as determined by the investigator (e.g. unfit, lack of donor, refusal)] and do not receive HCT Final investigator determination of fit-ness can occur at any time until the start of consolidation therapy. HMA-based induction subjects will not receive consolidation cytarabine-based chemotherapy as part of the evaluable cohort if they do not receive HCT. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 Year Relapse Free Survival (RFS) | Comparison of 2 year RFS in patient with detectable LSCs in the marrow at the end of consolidation to the 2 year RFS of patients without detectable LSCs. IWG Criteria (Cheson 2003) was utilized to classify relapse, with relapse defined as ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease, or disease presence determined by a physician upon clinical assessment. | 2 years |