Stem Cell Transplant to Treat Patients With Favorable or Intermediate Risk Minimal Residual Disease Negative Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This phase II trial studies how well autologous stem cell transplant works in treating patients with favorable or intermediate risk, minimal residual disease (MRD)-negative, acute myeloid leukemia. Giving chemotherapy before a peripheral blood stem cell transplant helps kill any cancer cells that are in the body. After treatment, stem cells are collected from the patient's blood and stored. Higher dose chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the estimated probability of relapse at 2 years after autologous peripheral blood stem cell (PBSC) transplant. SECONDARY OBJECTIVES: I. Estimate the probability of transplant-related mortality (TRM) at 100 days following autologous stem cell transplant (ASCT). II. Estimate probabilities of overall and disease-free survival. III. Assess if biological and molecular correlative studies can predict better outcome. OUTLINE: Patients receive targeted busulfan intravenously (IV) or oral (PO) every 6 hours on days -7 to -4 and etoposide IV on day -3. Patients then undergo autologous stem cell transplant on day 0. After completion of study treatment, patients are followed up yearly for 2 years.

Official Title
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Autologous Transplant as Treatment for Favorable or Intermediate Risk MRD-Negative AML Patients After Initial Induction Therapy

Conditions
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Acute Myeloid Leukemia, Minimal Residual Disease Negativity

Intervention / Treatment
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* Procedure: Autologous Hematopoietic Stem Cell Transplantation
* Drug: Busulfan
* Drug: Etoposide
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AML favorable or intermediate ELN risk Achieved true 1st complete response (CR) (absolute neutrophil count [ANC] and platelet count > 1,000/ul and 100,000/ul respectively) after first cycle of induction therapy, with no minimal residual disease (MRD) No measurable residual disease (MRD) as assessed by flow cytometry after initial induction therapy Performance score Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 Creatinine < 2.0 mg/dl and calculated by Cockcroft-Gault (CG) formula or 24 hour measured creatinine clearance (CRCL) > 50 Not pregnant Received 1-2 courses of post remission consolidation therapy prior to mobilization PBSC No MRD by flow, cytogenetics, fluorescence in situ hybridization (FISH) and molecular testing prior to collection of autologous PBSC collection Plan is to collect at least 3 x 10^6 CD34+ PBSC/kg cryopreserved; preference is 4-5 X 10^6 CD34 cells/kg Exclusion Criteria: Life expectancy is severely limited by diseases other than AML Total bilirubin > 2.0 mg/dl or serum glutamic-oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) > 2.5 x upper limit of normal (ULN) History of Gilbert's disease Uncontrolled arrhythmias, left ventricular ejection fraction (LVEF) < 50% or corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 50% Significant active infection that precludes transplant Hepatitis B or C viremia at time of ASCT History of central nervous system (CNS) involvement with AML

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (busulfan, etoposide, ASCT)<br>Patients receive busulfan IV or oral every 6 hours on days -7 to -4 and etoposide IV on day -3. Patients then undergo autologous stem cell transplant on day 0. | Procedure: Autologous Hematopoietic Stem Cell Transplantation<br>* Undergo ASCT<br>* Other names: Autologous Stem Cell Transplantation;Drug: Busulfan<br>* Given IV or oral<br>* Other names: WR-19508;Drug: Etoposide<br>* Given IV<br>* Other names: VP-16-213;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse | Proportion of patients who relapse, as defined by 2017 National Comprehensive Cancer Network (NCCN ) Acute Myeloid Leukemia (AML) guidelines. | Assessed up to 2 years post autologous stem cell transplant (ASCT) | 
| Treatment related mortality | Number of deaths without a prior relapse (unrelated to disease) | From first dose of study therapy to day +100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Proportion of patients living without relapse | Assessed up to 4 years post-ASCT | 
| Overall survival | Proportion of patients living with or without relapse | Assessed up to 4 years post-ASCT |