Acute Myeloid Leukemia, Minimal Residual Disease Negativity
Conditions
Brief summary
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
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.
Interventions
PROCEDUREAutologous Hematopoietic Stem Cell Transplantation
Undergo ASCT
DRUGBusulfan
Given IV or oral
DRUGEtoposide
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment related mortality | From first dose of study therapy to day +100 | Number of deaths without a prior relapse (unrelated to disease) |
| Relapse | Assessed up to 2 years post autologous stem cell transplant (ASCT) | Proportion of patients who relapse, as defined by 2017 National Comprehensive Cancer Network (NCCN ) Acute Myeloid Leukemia (AML) guidelines. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival | Assessed up to 4 years post-ASCT | Proportion of patients living without relapse |
| Overall survival | Assessed up to 4 years post-ASCT | Proportion of patients living with or without relapse |
Countries
United States
Outcome results
None listed