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

Phase 2

Withdrawn

• Conditions: Acute Myeloid Leukemia; Minimal Residual Disease Negativity
• Interventions: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Etoposide; Other: Laboratory Biomarker Analysis

• Registration Number: NCT03515707
• Lead Sponsor: Fred Hutchinson Cancer Center

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.

Study Timeline

• Study First Submitted: 2018-04-23
• Study First Submitted QC: 2018-04-23
• Study First Posted: 2018-05-03
• Study Start: 2018-07-10
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-27
• Last Update Posted: 2021-02-01
• Primary Completion: 2022-04-15
• Study Completion: 2022-07-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (busulfan, etoposide, ASCT)	Autologous Hematopoietic Stem Cell Transplantation	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.
Treatment (busulfan, etoposide, ASCT)	Laboratory Biomarker Analysis	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.
Treatment (busulfan, etoposide, ASCT)	Busulfan	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.
Treatment (busulfan, etoposide, ASCT)	Etoposide	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States