Allogeneic HCT Using Uniform Conditioning Regimen Regardless of Donors (MS, MU, or HF) for AML in Remission (AML_AlloHCT)

Allogeneic HCT From Donor-sources of Matched-sibling, Matched-unrelated, or Haploidentical-family Donors Using Uniform Conditioning Regimen of Busulfan, Fludarabine, and Antithymocyte Globulin for AML in Remission - an Observational Study

The purpose of this study is to evaluate the effect of various clinical variables including HLA-disparity and NK cell-related variables, upon outcomes of allogeneic hematopoietic cell transplantation (HCT) using uniform conditioning regimen including busulfan, fludarabine, and antithymocyte globulin (ATG) in patients with acute myeloid leukemia (AML) in the first complete remission (CR). The donors for allogeneic HCT include HLA-matched siblings, matched unrelated donors, and haploidentical family donors.

Therefore, the endpoints of the study are engraftment, secondary graft failure, acute and chronic graft-versus-host disease (GVHD), immune recovery, infections, leukemia recurrence, non-relapse mortality, and relapse-free (RFS) and overall survival (OS) of patients.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Procedure: allogeneic hematopoietic cell transplantation

• Study Type: Observational
• Enrollment (Anticipated): 110

Contacts and Locations

• Study Contact: Name: Kyoo-Hyung Lee, MD; Phone Number: 82-2-3010-3213; Email: khlee2@amc.seoul.kr
• Study Contact Backup: Name: Seunghyun Baek, RN; Phone Number: 82-2-3010-7289; Email: bsh5932@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Kyoo-Hyung Lee, MD; Phone Number: 82-2-3010-3213; Email: khlee2@amc.seoul.kr
    • Contact: Inpyo Choi, PhD; Phone Number: 82-42-860-4223; Email: ipchoi@kribb.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a single center, observational study in a patient population with non-promyelocytic AML who have achieved complete remission after induction chemotherapy. The patients will be enrolled consecutively.

Description

Inclusion Criteria:

• Patients with non-promyelocytic AML (intermediate-risk or high-risk diseases by NCCN guideline 2016) in the first CR
• Patients should be 16 years of age or more and 75 years of age or less
• The performance status of the patients should be 70 or over by Karnofsky performance scale
• Patients should have adequate hepatic function (bilirubin less than 2.0 mg/dl, AST less than three times the upper normal limit)
• Patients should have adequate renal function (creatinine less than 2.0 mg/dl)
• Patients should have adequate cardiac function (ejection fraction > 40% on MUGA scan)
• Patients and stem cell donors must sign informed consent
• For hematopoietic cell donor, if a patient has an HLA-matched sibling (65 years or younger), that sibling will be a cell donor. If a patient does not have an HLA-matched sibling but an HLA-A, B, C, DRB1 7-8/8 matched unrelated donor, the unrelated donor will be a cell donor. If a patient has neither HLA-matched sibling nor unrelated donor, an HLA-haploidentical familial donor will be a cell donor.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
leukemia recurrence	reappearance of blast >5% in bone marrow; reappearance of leukemia blast in extramedullary sites	from HCT (day of donor cell infusion) to leukemia recurrence at 2 years after HCT
engraftment	recovery of absolute neutrophil count over >500/uL	from HCT to neutrophil count over >500/uL at 30 days after HCT
GVHD, acute and chronic	occurrence of acute or chronic GVHD after HCT	from HCT to the occurrence of GVHD at 2 years after HCT
Non-relapse mortality	occurrence of death without leukemia recurrence	from HCT to the occurrence of death without leukemia recurrence at 2 years after HCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse free survival	survival without leukemia recurrence/death	from HCT to last the follow-up, leukemia recurrence, or death at 2 years after HCT
overall survival	survival regardless of leukemia recurrence	from HCT to the last follow-up or death at 2 years after HCT

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Korea Research Institute of Bioscience & Biotechnology
• Investigators: Principal Investigator: Kyoo-Hyung Lee, MD, University of Ulsan, Asan Medical Center

Publications and helpful links

General Publications

• Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Hwang HJ, Jung AR, Kim SH, Yun SC, Shin HJ. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011 Sep 1;118(9):2609-17. doi: 10.1182/blood-2011-02-339838. Epub 2011 Jun 28.
• Lee KH, Lee JH, Lee JH, Kim DY, Park HS, Choi EJ, Ko SH, Seol M, Lee YS, Kang YA, Jeon M, Baek S, Kang YL, Kim SH, Yun SC, Kim H, Jo JC, Choi Y, Joo YD, Lim SN. Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission. Biol Blood Marrow Transplant. 2017 Sep;23(9):1555-1566. doi: 10.1016/j.bbmt.2017.05.025. Epub 2017 May 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2017
• Primary Completion (ANTICIPATED): March 30, 2021
• Study Completion (ANTICIPATED): March 30, 2021

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (ACTUAL): November 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 5, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: allogeneic hematopoietic cell transplantation; fludarabine; busulfan; ATG; AML CR
• Other Study ID Numbers: 2017-0204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No