UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase II study of allogeneic hematopoietic stem cell transplantation for patients with myeloid malignancies using once daily intravenous busulfan and fludarabine as conditioning regimen
Title of the study (Brief title)	IVBU1002(FB4): Phase II study of once daily ivBu+Flu
Region	Japan

Condition
Condition	acute myeloid leukemia(AML) myelodysplastic syndrome(MDS) chronic myelogenous leukemia(CML)
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To investigate safety and efficacy of allogeneic hematopoietic stem cell transplantation using once daily intravenous busulfan(ivBu) and fludarabine phosphate(Flu) as conditioning regimen for patients with AML, MDS and CML
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Probability of event-free survival at 1 year after transplantation
Key secondary outcomes	(1) Incidence of Bearman's grade 2 or higher adverse events which occur from the begining of conditioning regimen to 28 days after transplantation (2) Cumulative incidence of engraftment at 100 days after transplantation (3) Cumulative incidence of non-relapse mortality at 100 days after transplantation (4) Cumulative incidence of SOS(sinusoidal obstrction syndrome) at 100 days after transplantation (5) Cumulative incidence of grade II-IV acute GVHD at 1 year after transplantation (6) Cumulative incidence of chronic GVHD at 1 year after transplantation (7) Probability of overall survival and cumulative incidence of relapse at 1 year after transplantation

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Conditioning regimen Intravenous busulfan 3.2mg/kg/day x 4days + Fludarabine phosphate 30mg/m^2/day x 6days
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	16 years-old <=
Age-upper limit	70 years-old >
Gender	Male and Female
Key inclusion criteria	(1) Patients between the age of 16 and 70 at informed consent (2) Patients diagnosed as AML, MDS, CML who are eigible for allogeneic hematopoietic stem cell transplantation. No limitation of disease status at transplantation. Patients who need chemotherapy for disease control except imatinib, dasatinib and nilotinib for CML are excluded (3) Patients who have the fixed schedule about the harvest of bone marrow or paripheral blood stem cells from related or unrelated donors who meet the following conditions: 1) HLA-A, B, DRB1 are genetically identical 2) HLA-A and B are genetically identical and 1 locus of HLA-DRB1 is genetically mismatched (4) Patients whose performance status are 0 or 1 by ECOG criteria (5) Patients who do not meet the application of myeloablative conditioning such as ivBu+Cy. These patients meet the either conditions (A) age or (B) organ dysfunction (A) Patients fifty and over at registration (B) Patients who meet at least one of the following conditions about organ dysfunction 1) SPO2>=90% and =<94% by room air, %VC>=30% and =<80% or FEV1.0%>=40% and =<70% 2) sCr>=1.5 and =<2.0mg/dL 3) T-bil>=1.5 and =<2.0mg/dL 4) AST, ALT or ganma-GTP>=2 x and =<3 x upper limit of normal range 5) Ejection fraction of left ventricle>=40% and =<50% by UCG (6) Patients who give written informed consent following sufficient explanation. Patients who are under 20 years old are required to give informed consent from both persons with parental authority and patients themselves
Key exclusion criteria	(1) Patients who have one of the following organ dysfunction 1) SPO2<90% by room air, %VC=<30% or FEV1.0%=<40% 2) sCr>2.0mg/dL 3) T-bil>2.0mg/dL 4) AST, ALT or ganma-GTP>3 x upper limit of normal range 5) Ejection fraction of left ventricle<40% by UCG (2) Patients with uncontrolled diabetes mellitus in spite of regular use of insulin (3) Patients with uncontrolled hypertension in spite of use of antihypertensive drugs (4) Patients who have active infection (5) Patients who are positive for TPHA, HBV surface antigen or anti-HCV antibody (6) Patients who are positive for anti-HTLV-I or anti-HIV antibody (7) Patients who are not evaluated to be able to survive more than 100 days after transplantation (8) Patients who have coinciding active malignancies (9) Patients who are pregnant or in the lactation period, and who are not able to, or not willing to prevent conception during the therapeutic period of this clinical trial (10) Patients who have psychiatric disorder (11) Patients who have prior hematopoietic stem cell transplantation (12) Patients who are considered as inappropriate to register by attending physicians
Target sample size	75

Research contact person
Name of lead principal investigator	Takuya Yamashita
Organization	National Cancer Center Hospital
Division name	Hematopoietic Stem Cell Transplantation Division
Address	5-1-1, Tsukiji, Chuo, Tokyo
TEL	+81-3-3542-2511
Email	tayamash@ncc.go.jp

Public contact
Name of contact person	Takuya Yamashita
Organization	National Cancer Center Hospital
Division name	Hematopoietic Stem Cell Transplantation Division
Address	5-1-1, Tsukiji, Chuo, Tokyo
TEL	+81-3-3542-2511
Homepage URL
Email	tayamash@ncc.go.jp

Sponsor
Institute	Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital
Institute
Department

Funding Source
Organization	The Ministry of Health, Labor and Welfare
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	国立がん研究センター中央病院（東京都）

Other administrative information
Date of disclosure of the study information	2013 Year 01 Month 21 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 10 Month 09 Day
Anticipated trial start date	2013 Year 01 Month 21 Day
Last follow-up date	2015 Year 04 Month 30 Day
Date of closure to data entry	2018 Year 03 Month 31 Day
Date trial data considered complete	2018 Year 03 Month 31 Day
Date analysis concluded	2019 Year 03 Month 31 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2013 Year 01 Month 12 Day
Last modified on	2018 Year 10 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011442