UMIN-CTR Clinical Trial

Public title

Phase II study of allogeneic hematopoietic stem cell transplantation for patients with myeloid malignancies using once daily intravenous busulfan and fludarabine as conditioning regimen

Acronym

IVBU1002(FB4): Phase II study of once daily ivBu+Flu

Scientific Title

Phase II study of allogeneic hematopoietic stem cell transplantation for patients with myeloid malignancies using once daily intravenous busulfan and fludarabine as conditioning regimen

Scientific Title:Acronym

IVBU1002(FB4): Phase II study of once daily ivBu+Flu

Region

Japan

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

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

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

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Takuya Yamashita

Organization

National Cancer Center Hospital

Division name

Hematopoietic Stem Cell Transplantation Division

Zip code

Address

5-1-1, Tsukiji, Chuo, Tokyo

TEL

+81-3-3542-2511

Email

tayamash@ncc.go.jp

Name of contact person

1st name
Middle name
Last name	Takuya Yamashita

Organization

National Cancer Center Hospital

Division name

Hematopoietic Stem Cell Transplantation Division

Zip code

Address

5-1-1, Tsukiji, Chuo, Tokyo

TEL

+81-3-3542-2511

Homepage URL

Email

tayamash@ncc.go.jp

Institute

Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital

Institute

Department

Personal name

Organization

The Ministry of Health, Labor and Welfare

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立がん研究センター中央病院（東京都）

Date of disclosure of the study information

2013

Year

01

Month

21

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2012

Year

10

Month

09

Day

Date of IRB

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

Other related information

Registered date

2013

Year

01

Month

12

Day

Last modified on

2018

Year

10

Month

31

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011442