UMIN-CTR Clinical Trial

Public title

Multicenter clinical trial of reduced-intensity conditioning regimen for unrelated bone marrow transplantation with fludarabine, iv busulfan, and low-dose ATG-F

Acronym

U-RIST ATG protocol

Scientific Title

Multicenter clinical trial of reduced-intensity conditioning regimen for unrelated bone marrow transplantation with fludarabine, iv busulfan, and low-dose ATG-F

Scientific Title:Acronym

U-RIST ATG protocol

Region

Japan

Condition

Hematologic malignancy

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To test feasibility and efficacy of reduced-intensity conditioning regimen for unrelated bone marrow transplantation with fludarabine, iv busulfan, and low-dose ATG-F.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Day 100 survival with donor cell engraftment

Key secondary outcomes

1-year OS and PFS
1-year non-relapse mortality
Primary and secondary graft failure
Time to neutrophil engraftment and complete chimerism
Acute and chronic GVHD
Regimen-related toxicity (CTCAE ver 3.0)
Relapse or progression
Bacterial, fungal, and viral infection
Immune reconstitution

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

(1) Fludarabine, 30 mg/m2/day, div, on days -8 to -3
(2) Busulfan, 3.2 mg/kg/day div, divided into 4 doses, on days -6 and -5
(3) Anti-T-lymphocyte immunoglobulin (ATG-Fresenius), 5 mg/kg/day div, on day -2

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

65

years-old

>=

Gender

Male and Female

Key inclusion criteria

(1) Hematologic malignancy
(a) Acute myeloid leukemia
High risk CR1
CR2 or later CR
Relapse or primary refractory*
*who do not require chemotherapy for 1 month

(b) Myelodysplastic syndrome
IPSS intermediate-2 or high
Require blood transfusion of 10 units/week platelet or 2 units/week red blood cell
*Patients who have not received standard chemotherapy are ineligible.

(c) Chronic myeloid leukemia
CP2 or later CP
CP1 with gleevec failure
*Patients who have not received standard chemotherapy are ineligible.

(d) Malignant lymphoma
1. Indolent lymphoma including chronic lymphocytic leukemia
*First or later relapse/progression.
2. Aggressive lymphoma or Hodgkin lymphoma
*First or later relapse/progression with sensitivity to prior chemotherapy.

(2) No available HLA 6/6 matched or 5/6 matched related donor.

(3) Available HLA 8/8, 7/8, or 6/8 allele-matched unrelated donor

(4) Age at transplantation: between 16 years and 65 years

(5) ECOG performance status: 0 or 1

(6) Ineligible for myeloablative conditioning due to (A) older age (50 years or older), (B) organ dysfunction as mentioned below, or (C) a history of high-dose chemotherapy or total-body irradiation followed by autologous hematopoietic stem cell transplantation within 6 months.
(a) EF 40%-50%
(b) %VC 30%-40%, FEV1.0% 40%-50%, or PaO2 60-80 mmHg or SO2 90-95% on room air
(c) Serum Cr 1.5-2.0 mg/dl or above
(d) Serum bilirubin 1.5-2.0 mg/dl or ALT(GPT) 2-3xUNL

(7) Obtained informed consent from patients

(8) Expected to live at least 3 months after transplantation

Key exclusion criteria

(1) Patients with organ dysfunction as defined below are excluded.
(a) EF <40%
(b) %VC <30%, FEV1.0% <40%, or PaO2 <50 mmHg or SO2 <90% on room air
(c) Serum Cr 2.0 mg/dl or above
(d) Serum bilirubin >2.0 mg/dl, ALT(GPT) >3xUNL, chronic active hepatitis, or liver cirrhosis.

(2) Uncontrollable hypertension

(3) Positive anti-HIV antibody

(4) Uncontrollable active infection

(5) Uncontrollable CNS disease

(6) During pregnancy or breast-feeding

(7) Patients with severe psychiatric problems

(8) Allergy to drugs for conditioning and GVHD prophylaxis

(9) Patients who are considered as ineligible by attending physicians

Target sample size

27

Name of lead principal investigator

1st name
Middle name
Last name	Fukuda, Takahiro

Organization

National Cancer Center Hospital

Division name

Hematopoietic Stem Cell Transplantation Division

Zip code

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan

TEL

03-3542-2511

Email

Name of contact person

1st name
Middle name
Last name	Fukuda, Takahiro

Organization

National Cancer Center Hospital

Division name

Hematopoietic Stem Cell Transplantation Division

Zip code

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan

TEL

03-3542-2511

Homepage URL

Email

Institute

National Cancer Center Hospital

Institute

Department

Personal name

Organization

Grants from the Japanese Ministry of Health, Labor and Welfare

Organization

Division

Category of Funding Organization

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）
東京慈恵会医科大学附属病院（東京都）
横浜市立大学附属病院（神奈川県）
国立病院機構熊本医療センター（熊本県）
大阪市立大学医学部附属病院（大阪府）
三重大学医学部附属病院（三重県）
信州大学医学部附属病院（長野県）
国際医療センター戸山病院（東京都）
東京都立駒込病院（東京都）
金沢大学附属病院（石川県）
和歌山県立医科大学（和歌山県）

Date of disclosure of the study information

2010

Year

12

Month

08

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

Open public recruiting

Date of protocol fixation

2008

Year

03

Month

18

Day

Date of IRB

Anticipated trial start date

2009

Year

01

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2010

Year

12

Month

08

Day

Last modified on

2010

Year

12

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005573