UMIN-CTR Clinical Trial

Public title

Safety and efficacy of umbilical cord blood (UCB) transplantation using a low-dose total body irradiation (TBI) containing regimen for hematologic malignancies

Acronym

Safety and efficacy of umbilical cord blood (UCB) transplantation using a low-dose total body irradiation (TBI) containing regimen for hematologic malignancies

Scientific Title

Safety and efficacy of umbilical cord blood (UCB) transplantation using a low-dose total body irradiation (TBI) containing regimen for hematologic malignancies

Scientific Title:Acronym

Safety and efficacy of umbilical cord blood (UCB) transplantation using a low-dose total body irradiation (TBI) containing regimen for hematologic malignancies

Region

Japan

Condition

Hematologic malignancies with an indication for allogeneic hematopoietic stem cell transplantation

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the safety and efficacy of UCB transplantation following low-dose TBI containing reduced intensity conditioning for hematologic malignancy patients with advanced age or organ dysfunction, who lack a suitable related or unrelated donor, or who require urgent allogeneic hematopoietic stem cell transplantation.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Day 60 survival rate of patients with successful engraftment after transplantation

Key secondary outcomes

(1) Overall survival and progression free survival at day 100
(2) Non-relapse mortality at day 100
(3) Rate of primary graft failure, secondary graft failure
(4) Time to hematopoietic recovery and achievement of complete donor T-cell chimerism
(5) Incidence and severity of acute GVHD and chronic GVHD
(6) Regimen-related toxicity
(7) Rate of relapse
(8) Incidence of bacterial, fungal and viral infection
(9) Immune reconstitution 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 with fludarabine 25mg/m2 for 5 days, melphalan 40mg/m2 for 2 days and TBI at a dose of 2 Gy on day-1 are used.
GVHD prophylaxis consists of tacrolimus given at 0.03mg/kg/day as continuous intravenous infusion from day-1 and mycophenolate mofetil at 750mg orally given three times a day from day 0.
UCB unit with more than 2.5 x 10^7/kg of cryopreserved total nucleated cell dose, which is serologically matched for greater than 4 of 6 HLA antigens is used.

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 with hematologic malignancies who are incurable by conventional treatments and therefore have an indication for allo-HSCT
Eligible diseases;
(a)AML
1. First CR with high risk
2. Second CR or greater
3. Relapse or failure to achieve CR by the first induction chemotherapy
(b)MDS
1. Poor prognosis MDS with IPSS scores of int-2 or higher
2. Patinets with transfusion-dependent MDS who require RBC transfusion over 2 units per week or platelet transfusion over 10 units per week
(c)CML
1. Second CP or greater
2. First CP or tyrosine kinase inhibitor failure
(d)Malignant lymphoma
1. Indolent lymphoma (including CLL)
First relapse/progression,or greater, regardless of sensitivity to prior chemotherapy
(e)ALL (including Ph positive ALL)
1. CR
(2) Patients lacking a 5/6 or 6/6 HLA-A/B/DR serologically matched related donor
(3) Patients lacking an HLA-A/B/DR serologically matched unrelated donor, patients who require urgent transplantation due to disease status but can hardly receive transplantation from unrelated HLA-matched donor in a timely fashion
(4) ECOG performance status score: 0-2
(5) Patients who are not candidates for myeloablative transplantation
(6) Written informed consent before participation

Key exclusion criteria

(1)Patients who have any major organ dysfunction as follow
(a) Heart: Ejection fraction <30% at rest
(b) Lung: %VC<30% or FEV1.0%<40% or PaO2<60mmHg(SpO2<90%) on room air
(c) Kidney: serum creatinine level >2.0 mg/dl
(d) Liver: total bilirubin level >2.0 mg/dl or ALT>3.0 x ULN (upper limit of normal) or chronic active hepatitis or cirrhosis
(2) Poorly controlled hypertention
(3) Positivity for HIV antibody
(4) Uncontrolled active infections
(5) Uncontrolled central nervous system involvement
(6) Pregnant, nursing or possibly pregnant woman
(7) Patients with mental disorder who are considered difficult to participate in the study
(8) Known hypersensitivity to any of the drugs in the conditioning regimen or drugs used for GVHD prophylaxis
(9) Patients with positive donor-specific HLA antibodies(DSA)
(10) Engraftment failure after allogeneic hematopoietic stem cell transplantation
(11) Inappropriate to participate in this study as judged by the physician in charge

Target sample size

7

Name of lead principal investigator

1st name
Middle name
Last name	Masayuki Hino

Organization

Osaka City University, Graduate School of Medicine

Division name

Hematology

Zip code

Address

1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585

TEL

06-6645-3881

Email

hinom@med.osaka-cu.ac.jp

Name of contact person

1st name
Middle name
Last name	Mika Nakamae

Organization

Osaka City University, Graduate School of Medicine

Division name

Hematology(Clinical research center for hematological malignancies )

Zip code

Address

1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585

TEL

06-6645-3881

Homepage URL

Email

crc-hematology@med.osaka-cu.ac.jp

Institute

Hematology, Osaka City University, Graduate School of Meicine

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

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

Date of disclosure of the study information

2010

Year

10

Month

06

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

Terminated

Date of protocol fixation

2010

Year

09

Month

30

Day

Date of IRB

Anticipated trial start date

2010

Year

10

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

10

Month

06

Day

Last modified on

2016

Year

10

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004968