UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Safety and efficacy of umbilical cord blood (UCB) transplantation using a low-dose total body irradiation (TBI) containing regimen for hematologic malignancies
Title of the study (Brief title)	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
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

Objectives
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

Assessment
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

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 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

Eligibility
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

Research contact person
Name of lead principal investigator	Masayuki Hino
Organization	Osaka City University, Graduate School of Medicine
Division name	Hematology
Address	1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585
TEL	06-6645-3881
Email	hinom@med.osaka-cu.ac.jp

Public contact
Name of contact person	Mika Nakamae
Organization	Osaka City University, Graduate School of Medicine
Division name	Hematology(Clinical research center for hematological malignancies )
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

Sponsor
Institute	Hematology, Osaka City University, Graduate School of Meicine
Institute
Department

Funding Source
Organization	none
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

Other administrative information
Date of disclosure of the study information	2010 Year 10 Month 06 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2010 Year 09 Month 30 Day
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

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Publication of results	Unpublished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

Management information
Registered date	2010 Year 10 Month 06 Day
Last modified on	2016 Year 10 Month 05 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004968