UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Hematopoietic stem cell transplantation from HLA fully mismatched family members for post-transplant relapse/rejection (phase I/II trial)
Title of the study (Brief title)	HLA fully mismatched hematopietic stem cell transplantation
Region	Japan

Condition
Condition	hematologic malignancies relapesd/rejected after allogeneic 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 stem cell transplantation from HLA fully mismatched family members for hematologic malignancies relapsed or rejected after allogeneic transplantation
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase I,II

Assessment
Primary outcomes	Rate of donor cell engraftment (defined as Neutrophil >500/microL with >90% of donor origin) on day 35
Key secondary outcomes	a) Incidence and severity of chronic GVHD b) transplantion-associated complications, including TMA c) survival rate d) relapse rate e) other adverse effects (CTCAE) within three months

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The basic structure of the preconditioning regimen consists of fludarabine (FLU) at 30 mg/m2/day for 6 days (days -9 and -4), melphalan (MEL) at 70 mg/ m2/day for 2 days (days -3 and -2), and rabbit anti-thymocyte globulin (ATG, Thymoglobulin, Sanofi) at 1.25 mg/kg/day for 2 days (days -2 and -1). To ensure engraftment, 3 Gy of total body irradiation (TBI) was added. For active diseases, high-dose cytarabine (CA) at 2 g/m2/day for 4 days (days -9 and -6) was added for the purpose of tumor reduction. To prevent anaphylaxis caused by ATG, methylprednisolone (mPSL) was administered at 2 mg/kg on days -2 and -1. GVHD prophylaxis consists of the continuous infusion of TAC with a target concentration of 10-12 ng/mL started from day -3, 1 mg/kg/day of mPSL started after day 0, and 15 mg/kg/day of MMF started from day 3 (Table 1). Peripheral blood stem cells (PBSC) were used as a stem cell source, which were infused without being frozen. G-CSF was administered from day 3 to the day of engraftment.
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	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients with hematologic malignancies relapsed or rejected after allogeneic stem cell transplantation who fulfill the following (patient and donor), [patient] 1) Written informed consent 2) no expectancy of cure with standard therapies including DLI [donor] 1) healthy spouse who desires to become the donor 2) no available or suitable donor in unrelate bank, cord blood bank, haploidentical relatives (confirmed by the conference)
Key exclusion criteria	1) Cre > 2.0 mg/dl 2) EF < 40% 3) T-Bil > 2.0 mg/dl 4) AST and/or ALT > 200 U/L 5) SpO2 < 90% (room air) 6) PS (ECOG score) 3-4 Patients with data due to original disease are not excluded.
Target sample size	20

Research contact person
Name of lead principal investigator	Hiroyasu Ogawa
Organization	Hyogo College of Medicine
Division name	Division of Hematology, Department of Internal Medicine
Address	1-1, Mukogawa-cho, Nishinomiya city, Hyogo
TEL	+81-798-45-6886
Email	haplo@hyo-med.a.cjp

Public contact
Name of contact person	Kazuhiro Ikegame
Organization	Hyogo College of Medicine
Division name	Division of Hematology, Department of Internal Medicine
Address	1-1, Mukogawa-cho, Nishinomiya city, Hyogo
TEL	+81-798-45-6886
Homepage URL
Email	kame@hyo-med.ac.jp

Sponsor
Institute	Hyogo College of Medicine
Institute
Department

Funding Source
Organization	Ministry of Education, Culture, Science and Technology
Organization
Division
Category of Funding Organization	Japanese Governmental office
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	2016 Year 08 Month 09 Day

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2016 Year 08 Month 08 Day
Anticipated trial start date	2016 Year 08 Month 09 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	2016 Year 08 Month 08 Day
Last modified on	2017 Year 02 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027122