UMIN-CTR Clinical Trial

Basic information
Public title	Hematopoietic stem cell transplantation from a related donor with HLA-1 Ag mismatch in the graft-versus-host direction using anti-thymocyte globulin as a GVHD prophylaxis: multicenter phase II trial.
Acronym	HSCT from a related donor with HLA-1 Ag mismatch using ATG
Scientific Title	Hematopoietic stem cell transplantation from a related donor with HLA-1 Ag mismatch in the graft-versus-host direction using anti-thymocyte globulin as a GVHD prophylaxis: multicenter phase II trial.
Scientific Title:Acronym	HSCT from a related donor with HLA-1 Ag mismatch using ATG
Region	Japan

Condition
Condition	Acute myeloid leukemia Acute lymphoblastic leukemia Adult T cell leukemia Chronic myelogenous leukemia Myelodysplastic syndrome Non-Hodgkin lymphoma Hodgkin lymphoma
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To assess the efficacy and the safety of hematopoietic stem cell transplantation from a related donor with HLA-1 Ag mismatch in the GVH direction using ATG as a GVHD prophylaxis
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Success rate at 1 year after transplantation. (Success is defined as the situation without the following events within 1 year after transplantation. 1. Death 2. Relapse 3. Grades 3-4 acute GVHD 4. Severe chronic GVHD (NIH criteria))
Key secondary outcomes

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	Prophylaxis against GVHD is performed with tacrolimus, methotrexate, and thymoglobulin (anti-thymocyte globulin). Tacrolimus is started on day -1 at a dose of 0.03 mg/kg per day by continuous infusion, and the dose is adjusted to maintain a blood concentration between 12 and 15 ng/mL. Methotrexate is administered at 10 mg/m2 on day 1 and 7 mg/m2 on days 3 and 6. For patients with non-infectious fever on day 11 or before, methotrexate may be administered at 7 mg/m2 on day 11. Thymoglobulin is administered at 1.25 mg/kg per day on day-4 and day-3.
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	65 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Patients who have one of the following disease statuses (a) AML:any stages with <=50% of blasts in BM and PB (b) ALL:any stages with <=50% of blasts in BM and PB (c) ATL:any stages with <=50% of malignant cells in BM and PB (d) CML:stages with either >=CP2, AP, BP, or failure to 2 types of TKIs (imatinib, dasatinib, nilotinib), with <=50% of blasts in BM and PB (e) MDS:IPSS, intermediate-II or high; WPSS, intermediate-II or high; relapse after remission (f) NHL:patients who have one of the following statuses (1) low-grade lymphoma:chemo-refractory, relapse after autologous SCT (2) intermediate-grade lymphoma:PR,>=CR2 (3) high-grade lymphoma:PR, CR (g) Hodgkin lymphoma:PR, >=CR2 2. Patients who are 16 to 65 years old 3. Patients who do not have an available HLA-A, -B, -DR matched related donor 4. Patients who do not have an HLA-A, -B, -C, -DRB1 8/8 allele matched unrelated donor candidate, or patients whose disease status preclude time-consuming donor coordination. 5. Patients who have a donor with an HLA-1 Ag mismatch in the GVH direction 6. Donors who are 16 to 65 years old 7. Patients with ECOG performance status of 0, 1, or 2 8. Patients whose major organ functions (heart, lung, liver, kidney) are preserved and who meet all of the following criteria (a) Ejection fraction>=40% (b) SaO2>=94% on room air or SpO2>=94% on room air (c) Pulmonary function test: %VC>=70%, FEV1.0%>=70% (d) Serum total bilirubin <=2.0 mg/dl and serum AST<=5 x ULN (e) Ccr >=30ml/min
Key exclusion criteria	1. Patients with positive donor-specific HLA antibodies 2. Patients with HBs antibody positive 3. Patients with HIV antibody positive 4. Patients with serious mental disorder who are likely unable to participate in the study 5. Patients who are pregnant, nursing, or possibly pregnant 6. Patients with coexistence of malignancy 7. Patients with poorly controlled active infection 8. Patients who are allergic to ATG 9. Patients who have a history of receiving allogeneic stem cell transplantation once or more or a history of receiving autologous stem cell transplantation twice or more
Target sample size	39

Research contact person
Name of lead principal investigator	1st name Yoshinobu Middle name Last name Kanda
Organization	Saitama Medical Center, Jichi Medical University
Division name	Division of Hematology
Zip code	330-8503
Address	1-847 Amanuma-cho, Omiya-ku, Saitama City, Saitama 330-8503, Japan
TEL	048-647-2111
Email	ycanda-tky@umin.ac.jp

Public contact
Name of contact person	1st name Junya Middle name Last name Kanda
Organization	Kyoto University Hospital
Division name	Department of Hematology
Zip code	606-8507
Address	Sakyo-ku, Kyoto Shogoinkawara-cho, 54 606-8507, Japan
TEL	075-751-3153
Homepage URL
Email	jkanda16@kuhp.kyoto-u.ac.jp

Sponsor
Institute	HLA Working Group, the Japan Society for Hematopietic Cell Tranplantation. Research Grant for Allergic Disease and Immunology (H23-009) from the Japanese Ministry of Health, Labor, and Welfare.
Institute
Department

Funding Source
Organization	The Clinical research committee of the Japan Society for Hematopoietic Cell Transplantation
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Division of Hematology, Saitama Medical Center, Jichi Medical University
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Jichi Medical University Clinical Research Ethics Committee
Address	1-847 Amanuma-cho, Omiya-ku, Saitama City, Saitama 330-8503, Japan
Tel	048-647-2111
Email	yanaiakr@jichi.ac.jp

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	2013 Year 07 Month 16 Day

Related information
URL releasing protocol	https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000012652&ty
Publication of results	Published

Result
URL related to results and publications	https://journals.sagepub.com/doi/10.1177/0963689720976567?url_ver=Z39.88-2003&rfr_id=ori:rid:crossre
Number of participants that the trial has enrolled	39
Results	39 patients were eligible for the analysis. The 1-year GRFS was 47%. The 3-year OS was 57%. Age of less than 50 years was associated with better OS. OS in patients with high/very high refined disease risk indexes (rDRIs) was comparable to that in those with low/intermediate rDRIs. The 100-day cumulative incidences of grades II-IV and III-IV acute GVHD were 45% and 18%, respectively. Three-year cumulative incidences of moderate to severe or severe chronic GVHD were 13% and 3%, respectively.
Results date posted	2020 Year 12 Month 31 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	The median age of the patients included in the study was 51 years (range 16-64 years). Diagnoses were AML in 14 patients, ALL in 6, MDS in 4, CML in one, NHL in 8, ATL in 4, and HL in one. Eighteen patients received a transplant in CR1 or CP1, 3 in CR2 or more, and 13 in non-CR.
Participant flow	Thirty-nine patients were registered. One patient was ineligible because their serum aspartate aminotransferase level was >5 times the upper normal limit after registration.
Adverse events	Severe adverse events that should be reported occurred in 9 patients. (Death within 100 days: 3, Grade 4 acute GVHD: 2, Unexpected Grade 4; 1, Others 3)
Outcome measures	The primary endpoint was 1-year GRFS (GVHD-free relapse-free survival). Other assessed endpoints were overall survival, progression-free survival, relapse, non-relapse mortality, neutrophil and platelet engraftment, and acute and chronic GVHD.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 05 Month 09 Day
Date of IRB	2013 Year 07 Month 11 Day
Anticipated trial start date	2013 Year 08 Month 01 Day
Last follow-up date	2018 Year 06 Month 02 Day
Date of closure to data entry	2018 Year 12 Month 31 Day
Date trial data considered complete	2019 Year 03 Month 20 Day
Date analysis concluded	2020 Year 04 Month 21 Day

Other
Other related information

Management information
Registered date	2013 Year 07 Month 16 Day
Last modified on	2020 Year 12 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000012652