UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000011192 |
|---|---|
| Receipt number | R000012652 |
| 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. |
| Date of disclosure of the study information | 2013/07/16 |
| Last modified on | 2020/12/31 11:06:45 |
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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
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
jkanda16@kuhp.kyoto-u.ac.jp
Sponsor or person
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
Personal name
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
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
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012652
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