UMIN-CTR Clinical Trial

Basic information
Public title	HLA-haploidentical stem cell transplantation using a low dose ATG and steroid
Acronym	HLA-haploidentical RIST
Scientific Title	HLA-haploidentical stem cell transplantation using a low dose ATG and steroid
Scientific Title:Acronym	HLA-haploidentical RIST
Region	Japan

Condition
Condition	acute myeloid leukemia, acute lymphoid leukemia/first or second allogeneic stem cell transplantation
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	HLA-haploidentical stem cell transplantation using a low-dose anti-T-lymphocyte globulin (ATG) and steroid is expected to evert a strong graft-versus-leukemia effect. In the present study, whether this transplant procedure can improve the survival of patients with poor prognosis is analyzed.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	This is a prospective, multi-center (5 transplant centers) study of HLA-haplidentical stem cell transplantation. A hundred patients are planning to be enrolled. The major outcome is survival on day 100.
Key secondary outcomes	1. The incidence and severity of acute GVHD 2. The incidence and severity of chronic GVHD 3. Survival rate at 1 year 4. Disease-free survival rate at 1 year 5. transplant-related mortality at 1 year 6. The incidence of infection (bacterial, fungus, virus, others) 7. Immunological recovery 8. Iron overload 9. The concentration of ATG on days 0 and 7. 10. donor T cell repertoire analysis

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Maneuver
Interventions/Control_1	Patients with AML or ALL at poor risk undergo transplantation using peripheral blood stem cells from an HLA-haploidsentical donor. The conditioning treatment consists of fludarabine 30 mg/m2/day x 6 (days -9 to -4), melphalan 70 mg/m2/day x 2 (days -3 to -2), thymoglobulin 1.25 mg/kg/day x 2 (days -2 to -1), and total body irradiation 3 Gy on day 0. When patients have bone marrow blasts > 20%, cytarabine 2 g/m2/day x 4 (days -9 to -6) is added. Peripheral blood stem cells containing 3.0-10.0 CD34 cells/kg (patients' body weight) is infused on day 0. GVHD prophylaxis consists of tacrolimus and methylprednisolone 1 mg/kg. Tacrolimus and methylprednisolone are started on day -2 and 0, respectively.
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	60 years-old >=
Gender	Male and Female
Key inclusion criteria	1. A related donor who is matched or 1 antigen-mismatched in HLA-A, -B, and -DR antigen is not available. 2. An unrelated donor who is matched in HLA-A, -B, -DR antigen, and allelic mismatched 0 or 1 locus in HLA-A, -B, -DR loci is not available. When patients is an urgent situation, those are eligible. 3. A related HLA-haploidentical donor is available. 4. Disease status; for AML, any status other than first CR is eligible. Patients with AML in first CR with poor karyotype, MRD positivity, FLT-ITD mutation(+), M0, and induction failure after first induction therapy are eligible. For ALL, patients in any status is eligible. 5. Patients who undergo first or second allogeneic stem cell transplantation are eligible. 6. Performance status is 0 or 1 in ECOG criteria. 7. Patients do not have an organ failure, including heart, lung, liver, and kidney, as follows: 1) Ejection friction >50%, 2) SO2>93%, 3) T bilirubin <2.0 mg/dl and AST <2.5 times the normal upper limit, 4) serum creatinine level <1.5 times the normal upper limit.
Key exclusion criteria	1. A history of adverse events for agents used in the conditioning treatment or GVHD prophylaxis. 2. Active CNS disorders other than leukemia. 3. Active infection. 4. Doctor's decision that patients are inappropriate for this study in some reasons.
Target sample size	100

Research contact person
Name of lead principal investigator	1st name Middle name Last name Hiroyasu Ogawa
Organization	Hyogo College of Medicine
Division name	Division of Hematology, Department of Internal Medicine
Zip code
Address	1-1, Mukogawa-machi, Nishinomiya city, Hyogo
TEL	0798-45-6886
Email	ogawah@hyo-med.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Hiroyasu Ogawa
Organization	Hyogo College of Medicine
Division name	Division of Hematology, Department of Internal Medicine
Zip code
Address	1-1, Mukogawa-machi, Nishinomiya city, Hyogo
TEL	0798-45-6886
Homepage URL
Email	ogawah@hyo-med.ac.jp

Sponsor
Institute	Hyogo College of Medicine
Institute
Department

Funding Source
Organization	Ministry of Education, Culture, Sports, Science and Technology
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Saiseikai Maebashi Hospital, Japanese Red Cross Nagoya First Hospital, Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

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	がん･感染症センター都立駒込病院 (東京都)、群馬県済生会前橋病院 (群馬県)、名古屋第一赤十字病院 (愛知県)、東北大学病院 (宮城県)

Other administrative information
Date of disclosure of the study information	2017 Year 08 Month 27 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2017 Year 06 Month 12 Day
Date of IRB	2017 Year 06 Month 12 Day
Anticipated trial start date	2017 Year 08 Month 27 Day
Last follow-up date	2023 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 08 Month 26 Day
Last modified on	2020 Year 04 Month 05 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032948