UMIN-CTR Clinical Trial

Public title

A phase II study of antithymocyte globulin in patients undergoing HLA-matched allogeneic peripheral blood stem cell transplantation

Acronym

JSCT-ATG15

Scientific Title

A phase II study of antithymocyte globulin in patients undergoing HLA-matched allogeneic peripheral blood stem cell transplantation

Scientific Title:Acronym

JSCT-ATG15

Region

Japan

Condition

AML,ALL,HL,NHL

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate safety and efficacy of antithymocyte globulin (Thymoglobulin 1mg/kg, day -2, -1) in patients undergoing HLA-matched allogeneic peripheral blood stem cell transplantation after myeloablative conditioning

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The incidence of grade III-IV acute GVHD at 100 days

Key secondary outcomes

1. Engraftment at 100 days.
2. The incidence of acute GVHD and chronic GVHD at 100 days, 1 year, and 2 years.
3. Non-relapse mortality at 100 days, 1 year, and 2 years.
4. The incidence of relapse at 100 days, 1 year, and 2 years.
5. Disease-free survival at 100 days, 1 year, and 2 years.
6. Overall survival at 100 days, 1 year, and 2 years.
7. The incidence of infectious event at 100 days, 1 year, and 2 years.
8. GVHD free, relapse free survival (GRFS) at 100 days, 1 year, and 2 years.
9. The proportion of patients who stopped immunosuppressive drugs within 1 year and 2 year.
10. Grade 3-4 non-hematologic toxicity within 100 days.
11. Subgroup analysis subgroup analysis according to conditioning regimen.
12. Subgroup analysis subgroup analysis according to disease risk index (DRI)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1. Conditioning regimen
The definition of myeloablative conditioning regimen includes iv Busulfan > 7.2 mg/kg or Melphalan > 140 mg/m2 or TBI > 8 Gy.
:Cyclophosphamide (120 mg/kg) + TBI (12Gy/6fr)
:iv Busulfan (12.8 mg/kg) + Cyclophosphamide (120 mg/kg)
:Fludarabine (120-180 mg/m2) + iv Busulfan (12.8 mg/kg)
2. GVHD prophylaxis
Cyclosporine or Tacrolimus + MTX (day1: 10mg/m2, day 3, 6 (11): 7mg/m2)

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

Age-lower limit

15

years-old

<=

Age-upper limit

60

years-old

>=

Gender

Male and Female

Key inclusion criteria

1.Patients who have hematologic malignancies as defined at least one of the following:
a) Acute Leukemia, CR
b) Myelodysplastic syndrome
intermediate-II, high as defined by IPSS
high, very high as defined by WPSS
c) Lymphoma, CR or chemosensitive PR
2.Age: 15-60 years old.
3.Patients who have HLA 8/8 matched related or unrelated peripheral blood stem cell donor
4.Performance status: 0-2
5.Patients with adequate physical function (Cardiac, Hepatic, Renal, Pulmonary).
6.Patients who give written informed consent to participate in the study.

Key exclusion criteria

1. Patients who are positive for HIV antibody.
2. Patients with active other malignancies.
3. Patients with active infectious disease.
4. Women who are pregnant, of childbearing potential, or lactating.
5. Patients who experienced serious hypersensitivity or anaphylaxis to antithymocyte globulin.
6. Patients who has a prior history of allogeneic transplantation.
7. Patients who are not eligible for this study at the discretion of the investigator.

Target sample size

70

Name of lead principal investigator

1st name	Junichi
Middle name
Last name	Sugita

Organization

Hokkaido University Hospital

Division name

Department of Hematology

Zip code

060-8638

Address

060-8638 Sappor

TEL

011-

Email

jsct-office@umin.ac.jp

Name of contact person

1st name	Junichi
Middle name
Last name	Sugita

Organization

JSCT

Division name

ATG15-DC

Zip code

104-0031

Address

104-0031

TEL

03-6225-2025

Homepage URL

Email

jsct-office@umin.ac.jp

Institute

JSCT

Institute

Department

Personal name

Organization

Resarch Foundation for Community Medicine

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Hokkaido University Hospital

Address

060-8638

Tel

011

Email

jsct-office@umin.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2015

Year

10

Month

01

Day

URL releasing protocol

https://doi.org/10.1038/s41409-020-0985-3

Publication of results

Unpublished

URL related to results and publications

https://doi.org/10.1038/s41409-020-0985-3

Number of participants that the trial has enrolled

77

Results

Low-dose ATG as a GVHD prophylaxis showed safety and efficacy for the prevention of both
acute and chronic GVHD in HLA-matched PBSCT
using myeloablative conditioning.

Results date posted

2022

Year

09

Month

18

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Sex (Male / Female):40 / 32
Age (median years (range)):46.5 (19 - 60)
Disease:AML 37/ALL 19/MDS 8/ML 5/Other
leukemias 3
Disease status:CR 62/Others 10
Performance status:PS0 61/PS1 11
Stem cell source:Related 50/Unrelated 22

Participant flow

The first patient was registered in January 2016, and on July 24, 2018, the target number of cases of 70 cases was reached, but there were 5 ineligible cases. The patient registration was continued on the 31st. A total of 77 registered cases were registered from 23 institutions.

Adverse events

The incidence of major grade 3 or higher adverse events up to 30 days after transplantation was stomatitis 25%, nausea and vomiting 24%, diarrhea 9%, infection 13%, and Febrile neutropenia (FN) 18%. Up to 1 year after transplantation, the incidence of cytomegalovirus infection was 5.6%, the incidence of EB virus infection was absent, and the incidence of infection-related death was 4.2%.

Outcome measures

Grade III-IV acute GVHD incidence up to day 100, the primary endpoint, was 1.4% (95%CI; 0.1%-6.7%), which was significantly below the threshold (18%) used to calculate the number of cases.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2015

Year

08

Month

12

Day

Date of IRB

2015

Year

11

Month

13

Day

Anticipated trial start date

2015

Year

11

Month

01

Day

Last follow-up date

2020

Year

12

Month

24

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

08

Month

11

Day

Last modified on

2022

Year

09

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021586