UMIN-CTR Clinical Trial

Public title

Exploratory study using comprehensive coagulation and fibrinolysis functional analysis for hemostatic disorders associated with initial induction therapy and early consolidation therapy in pediatric, AYA and adult-onset B-precursor or T-cell acute lymphoblastic leukemia - A multi-factor analysis study incorporating trends in L-asparaginase activity

Acronym

JPLSG-ThrombALL-B19&T19

Scientific Title

Exploratory study using comprehensive coagulation and fibrinolysis functional analysis for hemostatic disorders associated with initial induction therapy and early consolidation therapy in pediatric, AYA and adult-onset B-precursor or T-cell acute lymphoblastic leukemia - A multi-factor analysis study incorporating trends in L-asparaginase activity

Scientific Title:Acronym

JPLSG-ThrombALL-B19&T19

Region

Japan

Condition

B-precursor or T-cell acute lymphoblastic leukemia

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

The objective is to analyze the tendency of comprehensive coagulation/fibrinolysis balance using thrombin-plasmin generation assay during from the L-asparaginase treatment phase of induction therapy to the end of early consolidation therapy in the BFM backbone protocol in newly diagnosed cases of B-precursor and T-cell acute lymphoblastic leukemia in pediatric, AYA, and adults, in order to understand the pathogenesis of L-asparaginase-related hemostatic disorders. It is hoped that this study will provide essential data that will lead to the establishment of safe and effective treatments and appropriate supportive care.

Basic objectives2

Others

Basic objectives -Others

In cases where thrombosis occurs during treatment or significant coagulation/fibrinolysis disorders are observed and the presence or absence of a thrombophilia predisposition is unknown, the presence or absence of pathological variants in the genome will be examined to determine if genetic background influences the frequency of thrombosis (/ bleeding symptoms).

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Alterations in the comprehensive coagulation/fibrinolysis balance from the L-Asp treatment phase of initial induction therapy to the end of early consolidation therapy: Trends in thrombin-plasmin generation assay parameters.

Key secondary outcomes

From the L-Asp treatment phase of initial induction therapy to the end of early consolidation therapy:
1) Changes in platelet counts and conventional coagulation fibrinolysis markers.
2) Frequency of anticoagulation and transfusion therapy.
3) Frequency of hemostatic disorders (bleeding symptoms, thrombosis).
4) Comparison of the frequency of coagulopathy (bleeding symptoms, thrombosis) by age group (<10 years vs. &ge;10 years vs. &ge;15 years).
5) Comparison of the frequency of hemostatic disorders (bleeding symptoms, thrombosis) in patients with and without thrombophilia.
6) Comparison of the frequency of hemostatic disorders by the presence or absence of infections affecting bleeding symptoms or thrombosis.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

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

Not applicable

Age-upper limit

40

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Patients enrolled at Japan Children's Cancer Group (JCCG) sites in the JPLSG-ALL-B19 or T19 Study conducted jointly by the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) and the Japan Adult Leukemia Study Group (JALSG).
2) Investigators 16 years of age or older who have obtained written consent to participate in the JPLSG-ThrombALL-B19&T19 study from the patient himself/herself (or from a legal guardian if the patient is a minority).

Key exclusion criteria

1) Infant ALL cases treated with a protocol other than the BFM backbone.
2) Ineligible cases such as Philadelphia chromosome-positive cases among ALL patients aged 1 year or older.
3) Other cases that the investigator or physician in charge of the study determines are not appropriate for participation in the study.

Target sample size

350

Name of lead principal investigator

1st name	Takashi
Middle name
Last name	Ishihara

Organization

Nara Medical University

Division name

Department of Pediatrics

Zip code

634-8522

Address

840 Shijo-cho, Kashihara, Nara

TEL

0744-22-3051

Email

takakun@naramed-u.ac.jp

Name of contact person

1st name	Takashi
Middle name
Last name	Ishihara

Organization

Nara Medical University

Division name

Department of Pediatrics

Zip code

634-8522

Address

840 Shijo-cho, Kashihara, Nara

TEL

0744-22-3051

Homepage URL

Email

takakun@naramed-u.ac.jp

Institute

Nara Medical University

Institute

Department

Personal name

Takashi Ishihara

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Grants-in-Aid for Scientific Research

Organization

Nara Medical University Ethics Committee

Address

840 Shijo-cho, Kashihara, Nara

Tel

0744-22-3051

Email

ino_rinri@naramed-u.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

2024

Year

06

Month

17

Day

URL releasing protocol

Publication of results

Unpublished

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

Recruitment status

Open public recruiting

Date of protocol fixation

2021

Year

12

Month

27

Day

Date of IRB

2021

Year

12

Month

27

Day

Anticipated trial start date

2022

Year

01

Month

21

Day

Last follow-up date

2028

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Exploratory Endpoints
1) Changes in total PAI-1 antigen from the L-Asp treatment phase of initial induction therapy to the end of early consolidation therapy.
2) Identification of pathological variants of genes associated with hemostatic disorders (bleeding symptoms, thrombosis).
3) Frequency of decreased L-Asp activity, silent inactivation, and anti-L-Asp antibody production.
4) Association between the presence of anti-L-Asp antibodies and allergic reactions and anaphylaxis.
5) Comparison of L-Asp activity levels and anti-L-Asp antibody titers between the onset of allergy with Leunase and the last dose of Erwinase.
6) Comparison of the frequency of occurrence of decreased L-Asp activity and the frequency of allergic reactions and anaphylaxis by age group (<10 years vs. &ge;10 years and <15 years vs. &ge;15 years).
7) Examination of differences in the patterns of variation of comprehensive thrombin-plasmin generation assay and conventional coagulation/fibrinolysis markers between cases with and without decreased L-Asp activity.
8) Evaluation of differences of the pattern of variation between the thrombin-plasmin generation assay and conventional coagulation fibrinolysis markers in the conventional Leunase from E. coli and PEG-Asp formulation (Oncaspar).

Registered date

2024

Year

06

Month

16

Day

Last modified on

2024

Year

06

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000062475