UMIN-CTR Clinical Trial

Public title

A pilot phase I study of azacitidine for the first relapsed patients with infant acute lymphoblastic leukemia and MLL gene rearrangement

Acronym

AZA-MLL-P16

Scientific Title

A pilot phase I study of azacitidine for the first relapsed patients with infant acute lymphoblastic leukemia and MLL gene rearrangement

Scientific Title:Acronym

AZA-MLL-P16

Region

Japan

Condition

Children with first relapsed infant MLL gene rearrangement positive acute lymphoblastic leukemia

Classification by specialty

Hematology and clinical oncology

Pediatrics

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The primary aim of the study is to evaluate a safety of azacitidine (AZA) for children with relapsed infant MLL gene rearrangement positive acute lymphoblastic leukemia. An efficacy of AZA will be evaluated as a secondary aim.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase I

Primary outcomes

Occurrence rate of dose limiting toxicity (DLT)

Key secondary outcomes

1. Complete remission (CR) rate at the end of the test drug (AZA) administration.
2. CR rate at the end of the trial.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

NO

Dynamic allocation

NO

Institution consideration

Blocking

NO

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Either DL1 or DL0 would be given as a trial therapy.
DL1: AZA 2.5mg/kg/dose, 30min DIV, 7 days
DL0: AZA 2mg/kg/dose, 30min DIV, 7 days

Following 7-day of AZA, one course of chemotherapy selected by the physician will be given.

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

6

years-old

>=

Gender

Male and Female

Key inclusion criteria

Patients should meet all the criteria listed below:
(1) Patients must be diagnosed as B-cell precursor acute lymphoblastic leukemia (ALL) with MLL gene rearrangement confirmed by FISH.
(2) Patients must be a first relapsed case.
(3) Patients must be less than 1 year old at the time of initial ALL diagnosis.
(4) Patients must be in complete remission following one course of standard induction chemotherapy for relapsed ALL.
(5) All patients' parents or legal guardians must sign a written informed consent.
(6) Patients must have performance score (PS) of 0 to 3.
(7) Patients' peripheral blood cell counts must meet the following criteria;
1. ANC 500/mcL or higher, after 48 hours or longer cessation of G-CSF.
2. Platelet count 50,000/mcL or higher, without platelet transfusion within 3 days.
(8) Patients must have sufficient organ function (liver, kidney, heart, lung) at the trial entry;
1. SpO2 96% or higher in room air, no abnormal findings in chest X-ray.
2. No abnormal ECG and UCG findings which require interventions.
3. AST and ALT value within 5 times of normal upper limit.
4. Serum bilirubin value within 2 times of normal upper limit.
5. Creatinine value within 2 times of normal upper limit.

Key exclusion criteria

Patients should be excluded if either of the below criteria is met:
(1) Patients with uncontrollable infections.
(2) Patients with congenital heart disease which require any interventions.
(3) Patients with somatic chromosomal abnormalities.
(4) Patients with active hemorrhage at study entry.
(5) Patients with CNS symptoms at study entry.
(6) Patients with other malignant diseases.
(7) Patients with isolated extramedullary relapse.
(8) Patients with CNS relapse.
(9) Patients not eligible for the study entry decided by the primary/co-investigators of the study.

Target sample size

12

Name of lead principal investigator

1st name	Daisuke
Middle name
Last name	Tomizawa

Organization

National Center for Child Health and Development

Division name

Children's Cancer Center

Zip code

157-8535

Address

2-10-1 Okura, Setagaya-ku, Tokyo, Japan

TEL

03-3416-0181

Email

tomizawa-d@ncchd.go.jp

Name of contact person

1st name	Daisuke
Middle name
Last name	Tomizawa

Organization

National Center for Child Health and Development

Division name

Children's Cancer Center

Zip code

157-8535

Address

2-10-1 Okura, Setagaya-ku, Tokyo, Japan

TEL

03-3416-0181

Homepage URL

Email

tomizawa-d@ncchd.go.jp

Institute

National Center for Child Health and Development

Institute

Department

Personal name

Organization

A grant from National Center for Child Health and Development #27-4 "Studies on developing novel therapy for rare subtype of refractory leukemia.lymphoma in children"

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Institutioanl Review Board of National Center for Child Health and Development

Address

2-10-1 Okura, Setagaya-ku, Tokyo

Tel

03-3416-0181

Email

hagino-k@ncchd.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立研究開発法人　国立成育医療研究センター（東京都）

Date of disclosure of the study information

2017

Year

10

Month

01

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs031180063

Publication of results

Unpublished

URL related to results and publications

https://jrct.niph.go.jp/latest-detail/jRCTs031180063

Number of participants that the trial has enrolled

1

Results

Primary endpoint of this trial was incidence of dose limiting toxicity (DLT) of the investigational drug azacytidine. No DLT was observed in DL1 for the registered patient. However, at least three patients are required to evaluate the incidence of DLT in DL1; therefore, DLT of azacitidine could not be evaluated in this study.

Results date posted

2023

Year

03

Month

05

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Total three patients were screened for registration of the trial, and one patient registered and was eligible.
This patient was assigned to the dose level 1 (DL1). Baseline characteristics of the patient was as follows.

Age at diagnosis: 0 year old at initial diagnosis,
one year old at relapse
Sex: Female
Diagnosis: MLL gene-rearranged B-cell
precursor acute lymphoblastic leukemia (B-ALL),
first bone marrow relapse

Participant flow

This trial is a Phase I clinical trial, and was initiated on September 11, 2017. One patient registered to the trial (assigned to DL1), and completed the trial therapy. Trial registration ended on March 31, 2022. Because the follow up period (6 months after patient registration) of the registered patient was already completed, follow-up period of the total study ended on March 31, 2022 as well.

Along with the enactment and enforcement of the Clinical Trials Act in Japan, this trial obtained approval as a specified clinical trial from the certified review board on November 19, 2018, and was released in jRCT on December 27, 2018.

Adverse events

No severe adverse events were reported.

Outcome measures

Primary endpoint of this trial was incidence of dose limiting toxicity (DLT) of the investigational drug azacytidine.
Secondary endpoints included maintenance rate of complete remission (CR) at the end of azacitidine completion and at the end of the trial period.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

09

Month

11

Day

Date of IRB

2017

Year

08

Month

31

Day

Anticipated trial start date

2017

Year

10

Month

01

Day

Last follow-up date

2022

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

09

Month

25

Day

Last modified on

2023

Year

03

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033461