UMIN-CTR Clinical Trial

Public title

Randomized phase II trial to evaluate the effectiveness of azacitidine for low risk MDS.

Acronym

Randomized phase II trial to evaluate the effectiveness of azacitidine for low risk MDS.

Scientific Title

Randomized phase II trial to evaluate the effectiveness of azacitidine for low risk MDS.

Scientific Title:Acronym

Randomized phase II trial to evaluate the effectiveness of azacitidine for low risk MDS.

Region

Japan

Condition

lower risk myelodysplastic syndrome

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

The aim of this study is to evaluate the effectiveness to achieve hematological improvement with azacitidine for lower risk MDS with insufficient hematopoiesis, and to examine the maintenance efficacy of azacitidine maintenance therapy for responsive cases.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

This study has two primary endpoints for induction phase and maintenance phase, respectively.
Induction phase: the ratio of cases in which hematological improvement is achieved with 6 course of azacitidine therapy.
Maintenance phase: the ratio of patients who maintained hematological effectiveness achieved in the induction phase after one year with or without azacitidine maintenance therapy.

Key secondary outcomes

Induction phase:
Achievement ratio of hematological improvement for each of hematological series.
Cytogenetic response ratio.
Transfusion dependence ratio at the end of induction phase.
Sustainability of induction therapy.
Incidence of Grade 3 side effects or higher.
Incidence of infection that need intravenous antibiotics.
Overall survival ratio.
Progression free survival ratio to AML.

Maintenance phase:
the ratio of patients who maintained hematological effectiveness after two years.
Ratio of AML development.
Ratio of patients who received hematopoietic stem cell transplantation.
Incidence of Grade 3 side effects or higher.
Incidence of infection that need intravenous antibiotics.
Overall survival ratio.
Progression free survival ratio to AML.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

In the induction phase, there is no allocation. All the patients receive azacitidine 75mg/m2 for five consecutive days, and 21 days off. Repeat this treatment for six cycles.
In the maintenance phase, those who achieved hematological improvement are allocated randomly into therapy arm and observation arm. In the observation arm, patients halt azacitidine therapy and are followed up periodically (at least once over 3 months for one year after allocation).

Interventions/Control_2

In the therapy arm, patients receive azacitidine 75mg/m2 for 5 consecutive days per 28 days, and repeat this cycle until disease progression.

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

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Cases that are diagnosed as MDS according to WHO 2008 criteria. Include therapy related MDS, but does not include MDS/MPN.
2) Cases in low/Int-1 according to IPSS criteria at both diagnostic and enrollment time.
3) Cases with at least one lineage cytopenia. Concretely, at least one of the following criteria are met.
a) Hb<10g/dL and required RBC transfusions in the past 3 months.
b) Plt<50000/mm3 or with bleeding tendency.
c) Neu<1000/mm3 or with increased susceptibility to infection that require antibiotics.
4) Cases with expected life expectancy>1 year.
5) Aged 20 or older.
6) ECOG Performance Status 0~2
7) Cases with total bilirubin and serum creatinine level below 1.5xULN.
8) Cases with AST(GOT) or ALT(GPT) level below 3.0xULN.
9) Cases who can visit hospitals at the pre-defined schedule.
10) Cases with written informed consent.

Key exclusion criteria

1) Cases with scheduled hematopoietic stem cell transplantation. We do not exclude patients who are judged as transplant candidate after entry of this study because of change of medical conditions.
2) Cases who received hematopoietic stem cell transplantation.
3) Cases who had already been enrolled into other clinical trials for MDS.
4) Cases with pregnancy, possibility of pregnancy, in breast-feeding, or with plant to bear a child
5) Cases with hypersensitivity to azacitidine.
6) Cases with other cancers than MDS that is invasive within 5 years.
7) Cases with complicating diseases that are severe or uncontrolled.
8) Cases with psychiatric diseases or psychiatric symptoms that preclude adequate entry to the study.
9) Cases with cognitive disorders.
10) Patients who are receiving successful treatment with other modalities, or who are expected to achieve better response with other treatments (such as with 5q- syndrome).
11) Cases that are considered to be inadequate to enroll this study by the attending physicians.

Target sample size

100

Name of lead principal investigator

1st name
Middle name
Last name	Yasuhito Nannya

Organization

The University of Tokyo Hospital

Division name

Department of Hematology & Oncology

Zip code

Address

Hongo, 7-3-1, Bunkyo-ku, Tokyo

TEL

+81-3-3815-5411

Email

ynanya-tky@umin.ac.jp

Name of contact person

1st name
Middle name
Last name	Yasuhito Nannya

Organization

The University of Tokyo Hospital

Division name

Department of Hematology & Oncology

Zip code

Address

Hongo, 7-3-1, Bunkyo-ku, Tokyo

TEL

+81-3-3815-5411

Homepage URL

Email

ynanya-tky@umin.ac.jp

Institute

National Research Group on Idiopathic Bone Marrow Failure Syndromes

Institute

Department

Personal name

Organization

Grants from the Ministry of Health, Labor and Welfare of Japan
National Research Group on Idiopathic Bone Marrow Failure Syndromes

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

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

2013

Year

07

Month

01

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

Terminated

Date of protocol fixation

2013

Year

06

Month

10

Day

Date of IRB

Anticipated trial start date

2013

Year

07

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

06

Month

02

Day

Last modified on

2015

Year

06

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012707