ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

NCT ID: NCT03286634

Last Updated: 2022-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-18

Study Completion Date

2033-03-31

Brief Summary

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To evaluate the outcome of a prednisolone and low dose methotrexate based protocol in Down syndrome children with ALL (DS-ALL) in an Asia-wide study. The treatment protocol was modified based upon backbone of Taiwan Pediatric Oncology Group (TPOG)-ALL protocol in which risk classification will be guided by level of flow minimal residual disease (MRD) instead.

Detailed Description

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Conditions

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Down Syndrome Acute Lymphoblastic Leukemia Childhood Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

risk stratification-directed chemotherapy
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SR

Standard Risk (SR) :

CNS 3 or CNS 2 regardless of response OR Time-point #1 (Day 15 induction) Flow MRD ≥ 1% (treatment will not be de-escalated even MRD \<0.01% by TP#2) OR Time-point #2 (Day 1 IDMTX/MP of Consolidation) ≥0.01%

SR strategy:

All SR patient will have to receive two doses of anthracycline and 12 L-asparaginase doses during induction except those who are escalated to SR at time point 2 when MRD ≥0.01%.

During the first year of maintenance phase (48 weeks; 4x12 weeks blocks), cyclophosphamide and cytarabine bolus will be administered at 4 weekly interval.

Group Type EXPERIMENTAL

Daunorubicin

Intervention Type DRUG

Given IV

Prednisolone

Intervention Type DRUG

Given PO or IV

Vincristine

Intervention Type DRUG

Given IV

Epirubicin

Intervention Type DRUG

Given IV

E-coli L-asparaginase

Intervention Type DRUG

Given IM or IV

6-Mercaptopurine

Intervention Type DRUG

Given PO

Methotrexate

Intervention Type DRUG

Given IV, PO or IT

Hydrocortisone

Intervention Type DRUG

Given IT

Cytarabine

Intervention Type DRUG

Given IV, IT or SC

Cyclophosphamide

Intervention Type DRUG

Given IV

LR

Low Risk (LR):

Time-point #1 (Day 15 induction) Flow MRD \<1% AND Time-point #2 (Day 1 IDMTX/MP of Consolidation) \<0.01% AND CNS 1 only

LR strategy:

For LR patients, one dose of anthracycline and 3 doses of L-asparaginase will be omitted during induction.

Following re-induction I, interim maintenance and additional block of re-induction ie. re-induction II prior to maintenance phase will be omitted for LR patients.

Group Type EXPERIMENTAL

Daunorubicin

Intervention Type DRUG

Given IV

Prednisolone

Intervention Type DRUG

Given PO or IV

Vincristine

Intervention Type DRUG

Given IV

Epirubicin

Intervention Type DRUG

Given IV

E-coli L-asparaginase

Intervention Type DRUG

Given IM or IV

6-Mercaptopurine

Intervention Type DRUG

Given PO

Methotrexate

Intervention Type DRUG

Given IV, PO or IT

Hydrocortisone

Intervention Type DRUG

Given IT

Interventions

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Daunorubicin

Given IV

Intervention Type DRUG

Prednisolone

Given PO or IV

Intervention Type DRUG

Vincristine

Given IV

Intervention Type DRUG

Epirubicin

Given IV

Intervention Type DRUG

E-coli L-asparaginase

Given IM or IV

Intervention Type DRUG

6-Mercaptopurine

Given PO

Intervention Type DRUG

Methotrexate

Given IV, PO or IT

Intervention Type DRUG

Hydrocortisone

Given IT

Intervention Type DRUG

Cytarabine

Given IV, IT or SC

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Other Intervention Names

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DNR Pred VCR EPI E-coli L-Asp 6-MP MTX Ara-C Cy

Eligibility Criteria

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Inclusion Criteria

* Down syndrome diagnosed clinically or cytogenetically (including Mosaic Down)
* Newly diagnosed ALL according to WHO 2016 classification.
* Age \< 21 years old at time of enrollment.
* ECOG performance status (PS) score of 0-2.
* Written informed consent obtained from legally acceptable representatives.

Exclusion Criteria

* Second malignancy.
* Philadelphia positive ALL.
* Mature B-ALL.
* Mixed phenotype acute leukemia.
* Any previous treatment with cytotoxic chemotherapy excluding treatment for TAM or radiation therapy. Patient pre-treated with short term steroid (\< 7 days of duration within last 1 month prior to treatment start) can be enrolled into this study.
* Renal dysfunction with creatinine \>2x upper limit of normal (ULN). Patients whose creatinine has improved to \<2x ULN before treatment commencement can enrol subject to discretion of site PI.
* Liver dysfunction with direct bilirubin \> 5x ULN.
* Any serious uncontrolled medical condition or impending end organ dysfunction that would impair the ability of the subject to receive protocol therapy, including:

1. History of coronary arterial disease, cardiomyopathy, heart failure, arrhythmia (other than sinus arrhythmia) or severe cardiac malformation which with residual abnormalities or requires further major corrective surgery within 2 years.
2. Ongoing uncontrolled hypertension.
3. Ongoing uncontrolled diabetes mellitus.
4. Ongoing uncontrolled infection.
5. History of congenital or acquired immunodeficiency including HIV infection.
6. History of interstitial pneumonia, pulmonary fibrosis, bronchiectasis or severe pulmonary emphysema.
7. CNS hemorrhage.
8. Psychiatric disorder.
9. Other concurrent active neoplasms.
* Pregnant or lactating women.
* Doubtful compliance or ability to complete study therapy due to financial, social, familial or geographic reason, or in the judgement of site investigator.
Minimum Eligible Age

0 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Hospital Organization Nagoya Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Allen Yeoh, MBBS

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

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Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Site Status RECRUITING

Kagoshima University Hospital

Kagoshima, , Japan

Site Status RECRUITING

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status NOT_YET_RECRUITING

Subang Jaya Medical Centre

Subang Jaya, , Malaysia

Site Status NOT_YET_RECRUITING

National University Hospital

Singapore, , Singapore

Site Status RECRUITING

KK Women's and Children's Hospital

Singapore, , Singapore

Site Status RECRUITING

National Taiwan University Children's Hospital

Taipei, , Taiwan

Site Status NOT_YET_RECRUITING

Mackay Memorial Hospital

Taipei, , Taiwan

Site Status RECRUITING

Chang Gung Memorial Hopsital, Linkou

Taoyuan District, , Taiwan

Site Status NOT_YET_RECRUITING

Siriraj Hospital Mahidol University

Bangkok, , Thailand

Site Status RECRUITING

Countries

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Hong Kong Japan Malaysia Singapore Taiwan Thailand

Central Contacts

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Allen Yeoh, MBBS

Role: CONTACT

(65) 67724406

Facility Contacts

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Chi Kong Li, MBBS

Role: primary

Yasuhiro Okamoto

Role: primary

Hany Arrifin, MBBS

Role: primary

Hai Peng Lin, MBBS

Role: primary

Allen Yeoh, MBBS

Role: primary

Ah Moy Tan, MBBS

Role: primary

Tsamn Lin Dong, MD

Role: primary

Hsi-Che Liu, MD

Role: primary

Shih-Hsiang Chen, MD

Role: primary

Jassada Buaboonnam, MD

Role: primary

Other Identifiers

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ASIA-DS-ALL-2016

Identifier Type: -

Identifier Source: org_study_id

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