Back to resultsASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
Primary Purpose
Down Syndrome, Acute Lymphoblastic Leukemia, Childhood Cancer
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Daunorubicin
Prednisolone
Vincristine
Epirubicin
E-coli L-asparaginase
6-Mercaptopurine
Methotrexate
Hydrocortisone
Cytarabine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Down Syndrome
Eligibility Criteria
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:
- 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.
- Ongoing uncontrolled hypertension.
- Ongoing uncontrolled diabetes mellitus.
- Ongoing uncontrolled infection.
- History of congenital or acquired immunodeficiency including HIV infection.
- History of interstitial pneumonia, pulmonary fibrosis, bronchiectasis or severe pulmonary emphysema.
- CNS hemorrhage.
- Psychiatric disorder.
- 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.
Sites / Locations
- Prince of Wales HospitalRecruiting
- Kagoshima University HospitalRecruiting
- University of Malaya Medical Centre
- Subang Jaya Medical Centre
- National University HospitalRecruiting
- KK Women's and Children's HospitalRecruiting
- National Taiwan University Children's Hospital
- Mackay Memorial HospitalRecruiting
- Chang Gung Memorial Hopsital, Linkou
- Siriraj Hospital Mahidol UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
SR
LR
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Event Free Survival
Percentage of patients who are event free at 5 years.
Secondary Outcome Measures
Overall survival
Percentage of patients who survive at 5 years.
Disease free survival
Percentage of patients who are leukemia free at 5 years.
Induction failure
Percentage of patients who had failed induction.
Complete remission rate
Percentage of patients who had achieved complete remission at the end of induction.
Cumulative incidence of relapse
Incidence of treatment-related adverse events
Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms.
Flow MRD at day 15
To assess the prognostic value flow MRD level during induction for DS-ALL.
Full Information
NCT ID
NCT03286634
First Posted
August 9, 2017
Last Updated
September 26, 2022
Sponsor
National Hospital Organization Nagoya Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03286634
Brief Title
ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
Official Title
Asia-wide, Multicenter Open-label, Phase II Non-randomised Study Involving Children With Down Syndrome Under 21 Year-old With Newly Diagnosed, Treatment naïve Acute Lymphoblastic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 18, 2017 (Actual)
Primary Completion Date
March 31, 2028 (Anticipated)
Study Completion Date
March 31, 2033 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Hospital Organization Nagoya Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Down Syndrome, Acute Lymphoblastic Leukemia, Childhood Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
risk stratification-directed chemotherapy
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SR
Arm Type
Experimental
Arm Description
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.
Arm Title
LR
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Daunorubicin
Other Intervention Name(s)
DNR
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Other Intervention Name(s)
Pred
Intervention Description
Given PO or IV
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
VCR
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Other Intervention Name(s)
EPI
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
E-coli L-asparaginase
Other Intervention Name(s)
E-coli L-Asp
Intervention Description
Given IM or IV
Intervention Type
Drug
Intervention Name(s)
6-Mercaptopurine
Other Intervention Name(s)
6-MP
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
MTX
Intervention Description
Given IV, PO or IT
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
Given IT
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Ara-C
Intervention Description
Given IV, IT or SC
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cy
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Event Free Survival
Description
Percentage of patients who are event free at 5 years.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Percentage of patients who survive at 5 years.
Time Frame
Up to 5 years
Title
Disease free survival
Description
Percentage of patients who are leukemia free at 5 years.
Time Frame
Up to 5 years
Title
Induction failure
Description
Percentage of patients who had failed induction.
Time Frame
5 weeks
Title
Complete remission rate
Description
Percentage of patients who had achieved complete remission at the end of induction.
Time Frame
5 weeks
Title
Cumulative incidence of relapse
Time Frame
Up to 5 years
Title
Incidence of treatment-related adverse events
Description
Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms.
Time Frame
Up to 10 years
Title
Flow MRD at day 15
Description
To assess the prognostic value flow MRD level during induction for DS-ALL.
Time Frame
At day 15 of induction therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
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.
Ongoing uncontrolled hypertension.
Ongoing uncontrolled diabetes mellitus.
Ongoing uncontrolled infection.
History of congenital or acquired immunodeficiency including HIV infection.
History of interstitial pneumonia, pulmonary fibrosis, bronchiectasis or severe pulmonary emphysema.
CNS hemorrhage.
Psychiatric disorder.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Allen Yeoh, MBBS
Phone
(65) 67724406
Email
paeyej@nus.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allen Yeoh, MBBS
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Prince of Wales Hospital
City
Shatin
State/Province
New Territories
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chi Kong Li, MBBS
Email
ckli@cuhk.edu.hk
Facility Name
Kagoshima University Hospital
City
Kagoshima
ZIP/Postal Code
890-8544
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yasuhiro Okamoto
Email
okamoto@m2.kufm.kagoshima-u.ac.jp
Facility Name
University of Malaya Medical Centre
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hany Arrifin, MBBS
Email
hany@ummc.edu.my
Facility Name
Subang Jaya Medical Centre
City
Subang Jaya
ZIP/Postal Code
47500
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hai Peng Lin, MBBS
Email
flslhp@gmail.com
First Name & Middle Initial & Last Name & Degree
Lee Lee Chan, MBBS
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allen Yeoh, MBBS
Email
allen_yeoh@nuhs.edu.sg
Facility Name
KK Women's and Children's Hospital
City
Singapore
ZIP/Postal Code
229899
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ah Moy Tan, MBBS
Email
tan.ah.moy01@singhealth.com.sg
Facility Name
National Taiwan University Children's Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tsamn Lin Dong, MD
Email
dtlin@ntuh.gov.tw
Facility Name
Mackay Memorial Hospital
City
Taipei
ZIP/Postal Code
10449
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hsi-Che Liu, MD
Email
hsiche@mmh.org.tw
Facility Name
Chang Gung Memorial Hopsital, Linkou
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shih-Hsiang Chen, MD
Email
samechen@cgmh.org.tw
Facility Name
Siriraj Hospital Mahidol University
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jassada Buaboonnam, MD
Email
onco008@yahoo.com
12. IPD Sharing Statement
Learn more about this trial
ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
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