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ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

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ClinicalTrials.gov Identifier: NCT03286634
Recruitment Status : Recruiting
First Posted : September 18, 2017
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
National Hospital Organization Nagoya Medical Center

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.

Condition or disease Intervention/treatment Phase
Down Syndrome Acute Lymphoblastic Leukemia Childhood Cancer Drug: Daunorubicin Drug: Prednisolone Drug: Vincristine Drug: Epirubicin Drug: E-coli L-asparaginase Drug: 6-Mercaptopurine Drug: Methotrexate Drug: Hydrocortisone Drug: Cytarabine Drug: Cyclophosphamide Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: risk stratification-directed chemotherapy
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 18, 2018
Estimated Primary Completion Date : March 31, 2028
Estimated Study Completion Date : March 31, 2033


Arm Intervention/treatment
Experimental: 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.

Drug: Daunorubicin
Given IV
Other Name: DNR

Drug: Prednisolone
Given PO or IV
Other Name: Pred

Drug: Vincristine
Given IV
Other Name: VCR

Drug: Epirubicin
Given IV
Other Name: EPI

Drug: E-coli L-asparaginase
Given IM or IV
Other Name: E-coli L-Asp

Drug: 6-Mercaptopurine
Given PO
Other Name: 6-MP

Drug: Methotrexate
Given IV, PO or IT
Other Name: MTX

Drug: Hydrocortisone
Given IT

Drug: Cytarabine
Given IV, IT or SC
Other Name: Ara-C

Drug: Cyclophosphamide
Given IV
Other Name: Cy

Experimental: 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.

Drug: Daunorubicin
Given IV
Other Name: DNR

Drug: Prednisolone
Given PO or IV
Other Name: Pred

Drug: Vincristine
Given IV
Other Name: VCR

Drug: Epirubicin
Given IV
Other Name: EPI

Drug: E-coli L-asparaginase
Given IM or IV
Other Name: E-coli L-Asp

Drug: 6-Mercaptopurine
Given PO
Other Name: 6-MP

Drug: Methotrexate
Given IV, PO or IT
Other Name: MTX

Drug: Hydrocortisone
Given IT




Primary Outcome Measures :
  1. Event Free Survival [ Time Frame: Up to 5 years ]
    Percentage of patients who are event free at 5 years.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 5 years ]
    Percentage of patients who survive at 5 years.

  2. Disease free survival [ Time Frame: Up to 5 years ]
    Percentage of patients who are leukemia free at 5 years.

  3. Induction failure [ Time Frame: 5 weeks ]
    Percentage of patients who had failed induction.

  4. Complete remission rate [ Time Frame: 5 weeks ]
    Percentage of patients who had achieved complete remission at the end of induction.

  5. Cumulative incidence of relapse [ Time Frame: Up to 5 years ]
  6. Incidence of treatment-related adverse events [ Time Frame: Up to 10 years ]
    Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms.

  7. Flow MRD at day 15 [ Time Frame: At day 15 of induction therapy ]
    To assess the prognostic value flow MRD level during induction for DS-ALL.



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Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03286634


Contacts
Contact: Allen Yeoh, MBBS (65) 67724406 allen_yeoh@nuhs.edu.sg

Locations
Hong Kong
Prince of Wales Hospital Recruiting
Shatin, New Territories, Hong Kong
Contact: Chi Kong Li, MBBS       ckli@cuhk.edu.hk   
Japan
Kagoshima University Hospital Recruiting
Kagoshima, Japan, 890-8544
Contact: Yasuhiro Okamoto       okamoto@m2.kufm.kagoshima-u.ac.jp   
Malaysia
University of Malaya Medical Centre Not yet recruiting
Kuala Lumpur, Malaysia, 59100
Contact: Hany Arrifin, MBBS       hany@ummc.edu.my   
Subang Jaya Medical Centre Not yet recruiting
Subang Jaya, Malaysia, 47500
Contact: Hai Peng Lin, MBBS       flslhp@gmail.com   
Sub-Investigator: Lee Lee Chan, MBBS         
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119074
Contact: Allen Yeoh, MBBS       allen_yeoh@nuhs.edu.sg   
KK Women's and Children's Hospital Not yet recruiting
Singapore, Singapore, 229899
Contact: Ah Moy Tan, MBBS       tan.ah.moy01@singhealth.com.sg   
Taiwan
National Taiwan University Children's Hospital Not yet recruiting
Taipei, Taiwan, 100
Contact: Tsamn Lin Dong, MD       dtlin@ntuh.gov.tw   
Mackay Memorial Hospital Not yet recruiting
Taipei, Taiwan, 10449
Contact: Hsi-Che Liu, MD       hsiche@mmh.org.tw   
Chang Gung Memorial Hopsital, Linkou Not yet recruiting
Taoyuan, Taiwan, 333
Contact: Shih-Hsiang Chen, MD       samechen@cgmh.org.tw   
Sponsors and Collaborators
National Hospital Organization Nagoya Medical Center
Investigators
Principal Investigator: Allen Yeoh, MBBS National University Hospital, Singapore

Responsible Party: National Hospital Organization Nagoya Medical Center
ClinicalTrials.gov Identifier: NCT03286634     History of Changes
Other Study ID Numbers: ASIA-DS-ALL-2016
First Posted: September 18, 2017    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Down Syndrome
Syndrome
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Cyclophosphamide
Methotrexate
Cytarabine
6-Mercaptopurine
Vincristine
Prednisolone
Epirubicin
Daunorubicin
Asparaginase