Clinical Trials /

ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

NCT03286634

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: ASIA-DS-ALL-2016
  • NCT ID: NCT03286634

Conditions

  • Down Syndrome
  • Acute Lymphoblastic Leukemia
  • Childhood Cancer

Interventions

DrugSynonymsArms
DaunorubicinDNRSR
PrednisolonePredSR
VincristineVCRSR
EpirubicinEPISR
E-coli L-asparaginaseE-coli L-AspSR
6-Mercaptopurine6-MPSR
MethotrexateMTXSR
HydrocortisoneSR
CytarabineAra-CSR
CyclophosphamideCySR

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
SRExperimentalStandard 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.
  • Daunorubicin
  • Prednisolone
  • Vincristine
  • Epirubicin
  • E-coli L-asparaginase
  • 6-Mercaptopurine
  • Methotrexate
  • Hydrocortisone
  • Cytarabine
  • Cyclophosphamide
LRExperimentalLow 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.
  • Daunorubicin
  • Prednisolone
  • Vincristine
  • Epirubicin
  • E-coli L-asparaginase
  • 6-Mercaptopurine
  • Methotrexate
  • Hydrocortisone

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:

               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.
      
Maximum Eligible Age:20 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Percentage of patients who are event free at 5 years.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:Percentage of patients who survive at 5 years.
Measure:Disease free survival
Time Frame:Up to 5 years
Safety Issue:
Description:Percentage of patients who are leukemia free at 5 years.
Measure:Induction failure
Time Frame:5 weeks
Safety Issue:
Description:Percentage of patients who had failed induction.
Measure:Complete remission rate
Time Frame:5 weeks
Safety Issue:
Description:Percentage of patients who had achieved complete remission at the end of induction.
Measure:Cumulative incidence of relapse
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Incidence of treatment-related adverse events
Time Frame:Up to 10 years
Safety Issue:
Description:Incidence of treatment-related infectious and metabolic complications (throughout various phases of study therapy) and secondary neoplasms.
Measure:Flow MRD at day 15
Time Frame:At day 15 of induction therapy
Safety Issue:
Description:To assess the prognostic value flow MRD level during induction for DS-ALL.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Hospital Organization Nagoya Medical Center

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