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.
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
Drug | Synonyms | Arms |
---|
Daunorubicin | DNR | LR |
Prednisolone | Pred | LR |
Vincristine | VCR | LR |
Epirubicin | EPI | LR |
E-coli L-asparaginase | E-coli L-Asp | LR |
6-Mercaptopurine | 6-MP | LR |
Methotrexate | MTX | LR |
Hydrocortisone | | LR |
Cytarabine | Ara-C | SR |
Cyclophosphamide | Cy | SR |
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
Name | Type | Description | Interventions |
---|
SR | Experimental | 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. | - Daunorubicin
- Prednisolone
- Vincristine
- Epirubicin
- E-coli L-asparaginase
- 6-Mercaptopurine
- Methotrexate
- Hydrocortisone
- Cytarabine
- Cyclophosphamide
|
LR | Experimental | 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. | - 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 |
Last Updated
June 11, 2021