ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

National Hospital Organization Nagoya Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Down Syndrome; Childhood Cancer; Acute Lymphoblastic Leukemia

Treatments: Drug: Cytarabine; Drug: Methotrexate; Drug: E-coli L-asparaginase; Drug: Hydrocortisone; Drug: Prednisolone; Drug: Epirubicin; Drug: Daunorubicin; Drug: Cyclophosphamide; Drug: 6-Mercaptopurine; Drug: Vincristine

Study type: Interventional

Funder types: Other

Identifiers

NCT03286634

ASIA-DS-ALL-2016

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: Under 20 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

SR

Experimental group

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.

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide

Drug: 6-Mercaptopurine

Drug: Daunorubicin

Drug: Epirubicin

Drug: Prednisolone

Drug: Methotrexate

Drug: E-coli L-asparaginase

Drug: Hydrocortisone

Drug: Cytarabine

LR

Experimental group

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.

Treatment:

Drug: Vincristine

Drug: 6-Mercaptopurine

Drug: Daunorubicin

Drug: Epirubicin

Drug: Prednisolone

Drug: Methotrexate

Drug: E-coli L-asparaginase

Drug: Hydrocortisone