(POG-ALINC-16-/HR)

Phase III Randomized Study of High Versus Standard Dose Methotrexate and High Dose Cytarabine and Asparaginase Rescue Versus Standard Dose Cytarabine and Teniposide During Intensive Continuation and Consolidation in Children with High Risk Acute Lymphocytic Leukemia: An ALinC #16 Study.

This trial on the cancer.gov site.

Treatment for high-risk ALL, defined as

• B-precursor or B-cell ALL
• no L3 B-cell ALL
• at least 1 of the following poor-risk factors:
  • CNS involvement (5 or more WBC/microliter and leukemic blasts on cytospin)
  • cranial nerve palsy, eye involvement, or parenchymal disease in the brain or spinal cord
  • testicular involvement
  • presence of t(1;19), t(4,11), or t(9;22)
  • age at dx 10-21 and/or WBC at dx 50,000 or greater and either absence of trisomies 4 and 10 or DNA index no greater than 1.16

Protocol initiated: (?), 540 patients over approximately 3.8 years

Study Chair: Joanne Kurtzberg 919-684-8963

Specific Aims:

• higher vs standard dose methotrexate (2.5 vs 1 g/sqm) during intensive continuation/consolidation
• compare these same endpoints in patients treated with pulses of high-dose ara C with asparaginase rescue vs standard dose are C/teniposide during intensive continuation/consolidation therapy

Also:

• correlate laboratory and clinical prognostic variables with the other POG studies
• identify patients at risk of treatment failure through in vitro surdies of lymphoblast methotrexate and MP metabolism an dthrough erythrocyte drug and enzyme levels
• assess the prognostic significance of marrow blasts at 2 weeks
• correlate elevation of transaminases with treatment outcome
• assess ASP-related toxicities and anti-ASP antibody formation in patients treated with standard ASP during remission induction and with PEG-ASP during intensified continuatio/consolidation therapy (not at all institutions)

Protocol outline:

• Following induction, patients with M1 maroow are randomized on regimens A-D [note: t 4 11) 9-22) go to A]
• Patients who remain in remission after consolidation go to continuation.
• Patients with CNS involvement at dx receive additional doses of TIT during induction an
• those with CNS also recieve radiation after 1 year of treatment

4 arms of treatment:

• A: control regimen, std methotrexate and ara C
• B: std methotrexate, high dose ara C
• C: high dose methotrexate and std ara C
• D: high dose methotrexate and high dose ara C/PEG-asparaginase

POG 9406

• X weeks induction
  • four drug combination systemic chemo and three drug IT
    • vincristine
    • prednisone
    • daunorubiin
    • asparaginase
    • triple IT, TIT (intraethical ara C, methotrexate, hydrocortisone)
• X weeks continuation/consolidation
  • A: std methotrexate and std ara C, alternating the following:
    • methotrexate (leucovorin rescue)/6-MP
    • ara C/teniposide
    • daunorubicin/ara C/vincristine/prednisone/PEG-ASP
    • plus TIT
  • B: std methotrexate, high dose ara C, alternating the following:
    • methotrexate (leucovorin rescue)/6-MP
    • high-dose ara C/PEG-ASP
    • daunorubicin/ara C/vincristine/prednisone/PEG-ASP
    • plus TIT
  • C: high dose methotrexate and std ara C, alternating
    • high dose methotrexate (leucovorin rescue)/6-MP
    • ara C/teniposide
    • daunorubicin/ara C/vincristine/prednisone/PEG asparaginase
    • plus TIT
  • D: high dose methotrexate and high dose ara C/PEG-asparaginase, alternating the following:
    • high dose methotrexate(leucovorin rescue)/6-MP
    • high dose ara C/PEG asparaginase
    • daunorubicin/ara C/vincristine/prednisone/PEG-asparaginase
• X weeks Continuation
  • two drug combination systemic chemotherapy plus TIT
    • methotrexate/6-MP
    • TIT

Notes:

Compared with the current CCG higher risk protocol (CCG 1961), POG 9406 utilizes the following not in the CCG trial:

• leucovorin rescue after methotrexate treatment (but, CCG uses oral methotrexate, not IV)
• PEG asparaginase in all arms of trial
• no cytoxin
• all use teniposide (a topoisomerase inhibitor)
• TIT