Intensive Treatment For T-CELL Acute Lymphoblastic Leukemia and Advanced Stage Lymphoblastic Non-Hodgkin's Lymphoma: A Pediatric Oncology Group Phase III Study
OBJECTIVES: I. Determine, in a randomized trial, the effectiveness of high-dose methotrexate
when added to a multiagent chemotherapy backbone (the Dana Farber Cancer Institute regimen,
protocol DFCI-87001) proven effective in T-cell acute lymphoblastic leukemia (T-ALL) and
advanced lymphoblastic non-Hodgkin's lymphoma (NHL). II. Determine the role of dexrazoxane
in preventing cardiotoxicity in children with T-ALL and advanced lymphoblastic NHL treated
with an anthracycline-based regimen. III. Study the biology of T-cell lymphoid malignancies
by accumulating data on the concurrent ALL classification study (POG-9400) and analyzing the
data relative to outcome. IV. Evaluate the correlation of minimal residual disease (using
the TAL 1 proto-oncogene) with event-free survival. V. Determine the role of p53 and p16
tumor suppressor genes in T-ALL. VI. Determine whether drug sensitivity profiles of blast
cells to doxorubicin, methotrexate, and cytarabine correlate with initial response and
subsequent relapse.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
disease category (acute lymphoblastic leukemia (ALL) with no CNS disease vs. ALL with CNS
disease vs. non-Hodgkin's lymphoma (NHL) with no CNS disease vs. NHL with CNS disease),
gender, race (Caucasian vs. African American vs. Hispanic). Patients are randomized to one
of four treatment arms. ARM I: During induction therapy, patients receive vincristine IV
once daily on days 1, 8, 15, and 22, oral prednisone three times a day on days 1-21,
doxorubicin IV daily on days 1, 2, and 22, methotrexate IV once, at least 8 hours after
doxorubicin on day 2, and oral mercaptopurine daily on days 22-35. Patients receive triple
intrathecal therapy (TIT) consisting of methotrexate, cytarabine, and hydrocortisone on
weeks 1, 3, 4, 5, and 6. Patients with CNS 2 or 3 disease receive TIT on week 2. During
weeks 7-33, patients receive consolidation therapy consisting of vincristine IV once every 3
weeks, oral prednisone three times a day over 5 days, every 3 weeks, doxorubicin IV once
every 3 weeks, oral mercaptopurine daily for 14 days, every 3 weeks, and asparaginase
intramuscularly (IM) weekly on weeks 7-26. Patients receive TIT on week 10 and 22 (on week
16 for patients with CNS 2 or 3 disease). Patients receive radiotherapy beginning on week
22. During weeks 34-108, patients receive continuation therapy consisting of vincristine IV
once every 3 weeks, oral prednisone three times a day over 5 days, every 3 weeks,
methotrexate IV or IM weekly (omitted during TIT) and oral mercaptopurine daily for 14 days,
every 3 weeks. Patients receive TIT on weeks 40, 58, 76, and 94. Arm II: Patients receive
induction therapy as in Arm I with an addition of dexrazoxane IV given prior to doxorubicin
on days 1, 2, and 22. Patients receive consolidation therapy as in Arm I with an addition of
dexrazoxane IV given prior to doxorubicin once every 3 weeks. Patients receive continuation
therapy as in Arm I. Arm III: Patients receive induction therapy as in Arm I in addition to
high dose methotrexate IV on week 4 and leucovorin calcium IV or orally every 6 hours for 7
doses beginning 36 hours after high dose methotrexate. Patients receive consolidation
therapy as in Arm I in addition to high dose methotrexate IV on weeks 7, 10, and 13 followed
by leucovorin calcium as in induction therapy. Patients receive continuation therapy as in
Arm I. Arm IV: Patients receive induction therapy and consolidation therapy as in Arms I,
II, and III. Patients receive continuation therapy as in Arm I. Treatment continues for up
to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients are
followed every 2 months for 1 year, every 4 months for 3 years, then every 6 months for 2
years.
PROJECTED ACCRUAL: A total of 494 patients will be accrued for this study.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Complete Continuous Remission
Since all patients receive the same induction, the endpoint will be CCR , i.e. complete continuous remission (the time to failure for any cause among patients achieving a complete response)
Time to failure for any cause among patients achieving a complete response
No
Barbara L. Asselin, MD
Study Chair
James P. Wilmot Cancer Center
United States: Federal Government
9404
NCT01230983
June 1996
October 2004
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