Trial Information

LSA5 PROTOCOL FOR THE TREATMENT OF ADVANCED PEDIATRIC AND ADOLESCENT NON-HODGKIN'S LYMPHOMA (NHL)

OBJECTIVES: I. Assess the feasibility of treating all histologic subgroups of pediatric
non-Hodgkin's lymphoma on one protocol, with the addition of asparaginase during the
induction and consolidation phases for diffuse lymphoblastic lymphoma and T-cell, large
noncleaved cell diffuse lymphoma. II. Assess whether intensification of cyclophosphamide
during induction therapy will achieve a complete response rate of 95% in 1 to 1.5 months for
all histologies. III. Assess whether achieving remission induction in 1 month, administering
cytarabine/methotrexate by continuous infusion during consolidation therapy, and increasing
the number of intrathecal methotrexate injections throughout protocol therapy decreases
central nervous system relapse in these patients. IV. Assess whether a 5-year
recurrence-free survival of 85% is achievable for all histologies on this protocol. V.
Assess whether duration of maintenance chemotherapy may be stratified by stage and histology
of disease to avoid unnecessarily prolonged chemotherapy.

OUTLINE: The following acronyms are used: ARA-C Cytarabine, NSC-63878 ASP Asparaginase,
NSC-109229 CF Leucovorin, NSC-3590 CTX Cyclophosphamide, NSC-26271 DM Dexamethasone,
NSC-34521 DNR Daunorubicin, NSC-82151 G-CSF Granulocyte Colony-Stimulating Factor,
NSC-614629 LBL Lymphoblastic Lymphoma LCALKi1B Large Cell Anaplastic B-cell Lymphoma
LCALKi1T Large Cell Anaplastic T-cell Lymphoma LCL Large Cell Lymphoma Mesna Mercaptoethane
Sulfonate, NSC-113891 MTX Methotrexate, NSC-740 TMP-SMX Trimethoprim-Sulfamethoxazole VCR
Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 Induction: 2-Drug Combination Systemic
Chemotherapy plus Single-Agent Intrathecal Chemotherapy followed by 2- or 3-Drug Combination
Systemic Chemotherapy plus Single-Agent Intrathecal Chemotherapy. Part I: CTX/DNR; plus IT
ARA-C; followed by Part II: DM/VCR; plus ASP for patients with LBL, T-cell LCL, or LCALKi1T;
plus IT MTX. Consolidation: 2- or 3-Drug Combination Systemic Chemotherapy with Leucovorin
Rescue followed by 2- or 3-Drug Combination Systemic Chemotherapy. Part I: ARA-C/MTX with
CF; plus ASP for patients with LBL, T-cell LCL, or LCALKi1T; followed by Part II:
ARA-C/VP-16; plus, for patients with LBL, T-cell LCL, or LCALKi1T. Maintenance. Single-Agent
Systemic Chemotherapy with Leucovorin Rescue plus Single-Agent Intrathecal Chemotherapy
followed sequentially by 3 2-Drug Combination Systemic Chemotherapy Regimens. Part I: MTX;
with CF; plus IT MTX; followed by Part II: CTX/VCR; followed by Part III: ARA-C/VP-16;
followed by Part IV: DNR/DM.

PROJECTED ACCRUAL: 25 patients/stratum are expected to be accrued over 3 years. This study
will be reviewed for early closure if more than 1 patient has PD.