Treatment for Newly Diagnosed Patients With Stage III/IV Non-Hodgkin Lymphoma-Study XIII (A Therapeutic Pilot Study)

The overall objective of this research study is to determine the toxicity and feasibility of administration of an intensified, multi-agent chemotherapy regimen for children with stages III and IV non-Hodgkin lymphoma (NHL), lymphoblastic histiotype. The planned pilot therapy includes major modifications of our best previous treatments for patients with T-cell acute lymphoblastic leukemia (ALL) that may improve the disease-free survival of these children and adolescents. Ultimately, it is intended to propose this therapy for further evaluation in the setting of a patient population large enough to evaluate its efficacy.

Secondary objectives are:

• To determine the toxicity of high-dose methotrexate (HDMTX) given prior to the induction/consolidation phase of therapy and of repeated induction treatment (weeks 16-21) in patients with advanced stage NHL, lymphoblastic histiotype.
• To determine the toxicity and feasibility of administration of continuation therapy which include additional drug pairs not used in the St. Jude Total XI-ALL study.
• To estimate the complete response (CR) rate and event-free survival (EFS) in children with stage III/IV lymphoblastic NHL after treatment with this intensified multiagent chemotherapy. Pooling of data from this study with that gained from treatment of patients with T-ALL on the Total XIII and XIII B studies, with appropriate stratification, will facilitate this aim.
• To compare plasma and cerebrospinal fluid concentrations of VP-16 after 1 hour of administration. The data obtained here will be pooled for analysis with that from Total XIII and Total XIII B studies
• To assess serially whether the frequency of specific HPRT mutations in are related to cumulative dose of etoposide, or plasma AUC of etoposide, etoposide catechol, or both
• To assess the degree of bone marrow infiltration at the time of diagnosis and serially during remission using and comparing morphologic, immunologic and molecular methods. In the absence of morphologically detected tumor cells, we will estimate the frequency of minimal residual disease (MRD) during remission using immunologic and molecular methods. The data obtained here will be pooled for analysis with that obtained from T-cell ALL cases treated on Total XIII and Total XIII B ALL studies.
• Because similar studies are being conducted for patients with T-ALL on the Total XIII and Total XIII B ALL studies, we will pool data from the present study with that from T-cell ALL cases treated on Total XIII and Total XIII B ALL studies and correlate detection of lymphoblasts in bone marrow or cerebrospinal fluid (CSF) with subsequent clinical course (complete remission duration).
• To evaluate the sensitivity of neoplastic cells at diagnosis to anticancer drugs. This evaluation will be limited to patients with bone marrow involvement or viable tumor samples at diagnosis. Information obtained from this aim will complement that obtained from patients with T-ALL in the Total XIII and Total XIII B ALL studies.

Details of Treatment Plan:

Pre-Induction Chemotherapy