Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia
Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia
This phase II trial is studying how well rituximab together with ifosfamide, carboplatin, and
 etoposide works in treating young patients with recurrent or refractory non-Hodgkin's
 lymphoma or acute lymphoblastic leukemia. Chemotherapy drugs, such as ifosfamide,
 carboplatin, and etoposide, work in different ways to stop cancer cells from dividing so they
 stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and
 either kill them or deliver cancer-killing substances to them without harming normal cells.
 Combining ifosfamide, carboplatin, and etoposide with rituximab may kill more cancer cells.
PRIMARY OBJECTIVES:

 I. Determine the response of pediatric patients with relapsed or refractory B-cell
 non-Hodgkin's lymphoma or acute lymphoblastic leukemia treated with ifosfamide, carboplatin,
 and etoposide combined with rituximab.

 II. Determine the relapse-free survival rate of patients treated with this regimen.

 III. Determine the toxicity profile of this regimen in these patients, specifically the
 frequency of therapy delays between courses due to prolonged grade IV hematologic toxicity.

 SECONDARY OBJECTIVES:

 I. Determine whether this regimen plus filgrastim (G-CSF) will result in mobilization of
 greater than 2 X 10^6/kg peripheral blood stem cells (CD34+ cells, PBSC) in at least 80% of
 patients for whom peripheral stem cell collection is performed.

 II. Determine the time course of engraftment for patients who undergo peripheral stem cell
 transplantation after collection of stem cells using this mobilization regimen.

 OUTLINE: This is a multicenter study. Patients are stratified by disease (B-cell large cell
 lymphoma or atypical precursor B-cell lymphoblastic lymphoma vs small non-cleaved cell
 lymphoma or B-cell acute lymphoblastic leukemia).

 Patients receive ifosfamide IV over 2 hours and etoposide IV over 1 hour on days 3-5,
 rituximab IV on days 1 and 3, and carboplatin IV over 1 hour on day 3. Patients receive
 filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood
 counts recover. Patients also receive intrathecal (IT) chemotherapy comprising methotrexate
 and cytarabine. Patients with B-cell large cell lymphoma and negative CSF cytology receive IT
 chemotherapy on day 3 of the first course only. Patients with small non-cleaved cell lymphoma
 or B-cell acute lymphoblastic leukemia and negative CSF cytology receive IT chemotherapy on
 day 3. All patients with positive CSF cytology receive IT chemotherapy on days 3, 10, and 17
 of the first and second courses. Treatment repeats every 23 days for up to 3 courses in the
 absence of disease progression or unacceptable toxicity.

 Patients are followed for survival.

 PROJECTED ACCRUAL: A total of 42-82 patients (21-41 per disease stratum) will be accrued for
 this study within 2-4 years.
Inclusion Criteria:

 -  Histologically confirmed B-cell non-Hodgkin's lymphoma OR acute lymphoblastic leukemia

 -  CD20+ (confirmed by flow cytometry of tumor tissue, involved marrow, or CD20
 immunostaining)

 -  The following histologies are generally CD20+ and are eligible:

 -  Diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma,
 or follicular lymphoma, grade III (rare), documented by flow cytometry or
 appropriate immunohistochemistry, any stage

 -  Burkitt's lymphoma or atypical Burkitt's/Burkitt-like lymphoma, any stage

 -  B-cell acute lymphoblastic leukemia, with FABL3 morphology and/or
 demonstration of surface immunoglobin by flow cytometry

 -  Atypical precursor B-cell lymphoblastic lymphoma or other unusual
 histologies that are CD20+

 -  Measurable disease by clinical, radiographic, or histologic criteria

 -  Must be in first or later recurrence or have disease that is primarily refractory to
 conventional therapy

 -  No isolated CNS disease

 -  Performance status - ECOG 0-2

 -  At least 2 months

 -  Absolute neutrophil count ≥ 1,000/mm^3*

 -  Platelet count ≥ 100,000/mm^3 (transfusion independent)*

 -  Hemoglobin ≥ 10.0 g/dL (RBC transfusion allowed)*

 -  Bilirubin ≤ 1.5 times normal

 -  ALT < 2.5 times normal

 -  No chronic renal insufficiency

 -  Renal insufficiency allowed provided it is secondary to tumor lysis syndrome

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception during and for 3 months after study
 treatment

 -  HIV negative

 -  No active uncontrolled infection

 -  Seizure disorder allowed if well controlled with anticonvulsants

 -  No CNS toxicity greater than grade II

 -  At least 24 hours since prior growth factor(s)

 -  At least 60 days since prior biologic (antineoplastic) therapy

 -  Prior stem cell transplantation allowed provided the following criteria are met:

 -  More than 60 days since transplantation

 -  Hematopoietic lab value requirements are met (See Hematopoietic)

 -  No evidence of graft-versus-host disease (if post-allogeneic transplantation)

 -  Prior monoclonal antibody therapy allowed (including rituximab)

 -  No other concurrent immunomodulating agents

 -  More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)

 -  No other concurrent chemotherapy

 -  No concurrent steroids (except for rituximab infusion-related symptoms)

 -  At least 2 weeks since prior local palliative radiotherapy (small port)

 -  At least 6 weeks since prior substantial bone marrow radiotherapy

 -  At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more
 of the pelvis

 -  Concurrent radiotherapy to localized painful, airway-compromising, or other acute
 organ-threatening lesions allowed provided at least 1 measurable lesion is not
 irradiated

 -  Recovered from prior therapy

 -  No concurrent participation in another phase II study