Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia

Basic Trial Information

Objectives

1. 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.
2. Determine the relapse-free survival rate of patients treated with this regimen.
3. 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.
4. Determine whether this regimen plus filgrastim (G-CSF) will result in mobilization of greater than 2 X 10⁶/kg peripheral blood stem cells (CD34+ cells, PBSC) in at least 80% of patients for whom peripheral stem cell collection is performed.
5. Determine the time course of engraftment for patients who undergo peripheral stem cell transplantation after collection of stem cells using this mobilization regimen.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• 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

Chemotherapy

• More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
• No other concurrent chemotherapy

Endocrine therapy

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

Radiotherapy

• 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

Surgery

• Not specified

Other

• Recovered from prior therapy
• No concurrent participation in another phase II study

Patient Characteristics:

Age

• 21 or under when diagnosed with recurrent or refractory disease

Performance status

• ECOG 0-2

Life expectancy

• At least 2 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm³*
• Platelet count ≥ 100,000/mm³ (transfusion independent)*
• Hemoglobin ≥ 10.0 g/dL (RBC transfusion allowed)*

 [Note: *Patients with B-cell acute lymphoblastic leukemia and lymphoma involving bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia are eligible but are not evaluable for hematologic toxicity]

Hepatic

• Bilirubin ≤ 1.5 times normal
• ALT < 2.5 times normal

Renal

• No chronic renal insufficiency
  • Renal insufficiency allowed provided it is secondary to tumor lysis syndrome

Other

• 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

Expected Enrollment

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

Outcomes

Response
Relapse-free survival rate
Toxicity
Mobilization
Time course of engraftment

Outline

This is a multicenter study. Patients are stratified by disease (B-cell large cell lymphoma or atypical precursor B-cell lmphoblastic 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.

Griffin TC, Weitzman S, Weinstein H, et al.: A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 52 (2): 177-81, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Timothy Griffin, MD, Protocol chair(Contact information may not be current)		Ph: 682-885-4000

Registry Information
Official Title		A Phase II Study Of Rituximab And ICE Chemotherapy In Children With Recurrent/Refractory B-Cell (CD20+) Non-Hodgkin Lymphoma And B-Cell Acute Lymphoblastic Leukemia
Trial Start Date		2003-11-03
Trial Completion Date		2007-03-30
Registered in ClinicalTrials.gov		NCT00058461
Date Submitted to PDQ		2003-03-03
Information Last Verified		2010-11-18
NCI Grant/Contract Number		CA98543

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