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Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia
This study has been completed.

First Received on April 7, 2003.   Last Updated on December 16, 2010   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00058461
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carboplatin
Drug: cytarabine
Drug: etoposide
Drug: ifosfamide
Drug: methotrexate
Phase II

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response [ Designated as safety issue: No ]
  • Relapse-free survival rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Mobilization [ Designated as safety issue: No ]
  • Time course of engraftment [ Designated as safety issue: No ]

Study Start Date: November 2003
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

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

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

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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/mm^3*
  • Platelet count ≥ 100,000/mm^3 (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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00058461

  Show 129 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Timothy C. Griffin, MD Cook Children's Medical Center - Fort Worth
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00058461     History of Changes
Other Study ID Numbers: CDR0000298751, COG-ANHL0121
Study First Received: April 7, 2003
Last Updated: December 16, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent childhood large cell lymphoma
B-cell childhood acute lymphoblastic leukemia
childhood diffuse large cell lymphoma
recurrent childhood small noncleaved cell lymphoma
childhood immunoblastic large cell lymphoma
L3 childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
Burkitt lymphoma

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Methotrexate
Isophosphamide mustard
Rituximab
Etoposide
Ifosfamide
Carboplatin
Lenograstim
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012