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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00058461
First received: April 7, 2003
Last updated: October 7, 2013
Last verified: October 2013
  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. 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.


Condition Intervention Phase
B-cell Childhood Acute Lymphoblastic Leukemia
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
L3 Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Drug: ifosfamide
Drug: etoposide
Biological: rituximab
Drug: carboplatin
Biological: filgrastim
Drug: methotrexate
Drug: cytarabine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Rituximab (IND #7028) and Ifosfamide, Carboplatin and Etoposide (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 rate determined by physical exam and appropriate imaging studies [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Response rates and confidence intervals will be constructed according to the method of Chang and O'Brien.

  • Relapse-free survival rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated by the Kaplan-Meier method.

  • Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • CD34 cells mobilization by flow cytometry [ Time Frame: At the completion of 2 courses of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 82
Study Start Date: November 2003
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, rituximab)
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.
Drug: ifosfamide
Given IV
Drug: etoposide
Given IV
Biological: rituximab
Given IV
Drug: carboplatin
Given IV
Biological: filgrastim
Given SC
Drug: methotrexate
Given IT
Drug: cytarabine
Given IT
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Timothy Griffin Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00058461     History of Changes
Other Study ID Numbers: NCI-2012-01804, NCI-2012-01804, COG-ANHL0121, CDR0000298751, ANHL0121, ANHL0121, U10CA098543
Study First Received: April 7, 2003
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Non-Hodgkin
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases
Carboplatin
Cytarabine
Etoposide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Methotrexate
Rituximab
Abortifacient Agents

ClinicalTrials.gov processed this record on October 23, 2014