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

Primary Purpose

B-cell Childhood Acute Lymphoblastic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ifosfamide
etoposide
rituximab
carboplatin
filgrastim
methotrexate
cytarabine
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Childhood Acute Lymphoblastic Leukemia

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, rituximab)

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate determined by physical exam and appropriate imaging studies
Response rates and confidence intervals will be constructed according to the method of Chang and O'Brien.
Relapse-free survival rate
Estimated by the Kaplan-Meier method.
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

Secondary Outcome Measures

CD34 cells mobilization by flow cytometry

Full Information

First Posted
April 7, 2003
Last Updated
October 7, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00058461
Brief Title
Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Terminated
Study Start Date
November 2003 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, rituximab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
Given IT
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
Given IT
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response rate determined by physical exam and appropriate imaging studies
Description
Response rates and confidence intervals will be constructed according to the method of Chang and O'Brien.
Time Frame
Up to 3 years
Title
Relapse-free survival rate
Description
Estimated by the Kaplan-Meier method.
Time Frame
Up to 3 years
Title
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
CD34 cells mobilization by flow cytometry
Time Frame
At the completion of 2 courses of treatment

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Griffin
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Arcadia
State/Province
California
ZIP/Postal Code
91006-3776
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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