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Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Primary Purpose

Anaplastic Large Cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
etoposide
iodine I 131 tositumomab
quality-of-life assessment
peripheral blood stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anaplastic Large Cell Lymphoma

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have a histologically confirmed diagnosis of lymphoma expressing the cluster of differentiation (CD)20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) in accordance with current transplant standard of care for these patients Note: Patients with clinically non-transformed follicular lymphomas do not require repeat biopsies for immunophenotyping since these tumors are uniformly reactive with the tositumomab antibody Patients must have tumor burdens < 500cc by computed tomography (CT) or magnetic resonance (MRI) volumetric measurements and must not have splenomegaly at the time of enrollment; splenomegaly will be defined as a spleen volume > 2 standard deviations of the mean spleen volume to body weight ratio (mean = 3.84 cc/kg, SD = 1.53 cc/kg); thus, patients with > 6.9cc/kg will be defined as having splenomegaly; patients with splenomegaly that is thought to be due to G CSF/GM-CSF effect and not due to lymphomatous involvement of the spleen can been deemed eligible with the approval of an investigator Patients must have normal renal function (creatinine [Cr] < 2.0) Patients must have normal hepatic function (bilirubin < 1.5mg/dL), with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5mg/dL All patients eligible for therapeutic study must have autologous hematopoietic stem cells (2 x 10^6 CD34+ cells/kg) harvested and cryopreserved Patients must have an expected survival of > 60 days and must be free of major infection Exclusion Criteria: Circulating anti-mouse antibody (HAMA) Systemic anti-lymphoma therapy given within 30 days prior to anticipated treatment date Inability to understand or give an informed consent Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, or over 25% of red marrow) Central nervous system lymphoma Other serious medical conditions considered to represent contraindications to autologous stem cell transplant (ASCT) (e.g., active coronary artery disease, pulmonary dysfunction [forced expiratory volume in 1 second (FEV1) < 70% expected, Vital Capacity < 70% expected, diffusing capacity of the lung for carbon monoxide (DLCO) < 50%, patient on supplemental oxygen], AIDS, etc.) Pregnancy Prior bone marrow or stem cell transplant Presence of circulating lymphoma cells by morphology or flow cytometry (>= 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSC are to be used Southwest Oncology Group (SWOG) performance status >= 2.0 Unable to perform self-care during radiation isolation Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma (ineligible because these tumors express very low surface densities of CD20)

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (radio labeled monoclonal antibody, chemotherapy)

Arm Description

RADIOIMMUNOTHERAPY: Patients receive a test dose of iodine I 131 tositumomab IV on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over approximately 40-60 minutes on day -14 and are entered into radiation isolation until day -4. CHEMOTHERAPY: Patients receive etoposide IV on day -4 and cyclophosphamide IV on day -2. AUTOLOGOUS STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplantation on day 0.

Outcomes

Primary Outcome Measures

Progression-free Survival
Kaplan-Meier estimate of progression-free survival at 3 years will be used as the primary determinant of potential efficacy.

Secondary Outcome Measures

5 Year Overall Survival
Survival will be estimated using the method of Kaplan and Meier. Associated confidence intervals will be provided as part of the analysis.
Response Rate
Response rates will be estimated as the percentage of patients
Toxicity as Assessed by Common Terminology Criteria (CTC) v 2.0
Grade 3-4 Bearman non-hematologic toxicity will be carefully monitored throughout this study. The protocol will be terminated due to safety concerns if there exists sufficient evidence suggesting that the true rate of grade 3-4 nonhematologic toxicity exceeds 25%. All patients, regardless of histology, will be evaluated together for purposes of toxicity. Sufficient evidence will be taken to be a lower limit to the appropriate 90% one-sided confidence interval in excess of 25%

Full Information

First Posted
December 10, 2003
Last Updated
July 21, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00073918
Brief Title
Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
A Phase II Trial Evaluating The Efficacy of Radioiodinated Tositumomab (Anti-CD20) Antibody, Etoposide and Cyclophosphamide Followed by Autologous Transplantation, for Relapsed or Refractory Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
February 1999 (undefined)
Primary Completion Date
October 2, 2011 (Actual)
Study Completion Date
October 2, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial is studying how well giving iodine I 131 tositumomab together with etoposide and cyclophosphamide followed by autologous stem cell transplant works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Combining a radiolabeled monoclonal antibody with combination chemotherapy before autologous stem cell transplant may kill more cancer cells
Detailed Description
PRIMARY OBJECTIVES: I. To assess the progression-free survival of patients receiving 131 I labeled tositumomab antibody, etoposide (VP-16) and cyclophosphamide (CY) followed by autologous transplantation. II. To examine the potential efficacy of 131 I labeled tositumomab antibody, etoposide (VP-16) and cyclophosphamide (CY) followed by autologous transplantation. SECONDARY OBJECTIVES: I. To assess the overall survival of patients receiving 131 I labeled tositumomab antibody, etoposide (VP-16) and cyclophosphamide (CY) followed by autologous transplantation. II. To evaluate the toxicity and tolerability of the above therapy. OUTLINE: RADIOIMMUNOTHERAPY: Patients receive a test dose of iodine I 131 tositumomab intravenously (IV) on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over approximately 40-60 minutes on day -14 and are entered into radiation isolation until day -4. CHEMOTHERAPY: Patients receive etoposide IV on day -4 and cyclophosphamide IV on day -2. AUTOLOGOUS STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. After completion of study treatment, patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaplastic Large Cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Splenic Marginal Zone Lymphoma, Waldenström Macroglobulinemia

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Treatment (radio labeled monoclonal antibody, chemotherapy)
Arm Type
Experimental
Arm Description
RADIOIMMUNOTHERAPY: Patients receive a test dose of iodine I 131 tositumomab IV on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over approximately 40-60 minutes on day -14 and are entered into radiation isolation until day -4. CHEMOTHERAPY: Patients receive etoposide IV on day -4 and cyclophosphamide IV on day -2. AUTOLOGOUS STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplantation on day 0.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
iodine I 131 tositumomab
Other Intervention Name(s)
131-I-anti-B1 antibody, 131-I-anti-B1 monoclonal antibody, I131-MOAB-B1, iodine I 131 MOAB anti-B1, iodine I 131 monoclonal antibody anti-B1
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Other Intervention Name(s)
quality of life assessment
Intervention Description
Ancillary study
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo ASCT given via central catheter
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
Kaplan-Meier estimate of progression-free survival at 3 years will be used as the primary determinant of potential efficacy.
Time Frame
At year 3
Secondary Outcome Measure Information:
Title
5 Year Overall Survival
Description
Survival will be estimated using the method of Kaplan and Meier. Associated confidence intervals will be provided as part of the analysis.
Time Frame
Up to 15 years
Title
Response Rate
Description
Response rates will be estimated as the percentage of patients
Time Frame
From date of transplant through date of relapse/progression or death, assessed up to 15 years
Title
Toxicity as Assessed by Common Terminology Criteria (CTC) v 2.0
Description
Grade 3-4 Bearman non-hematologic toxicity will be carefully monitored throughout this study. The protocol will be terminated due to safety concerns if there exists sufficient evidence suggesting that the true rate of grade 3-4 nonhematologic toxicity exceeds 25%. All patients, regardless of histology, will be evaluated together for purposes of toxicity. Sufficient evidence will be taken to be a lower limit to the appropriate 90% one-sided confidence interval in excess of 25%
Time Frame
From date of first exposure to study drug, through date of relapse/progression or other significant medical event confounding further assessment, assessed up to 15 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a histologically confirmed diagnosis of lymphoma expressing the cluster of differentiation (CD)20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) in accordance with current transplant standard of care for these patients Note: Patients with clinically non-transformed follicular lymphomas do not require repeat biopsies for immunophenotyping since these tumors are uniformly reactive with the tositumomab antibody Patients must have tumor burdens < 500cc by computed tomography (CT) or magnetic resonance (MRI) volumetric measurements and must not have splenomegaly at the time of enrollment; splenomegaly will be defined as a spleen volume > 2 standard deviations of the mean spleen volume to body weight ratio (mean = 3.84 cc/kg, SD = 1.53 cc/kg); thus, patients with > 6.9cc/kg will be defined as having splenomegaly; patients with splenomegaly that is thought to be due to G CSF/GM-CSF effect and not due to lymphomatous involvement of the spleen can been deemed eligible with the approval of an investigator Patients must have normal renal function (creatinine [Cr] < 2.0) Patients must have normal hepatic function (bilirubin < 1.5mg/dL), with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5mg/dL All patients eligible for therapeutic study must have autologous hematopoietic stem cells (2 x 10^6 CD34+ cells/kg) harvested and cryopreserved Patients must have an expected survival of > 60 days and must be free of major infection Exclusion Criteria: Circulating anti-mouse antibody (HAMA) Systemic anti-lymphoma therapy given within 30 days prior to anticipated treatment date Inability to understand or give an informed consent Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, or over 25% of red marrow) Central nervous system lymphoma Other serious medical conditions considered to represent contraindications to autologous stem cell transplant (ASCT) (e.g., active coronary artery disease, pulmonary dysfunction [forced expiratory volume in 1 second (FEV1) < 70% expected, Vital Capacity < 70% expected, diffusing capacity of the lung for carbon monoxide (DLCO) < 50%, patient on supplemental oxygen], AIDS, etc.) Pregnancy Prior bone marrow or stem cell transplant Presence of circulating lymphoma cells by morphology or flow cytometry (>= 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSC are to be used Southwest Oncology Group (SWOG) performance status >= 2.0 Unable to perform self-care during radiation isolation Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma (ineligible because these tumors express very low surface densities of CD20)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay Gopal
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

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