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Iodine I 131 Tositumomab Followed by Autologous Stem Cell Transplantation in Treating Older Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
sargramostim
autologous bone marrow transplantation
peripheral blood stem cell transplantation
tositumomab and iodine I 131 tositumomab
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt 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

Eligibility Criteria

60 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma CD20+ disease Failed at least 1 prior standard systemic therapy Persistent lymphoma by physical examination, radiographic studies, bone marrow evaluations, flow cytometry, or polymerase chain reaction Tumor burden less than 500 cc by computed tomography or MRI No splenomegaly Autologous hematopoietic stem cells or bone marrow harvested and cryopreserved No circulating lymphoma cells by morphology or flow cytometry at or near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSCs are to be used 10% or less marrow involvement by flow cytometry or morphology if purged bone marrow is to be used No CNS lymphoma No chronic lymphocytic leukemia or small lymphocytic lymphoma/well-differentiated lymphocytic lymphoma PATIENT CHARACTERISTICS: Age 60 to 80 Performance status SWOG 0-1 Life expectancy More than 60 days Hematopoietic See Disease Characteristics Hepatic Bilirubin less than 1.5 mg/dL Renal Creatinine less than 2.0 mg/dL Cardiovascular No active coronary artery disease Pulmonary FEV_1 at least 70% of expected Vital capacity at least 70% of expected Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative Able to perform self-care during radiation isolation No major organ dysfunction No major infection No circulating anti-mouse antibody No other serious medical condition considered to represent contraindications to bone marrow transplantation No competing causes of death that would predict life span to be less than 10 additional years PRIOR CONCURRENT THERAPY: Biologic therapy No prior bone marrow or stem cell transplantation Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy No prior radiotherapy greater than 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, or more than 25% of red marrow) Surgery Not specified Other More than 30 days since prior systemic antilymphoma therapy

Sites / Locations

  • Fred Hutchinson Cancer Research Center

Outcomes

Primary Outcome Measures

Disease-free survival measured continuously

Secondary Outcome Measures

Full Information

First Posted
December 10, 2003
Last Updated
February 3, 2015
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00073931
Brief Title
Iodine I 131 Tositumomab Followed by Autologous Stem Cell Transplantation in Treating Older Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
A Phase II Trial Evaluating: Radioiodinated Anti-B1 (Anti-CD20) Antibody With Autologous Stem Cell Transplantation For Relapsed Or Refractory Non-Hodgkin's Lymphoma In Patients 60 Years Of Age And Older
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
October 1999 (undefined)
Primary Completion Date
May 2007 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Combining a radiolabeled monoclonal antibody with autologous stem cell transplantation may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: Phase II trial to study the effectiveness of combining iodine I 131 tositumomab with autologous stem cell transplantation in treating older patients who have relapsed or refractory non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES: Primary Determine the progression-free survival of older patients with relapsed or refractory non-Hodgkin's lymphoma treated with iodine I 131 tositumomab followed by autologous stem cell transplantation. Secondary Determine the overall survival of patients treated with this regimen. Determine the toxicity and tolerability of this regimen in these patients. OUTLINE: Radioimmunotherapy: Patients receive a test dose of iodine I 131 tositumomab on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over 1 hour on day -14 and are entered into radiation isolation until day -4. Autologous stem cell transplantation: Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients undergoing bone marrow transplantation receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 0 and continuing until blood counts recover. Patients are followed at 1, 3, 6, and 12 months and then annually thereafter. PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt 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

7. Study Design

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

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
5 µg/kg/day subcutaneously
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF
Intervention Description
250µg/m2/d subcutaneously
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Description
autologous stem cells given via central catheter
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
autologous stem cells given via central catheter
Intervention Type
Radiation
Intervention Name(s)
tositumomab and iodine I 131 tositumomab
Intervention Description
given intravenously (test dose of 1.7-10 mg/kg tositumomab antibody radiolabeled with ~10 mCi I-131) or via central catheter (therapy dose of 1.7-10 mg/kg tositumomab radiolabeled with individually calculated therapy dose of I-131)
Primary Outcome Measure Information:
Title
Disease-free survival measured continuously
Time Frame
from date of transplant through date of death

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma CD20+ disease Failed at least 1 prior standard systemic therapy Persistent lymphoma by physical examination, radiographic studies, bone marrow evaluations, flow cytometry, or polymerase chain reaction Tumor burden less than 500 cc by computed tomography or MRI No splenomegaly Autologous hematopoietic stem cells or bone marrow harvested and cryopreserved No circulating lymphoma cells by morphology or flow cytometry at or near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSCs are to be used 10% or less marrow involvement by flow cytometry or morphology if purged bone marrow is to be used No CNS lymphoma No chronic lymphocytic leukemia or small lymphocytic lymphoma/well-differentiated lymphocytic lymphoma PATIENT CHARACTERISTICS: Age 60 to 80 Performance status SWOG 0-1 Life expectancy More than 60 days Hematopoietic See Disease Characteristics Hepatic Bilirubin less than 1.5 mg/dL Renal Creatinine less than 2.0 mg/dL Cardiovascular No active coronary artery disease Pulmonary FEV_1 at least 70% of expected Vital capacity at least 70% of expected Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception HIV negative Able to perform self-care during radiation isolation No major organ dysfunction No major infection No circulating anti-mouse antibody No other serious medical condition considered to represent contraindications to bone marrow transplantation No competing causes of death that would predict life span to be less than 10 additional years PRIOR CONCURRENT THERAPY: Biologic therapy No prior bone marrow or stem cell transplantation Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy No prior radiotherapy greater than 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, or more than 25% of red marrow) Surgery Not specified Other More than 30 days since prior systemic antilymphoma therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay K. Gopal, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17312330
Citation
Gopal AK, Rajendran JG, Gooley TA, Pagel JM, Fisher DR, Petersdorf SH, Maloney DG, Eary JF, Appelbaum FR, Press OW. High-dose [131I]tositumomab (anti-CD20) radioimmunotherapy and autologous hematopoietic stem-cell transplantation for adults > or = 60 years old with relapsed or refractory B-cell lymphoma. J Clin Oncol. 2007 Apr 10;25(11):1396-402. doi: 10.1200/JCO.2006.09.1215. Epub 2007 Feb 20.
Results Reference
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Iodine I 131 Tositumomab Followed by Autologous Stem Cell Transplantation in Treating Older Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

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