Back to resultsIodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma
Primary Purpose
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
peripheral blood stem cell transplantation
iodine I 131 tositumomab
laboratory biomarker analysis
flow cytometry
polymerase chain reaction
Sponsored by
About this trial
This is an interventional treatment trial for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Eligibility Criteria
Inclusion Criteria: Patients must have a histologically confirmed diagnosis of lymphoma expressing the CD20 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 Creatinine (Cr) < 2.0 Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, whom may have a total bilirubin above 1.5 mg/dL All patients eligible for therapeutic study must have (>= 2x10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved, or this number of cells harvested from a syngeneic donor Patients must have an expected survival of > 60 days and must be free of major infection DONOR: Syngeneic donors must be confirmed syngeneic by ABO typing, human leukocyte antigen (HLA) typing, and variable number tandem repeat (VNTR) analysis DONOR: Syngeneic donors must meet eligibility under Standard Practice Guidelines/Standard Treatment Exclusion Criteria: Circulating anti-mouse antibody (HAMA) (to be determined before both dosimetry and therapy) Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose Inability to understand or give an informed consent Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, > 25% of red marrow) Central nervous system lymphoma Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusing capacity (DLCO) < 50% predicted, patient on supplemental oxygen, acquired Immunodeficiency syndrome [AIDS], etc.) Pregnancy Prior bone marrow or stem cell transplant South West Oncology Group (SWOG) performance status >= 2 Unable to perform self-care during radiation isolation Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (chemoradioimmunotherapy)
Arm Description
Patients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV QD on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.
Outcomes
Primary Outcome Measures
Maximum tolerated dose/dose limiting toxicity
Assessed according to Bearman scale for Regimen-Related Toxicities.
Secondary Outcome Measures
Overall and progression-free survival rate
Response rate
Toxicity/tolerability of study regimen
Type, frequency, and severity of adverse events grade 3 and above (assessed by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3.0.
Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy
Ability to administer complete course of I 131-tositumomab and fludarabine phosphate as descried in protocol.
Full Information
NCT ID
NCT00110071
First Posted
May 3, 2005
Last Updated
August 4, 2014
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00110071
Brief Title
Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
A Clinical Trial Evaluating I131-Tositumomab (Anti-CD20) With Escalating Doses of Fludarabine Followed by Autologous or Syngeneic Stem Cell Transplantation for Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma in Patients 60 Years of Age and Older
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
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 I trial studies the side effects and best dose of fludarabine (fludarabine phosphate) when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous or syngeneic stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 tositumomab together with fludarabine followed by autologous stem cell transplant may be an effective treatment for NHL
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the maximally tolerated dose of fludarabine that can be combined with 131I-anti-CD20 (iodine I 131 tositumomab) delivering =< 27Gy to critical normal organs followed by autologous or syngeneic transplantation in patients >= 60 years of age with relapsed B-NHL.
SECONDARY OBJECTIVES:
I. To assess the overall and progression-free survival of the above regimen in such patients.
II. To evaluate the response rates of the above therapy.
III. To evaluate the toxicity and tolerability of the above therapy.
IV. To evaluate the feasibility of delivering concurrent high-dose radioimmunotherapy (RIT) and chemotherapy.
OUTLINE: This is a dose-escalation study of fludarabine phosphate as used in combination with I 131 tositumomab and stem cell transplant.
Patients receive a dosimetric dose of iodine I 131 tositumomab intravenously (IV) over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV once daily (QD) on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.
Patients with circulating lymphoma cells by peripheral smear receive tositumomab IV over 1 hour OR rituximab IV over 1 hour followed by tositumomab IV over 1 hour before the dosimetric iodine I 131 tositumomab infusion.
After completion of study treatment, patients are followed up 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
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 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (chemoradioimmunotherapy)
Arm Type
Experimental
Arm Description
Patients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV QD on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
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 transplantation (infusion of autologous or syngeneic PBSC via central line)
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 (dosimetric dose) or via central line (therapeutic dose)
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
polymerase chain reaction
Other Intervention Name(s)
PCR
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximum tolerated dose/dose limiting toxicity
Description
Assessed according to Bearman scale for Regimen-Related Toxicities.
Time Frame
Up to 30 days post-transplant
Secondary Outcome Measure Information:
Title
Overall and progression-free survival rate
Time Frame
Up to 6 years
Title
Response rate
Time Frame
Up to 12 months
Title
Toxicity/tolerability of study regimen
Description
Type, frequency, and severity of adverse events grade 3 and above (assessed by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3.0.
Time Frame
Through day 100 post-transplant
Title
Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy
Description
Ability to administer complete course of I 131-tositumomab and fludarabine phosphate as descried in protocol.
Time Frame
Through day -7 prior to transplant
10. Eligibility
Sex
All
Minimum 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 CD20 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
Creatinine (Cr) < 2.0
Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, whom may have a total bilirubin above 1.5 mg/dL
All patients eligible for therapeutic study must have (>= 2x10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved, or this number of cells harvested from a syngeneic donor
Patients must have an expected survival of > 60 days and must be free of major infection
DONOR: Syngeneic donors must be confirmed syngeneic by ABO typing, human leukocyte antigen (HLA) typing, and variable number tandem repeat (VNTR) analysis
DONOR: Syngeneic donors must meet eligibility under Standard Practice Guidelines/Standard Treatment
Exclusion Criteria:
Circulating anti-mouse antibody (HAMA) (to be determined before both dosimetry and therapy)
Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose
Inability to understand or give an informed consent
Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, > 25% of red marrow)
Central nervous system lymphoma
Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusing capacity (DLCO) < 50% predicted, patient on supplemental oxygen, acquired Immunodeficiency syndrome [AIDS], etc.)
Pregnancy
Prior bone marrow or stem cell transplant
South West Oncology Group (SWOG) performance status >= 2
Unable to perform self-care during radiation isolation
Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma
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
Citations:
PubMed Identifier
24530971
Citation
Gopal AK, Gooley TA, Rajendran JG, Pagel JM, Fisher DR, Maloney DG, Appelbaum FR, Cassaday RD, Shields A, Press OW. Myeloablative I-131-tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age >/= 60 years with B cell lymphoma. Biol Blood Marrow Transplant. 2014 Jun;20(6):770-5. doi: 10.1016/j.bbmt.2014.02.004. Epub 2014 Feb 12.
Results Reference
derived
Learn more about this trial
Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma
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