Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy
Primary Purpose
Lymphoma, Non-Hodgkin
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bexxar (tositumomab)
External beam radiotherapy (XRT)
Potassium Iodide (KI)
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin
Eligibility Criteria
INCLUSION CRITERIA
- Histologically confirmed low grade CD20+ B cell non-Hodgkin lymphoma (NHL) patients who have relapsed after chemotherapy or are chemotherapy resistant and have one or more sites of disease measuring more than 5 cm.
- The patients must have failed at least one chemotherapy regimen
- No anticancer treatment for three weeks prior to study initiation (six weeks if Rituximab, nitrosourea or Mitomycin C)
- Fully recovered from all toxicities associated with prior surgery, radiation, chemotherapy or immunotherapy
- An institutional review board- (IRB)-approved signed informed consent
- Age 19 years or older
- Expected survival of at least 6 months
- Prestudy Performance Status of 0, 1 or 2 according to the World Health Organization (WHO)
- Absolute neutrophil count (ANC) of at least 1,500/mm³
- Platelet count at least 100,000/mm³
- Hct > 30%
- Hgb > 9.0 gm
- Bilirubin ≤ 2.0
- Creatinine ≤ 2.0
- Bone marrow involvement with lymphoma less than 25% (bilateral bone marrow) within 6 weeks of enrollment
- Acceptable birth control method for men and women
EXCLUSION CRITERIA
- Disease progression within 3 months of last chemotherapy
- Prior myeloablative therapies with bone marrow transplantation or peripheral stem cell rescue
- Platelet count less than 100,000/mm³
- Hypocellular bone marrow (≤ 15% cellularity)
- Marked reduction in bone marrow precursors of one or more cell lines
- History of failed stem cell collection
- Prior treatment with fludarabine
- Prior radioimmunotherapy
- Presence of central nervous system (CNS) lymphoma
- HIV or AIDS-related lymphoma
- Evidence of myelodysplasia on bone marrow biopsy
- Abnormal bone marrow cytogenetics
- Patients who have received prior external beam radiation therapy to more than 25% of active bone marrow
- Patients who have received filgrastim
- Sargramostim therapy within 3 weeks prior to treatment
- Presence of human anti-mouse antibody (HAMA) reactivity in patients with prior exposure to murine antibodies or proteins
- Serious nonmalignant disease or infection, which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives
- Another primary malignancy (other than squamous cell and basal cell cancer of the skin, in situ carcinoma of the cervix, or treated prostate cancer with stable prostate-specific antigen, PSA) for which the patients has not been disease free for at least 3 years
- Major surgery, other than diagnostic surgery within 4 weeks
- Pleural effusion
- Pregnant
- Lactating
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tositumomab + XRT + KI
Arm Description
Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Outcomes
Primary Outcome Measures
Complete Response (CR) Rate
Participants assessed for by the following Complete Response (CR) criteria
CR or Functional CR
No evidence of disease and symptoms
Any macroscopic nodules detected in any organs no longer present.
Any palpable lymph node is normal and greatest diameter is < 1.0 cm.
The enlarged organs decreased in size and not palpable
The bone marrow biopsy and aspirate are negative for disease
Negative for disease by PET-scan (functional CR)
CR Unconfirmed (CRu) criteria
No evidence of disease and symptoms
Any lymph node mass > 1.0 cm^2 diameter has regressed is size by more than 75%.
No macroscopic nodules in any organs
Any palpable lymph node is normal and greatest diameter is < 1.0 cm.
The bone marrow biopsy and aspirate are negative for disease
The bone marrow biopsy may have increased number or size of lymphoid aggregates without cytologic or architectural atypia
Secondary Outcome Measures
Overall Response Rate (ORR)
ORR is assessed as the sum of the overall rates of
CR confirmed by positron emission tomography (PET)
CR not confirmed by PET, and
Partial response (PR) negative for progression by PET
Time-to-Progression (TTP)
Full Information
NCT ID
NCT00490490
First Posted
June 20, 2007
Last Updated
February 9, 2017
Sponsor
Stanford University
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT00490490
Brief Title
Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy
Official Title
Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy for Patients With Relapsed, Bulky Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Low Accrual
Study Start Date
January 2007 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to assess the response rate of patients with relapsed or refractory low-grade or transformed low-grade, CD20-positive, B-cell non-Hodgkin's lymphoma to Iodine-131 (I-131) tositumomab (Bexxar) therapy plus local palliative radiation therapy (XRT).
Detailed Description
Response will be assessed on the basis of the presence or absence of measurable lesion ≥ 1.4 x 1.4 cm (operationally defined as ≥ 2.0 cm2) by radiographic evaluation OR ≥ 1.0 cm in greatest diameter detected by palpation on physical exam
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tositumomab + XRT + KI
Arm Type
Experimental
Arm Description
Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Intervention Type
Drug
Intervention Name(s)
Bexxar (tositumomab)
Other Intervention Name(s)
131-iodine tositumomab
Intervention Description
Tositumomab is a CD20-directed radiotherapeutic (131-iodine) monoclonal antibody indicated for the treatment of patients with CD20-positive, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin's lymphoma who have progressed during or after rituximab therapy, including patients with rituximab-refractory non-Hodgkin's lymphoma. Tositumomab (standard regimen) will be administered at whole body exposure of 75 cGy.
Intervention Type
Procedure
Intervention Name(s)
External beam radiotherapy (XRT)
Other Intervention Name(s)
Radiotherapy (RT)
Intervention Description
Patient-specific XRT will begin within 24 hours of administration of the therapeutic dose of tositumomab. Subjects will receive local XRT to bulky sites of disease measuring at least 5 cm in at least one dimension. The size and number of fields to be treated will determined by the investigators, but will encompass the patient's most symptomatic/threatening site(s) of disease and not cumulatively include more than 25% of the active bone marrow. Subjects will be treated with the 2 x 2 Gy regimen (2 daily fractions of 2 Gy). Sites of disease previously-irradiated with 30 to 40 Gy will not be treated on this study.
Intervention Type
Drug
Intervention Name(s)
Potassium Iodide (KI)
Other Intervention Name(s)
Saturated Solution Potassium Iodide (SSKI), Lugol's solution, Potassium iodide tablets
Intervention Description
Potassium iodide (KI) will be administered as:
Saturated solution potassium iodide (SSKI) 4 drops orally 3-times-a-day,
Lugol's solution 20 drops orally 3-times-a-day, OR
KI tablets 130 mg orally once per day KI treatment will start at least 24 hours prior to tositumomab, and continue daily for 14 days following the last dose of tositumomab
Primary Outcome Measure Information:
Title
Complete Response (CR) Rate
Description
Participants assessed for by the following Complete Response (CR) criteria
CR or Functional CR
No evidence of disease and symptoms
Any macroscopic nodules detected in any organs no longer present.
Any palpable lymph node is normal and greatest diameter is < 1.0 cm.
The enlarged organs decreased in size and not palpable
The bone marrow biopsy and aspirate are negative for disease
Negative for disease by PET-scan (functional CR)
CR Unconfirmed (CRu) criteria
No evidence of disease and symptoms
Any lymph node mass > 1.0 cm^2 diameter has regressed is size by more than 75%.
No macroscopic nodules in any organs
Any palpable lymph node is normal and greatest diameter is < 1.0 cm.
The bone marrow biopsy and aspirate are negative for disease
The bone marrow biopsy may have increased number or size of lymphoid aggregates without cytologic or architectural atypia
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is assessed as the sum of the overall rates of
CR confirmed by positron emission tomography (PET)
CR not confirmed by PET, and
Partial response (PR) negative for progression by PET
Time Frame
12 weeks
Title
Time-to-Progression (TTP)
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA
Histologically confirmed low grade CD20+ B cell non-Hodgkin lymphoma (NHL) patients who have relapsed after chemotherapy or are chemotherapy resistant and have one or more sites of disease measuring more than 5 cm.
The patients must have failed at least one chemotherapy regimen
No anticancer treatment for three weeks prior to study initiation (six weeks if Rituximab, nitrosourea or Mitomycin C)
Fully recovered from all toxicities associated with prior surgery, radiation, chemotherapy or immunotherapy
An institutional review board- (IRB)-approved signed informed consent
Age 19 years or older
Expected survival of at least 6 months
Prestudy Performance Status of 0, 1 or 2 according to the World Health Organization (WHO)
Absolute neutrophil count (ANC) of at least 1,500/mm³
Platelet count at least 100,000/mm³
Hct > 30%
Hgb > 9.0 gm
Bilirubin ≤ 2.0
Creatinine ≤ 2.0
Bone marrow involvement with lymphoma less than 25% (bilateral bone marrow) within 6 weeks of enrollment
Acceptable birth control method for men and women
EXCLUSION CRITERIA
Disease progression within 3 months of last chemotherapy
Prior myeloablative therapies with bone marrow transplantation or peripheral stem cell rescue
Platelet count less than 100,000/mm³
Hypocellular bone marrow (≤ 15% cellularity)
Marked reduction in bone marrow precursors of one or more cell lines
History of failed stem cell collection
Prior treatment with fludarabine
Prior radioimmunotherapy
Presence of central nervous system (CNS) lymphoma
HIV or AIDS-related lymphoma
Evidence of myelodysplasia on bone marrow biopsy
Abnormal bone marrow cytogenetics
Patients who have received prior external beam radiation therapy to more than 25% of active bone marrow
Patients who have received filgrastim
Sargramostim therapy within 3 weeks prior to treatment
Presence of human anti-mouse antibody (HAMA) reactivity in patients with prior exposure to murine antibodies or proteins
Serious nonmalignant disease or infection, which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives
Another primary malignancy (other than squamous cell and basal cell cancer of the skin, in situ carcinoma of the cervix, or treated prostate cancer with stable prostate-specific antigen, PSA) for which the patients has not been disease free for at least 3 years
Major surgery, other than diagnostic surgery within 4 weeks
Pleural effusion
Pregnant
Lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan J Knox
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy
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