Back to resultsTositumomab And Iodine I 131-Tositumomab In Patients With Relapsed Indolent Non-Hodgkin's Lymphoma
Primary Purpose
Lymphoma, Non-Hodgkin
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Tositumomab 450 mg
Tositumomab 35 mg
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring BEXXAR, non-Hodgkin's Lymphoma, tositumomab, I-131
Eligibility Criteria
Inclusion criteria: Patients must have evidence of persistent or progressive follicular grade, 1, 2 or 3 or marginal zone B-cell non-Hodgkin's lymphoma. Must have received at least two prior courses of systemic treatment including at least one treatment of rituximab (lymphoma must not have progressed during their most recent systemic chemotherapy treatment). Must have evidence that their lymphoma expresses CD20 antigen and have adequate renal and hepatic function. Exclusion criteria: Received chemotherapy, radiation therapy, immunosuppressants or cytokine treatment within 4 weeks prior to study entry. Have active obstructive hydronephrosis. Had prior autologous hematopoietic stem cell transplant or any allogenic stem cell transplant. Have active infection requiring IV antibiotics. Have brain or leptomeningeal metastasis. Had previous allergic reaction to iodine, previously received radioimmunotherapy or are currently receiving approved or experimental anti-cancer drugs. Patients who are pregnant or breast feeding, have known HIV infection, or are Human anti-murine antibody (HAMA) positive. Other criteria will be evaluated at the screening visit.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1
Arm Description
Participants underwent two phases of treatment: an initial DD, followed by a therapeutic dose. The one-day DD comprised a 1 hr IV infusion of 450 mg unlabeled TST, followed by a 20 min IV infusion of 35 mg TST labeled with 185 MBq (5.0 mCi) of I 131. After 7 to 14 days, the one-day therapeutic dose comprised a second 1 hr IV infusion of 450 mg unlabeled TST, followed by a 20 min IV infusion of 35 mg TST labeled with I 131 with an administered activity (MBq or mCi) determined from the dosimetry calculation.
Outcomes
Primary Outcome Measures
Response Rate
Responders are defined as participants with Complete Response (CR: disappearance of all clinical and radiological evidence of lymphoma), Clinical Complete Response (CCR: all criteria met for CR, except there is a residual nodal mass >15 millimeters), or Partial Response (PR: 50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Response is based on objective evaluation, using the guidelines developed by The International Workshop to Standardize Response Criteria, independent of the investigator's evaluation.
Secondary Outcome Measures
Complete response rate (CR)
Investigator-assessed confirmed CR is defined as the disappearance of all clinical and radiological evidence of lymphoma. Response is based on objective evaluation, using the guidelines developed by The International Workshop to Standardize Response Criteria, independent of the investigator's evaluation.
Duration of response
Duration of response is defined as the time from the first documented response to the first documented disease progression. Response is based on objective evaluation, using the guidelines developed by The International Workshop to Standardize Response Criteria, independent of the investigator's evaluation. Disease progression is defined as a 50% increase in the sum of the products of the two perpendicular diameters of all measurable lesions, or the appearance of new lesions.
Progression-free survival (PFS)
PFS is defined as the time interval between the date of the DD to the first date at which progressive disease (PD) or death is observed. PD is defined as a 50% increase in the sum of the products of two perpendicular diameters of all measurable lesions, or the appearance of new lesions. Participants with no evidence of PD were censored to the last date of contact; and those who died for any reason in the absense of PD were classified as having experienced PD on the date of death. For non-responders, duration of PFS was recorded as 0. Participants were censored if they withdrew without PD.
Adverse events
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly in a child from a parent who was exposed to treatment; or is an SAE based on medical or scientific judgement of the investigator.
Quality of Life
Qualty of Life will be asessed utilizing several scales and questionnaires: FACT-G questionnaire was designed to measure multidimensional quality of life (QOL) in participants with cancer. FACT-LymThe FACT-Lym subscale questionnaire is a cancer-specific questionnaire designed to measure multidimensional QOL in participants with lymphoma.
Resource Utilization Assessment
The Resource Utilization Assessment questionnaires are used to assess the resource utilization of the participant and impacted associates (e.g., family members, caregivers) as well as costs involved to treat participants receiving TST and I 131 TST. As an assessment of general health, participants were asked to rate their activity level on average in the last 7 days on an 11-point scale: 0= exhausted in bed all day; 10=normal activity level.
Duration of Overall Survival
Survival time is defined as the number of weeks from the first study medication administration to the date of death. In the absence of confirmation of death, survival time was censored to the last date the participant was known be alive. If the participant was alive at the time of analysis, then the survival time was censored at the date of last contact.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00240565
Brief Title
Tositumomab And Iodine I 131-Tositumomab In Patients With Relapsed Indolent Non-Hodgkin's Lymphoma
Official Title
A Single Arm, Open-label, Multicentre, Phase II Study of Tositumomab and Iodine 131-Tositumomab in Subjects With Indolent Non-Hodgkin's Lymphoma Who Have Previously Received Rituximab.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will further characterize the activity of Tositumomab and Iodine I 131-Tositumomab in patients with relapsed indolent non-Hodgkin's Lymphoma who have progressed following treatment with rituximab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin
Keywords
BEXXAR, non-Hodgkin's Lymphoma, tositumomab, I-131
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
93 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Participants underwent two phases of treatment: an initial DD, followed by a therapeutic dose. The one-day DD comprised a 1 hr IV infusion of 450 mg unlabeled TST, followed by a 20 min IV infusion of 35 mg TST labeled with 185 MBq (5.0 mCi) of I 131. After 7 to 14 days, the one-day therapeutic dose comprised a second 1 hr IV infusion of 450 mg unlabeled TST, followed by a 20 min IV infusion of 35 mg TST labeled with I 131 with an administered activity (MBq or mCi) determined from the dosimetry calculation.
Intervention Type
Drug
Intervention Name(s)
Tositumomab 450 mg
Intervention Description
Unlabeled TST
Intervention Type
Drug
Intervention Name(s)
Tositumomab 35 mg
Intervention Description
TST labeled with 185 megaBecqueral (mbq) of iodine 131
Primary Outcome Measure Information:
Title
Response Rate
Description
Responders are defined as participants with Complete Response (CR: disappearance of all clinical and radiological evidence of lymphoma), Clinical Complete Response (CCR: all criteria met for CR, except there is a residual nodal mass >15 millimeters), or Partial Response (PR: 50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Response is based on objective evaluation, using the guidelines developed by The International Workshop to Standardize Response Criteria, independent of the investigator's evaluation.
Time Frame
Week 26
Secondary Outcome Measure Information:
Title
Complete response rate (CR)
Description
Investigator-assessed confirmed CR is defined as the disappearance of all clinical and radiological evidence of lymphoma. Response is based on objective evaluation, using the guidelines developed by The International Workshop to Standardize Response Criteria, independent of the investigator's evaluation.
Time Frame
From the start of treatment (Study Day 0, Baseline) until long-term follow-up (every 6 months until 5 years from the time of study entry)
Title
Duration of response
Description
Duration of response is defined as the time from the first documented response to the first documented disease progression. Response is based on objective evaluation, using the guidelines developed by The International Workshop to Standardize Response Criteria, independent of the investigator's evaluation. Disease progression is defined as a 50% increase in the sum of the products of the two perpendicular diameters of all measurable lesions, or the appearance of new lesions.
Time Frame
5 years
Title
Progression-free survival (PFS)
Description
PFS is defined as the time interval between the date of the DD to the first date at which progressive disease (PD) or death is observed. PD is defined as a 50% increase in the sum of the products of two perpendicular diameters of all measurable lesions, or the appearance of new lesions. Participants with no evidence of PD were censored to the last date of contact; and those who died for any reason in the absense of PD were classified as having experienced PD on the date of death. For non-responders, duration of PFS was recorded as 0. Participants were censored if they withdrew without PD.
Time Frame
5 years or until death
Title
Adverse events
Description
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly in a child from a parent who was exposed to treatment; or is an SAE based on medical or scientific judgement of the investigator.
Time Frame
5 years or until death
Title
Quality of Life
Description
Qualty of Life will be asessed utilizing several scales and questionnaires: FACT-G questionnaire was designed to measure multidimensional quality of life (QOL) in participants with cancer. FACT-LymThe FACT-Lym subscale questionnaire is a cancer-specific questionnaire designed to measure multidimensional QOL in participants with lymphoma.
Time Frame
5 Years
Title
Resource Utilization Assessment
Description
The Resource Utilization Assessment questionnaires are used to assess the resource utilization of the participant and impacted associates (e.g., family members, caregivers) as well as costs involved to treat participants receiving TST and I 131 TST. As an assessment of general health, participants were asked to rate their activity level on average in the last 7 days on an 11-point scale: 0= exhausted in bed all day; 10=normal activity level.
Time Frame
Week 26
Title
Duration of Overall Survival
Description
Survival time is defined as the number of weeks from the first study medication administration to the date of death. In the absence of confirmation of death, survival time was censored to the last date the participant was known be alive. If the participant was alive at the time of analysis, then the survival time was censored at the date of last contact.
Time Frame
5 years or until death
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patients must have evidence of persistent or progressive follicular grade, 1, 2 or 3 or marginal zone B-cell non-Hodgkin's lymphoma.
Must have received at least two prior courses of systemic treatment including at least one treatment of rituximab (lymphoma must not have progressed during their most recent systemic chemotherapy treatment).
Must have evidence that their lymphoma expresses CD20 antigen and have adequate renal and hepatic function.
Exclusion criteria:
Received chemotherapy, radiation therapy, immunosuppressants or cytokine treatment within 4 weeks prior to study entry.
Have active obstructive hydronephrosis.
Had prior autologous hematopoietic stem cell transplant or any allogenic stem cell transplant.
Have active infection requiring IV antibiotics.
Have brain or leptomeningeal metastasis.
Had previous allergic reaction to iodine, previously received radioimmunotherapy or are currently receiving approved or experimental anti-cancer drugs.
Patients who are pregnant or breast feeding, have known HIV infection, or are Human anti-murine antibody (HAMA) positive.
Other criteria will be evaluated at the screening visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
GSK Investigational Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
GSK Investigational Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
GSK Investigational Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
GSK Investigational Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4J 1C5
Country
Canada
Facility Name
GSK Investigational Site
City
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
GSK Investigational Site
City
Quebec
ZIP/Postal Code
G1S 4L8
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
24528219
Citation
Olney HJ, Freeman MA, Stewart DA, Mangel JE, White DJ, Elia-Pacitti JO. Prolonged progression-free survival and preserved quality of life in the Canadian prospective study of tositumomab and iodine(131)-tositumomab for previously treated, rituximab-exposed, indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2014 Dec;55(12):2754-60. doi: 10.3109/10428194.2014.894190. Epub 2014 Apr 3.
Results Reference
derived
Learn more about this trial
Tositumomab And Iodine I 131-Tositumomab In Patients With Relapsed Indolent Non-Hodgkin's Lymphoma
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