Back to resultsRetreatment of Patients With Non-Hodgkin's Lymphoma Who Have Previously Responded to Iodine-131 Anti B1 Antibody
Primary Purpose
Lymphoma, Non-Hodgkin
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tositumomab and Iodine I 131 Tositumomab
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin
Eligibility Criteria
Inclusion Criteria:
- Patients with histologically confirmed initial diagnosis of non-Hodgkin's B-cell lymphoma
- Patients must have previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy
- Patients must have evidence that their tumor tissue had CD20 expression
- Patients must have performance status of at least 60% on the Karnofsky scale and an anticipated survival of at least 3 months
- Patients must have absolute granulocyte count (ANC) greater than 1,500 cells/mm3 and platelet count greater than 100,000 cells/mm3 within 14 days of study entry without support of hematopoietic cytokines or transfusion of blood products
- Patients must have adequate renal (serum creatine less than 1.5 x upper limit of normal) and hepatic function (total bilirubin less than 1.5 x upper limit of normal and hepatic transaminases, AST and ALT, less than 5 x upper limit of normal) within 14 days of study entry
- Patients must have bi-dimensionally measurable disease with a least one lesion greater than or equal to 2 cm x 2 cm by CT scan
- Patients must be at least 18 years of age
- Patients must give written informed consent and sign an Institutional Review Board/Ethics Committee- approved informed consent form prior to study entry
Exclusion Criteria:
- Patients with more than 25% bone marrow involvement
- Patients who have received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or who exhibit persistent clinical evidence of toxicity. The use of systemic steroids much be discontinued at least 1 week prior to study entry.
- Patients with active obstructive hydronephoresis
- Patients with evidence of active infection requiring IV antibiotics at time of study entry
- Patients with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation
- Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
- Patients with known HIV infection
- Patients with known brain or leptomeningeal metasteses
- Patients who are pregnant or nursing
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Retreatment of NHL with Iodine-131 Anti-B1 Antibody
Arm Description
Patients with non-Hodgkin's lymphoma who previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy will undergo two phases of study. In the first phase, patients will receive a dosimetric dose of unlabeled Anti-B1 Antibody (450 mg) followed by Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained after the dosimetric dose and data from three imaging time points will be used to calculate a patient-specific dose to deliver the desired total body dose of radiotherapy. In the second phase, patients will receive the therapeutic dose of unlabeled Anti-B1 Antibody (450 mg) followed by 35 mg of Anti-B1 Antibody labeled with the patient-specific dose to deliver the desired whole body dose of radiation. Patients will be treated with thyroid blocking medication at least 24 hours prior to the first infusion and continuing for 14 days following the last infusion.
Outcomes
Primary Outcome Measures
Number of Participants With Complete Response and Confirmed Complete Response
Complete response (CR) is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Response is defined as the best response achieved at any evaluation. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart.
Duration of Response for All Confirmed Responders (CR + CCR + PR)
For participants with CR, clinical CR (CCR), or partial response (PR), duration of response is defined as the time from the first documented response to the first documented progression. CCR is defined as the complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion <=2 centimeters (cm) in diameter by radiographic evaluation or <=1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations and, if unchanged or if further decreases for 6 months or longer are present, the participant will then be reclassified as a CR (complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease). PR is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.
Progression-free Survival
Progression-free survival (time to progression or death) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the first documented progression or death. Disease Progression (PD) is defined as a >=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be grater than 2 cm diameter by radiographic evaluation or grater than 1 cm diameter by physical examination.
Time to Treatment Failure
Time to treatment failure is defined as the time from the dosimetric dose to the first occurrence of treatment withdrawal, a decision to receive additional therapy, study withdrawal, disease progression, or death.
Overall Survival
Time to death (overall survival) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the date of death from any cause.
Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; or resulted in disability, congenital anomaly, or cancer. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00938041
Brief Title
Retreatment of Patients With Non-Hodgkin's Lymphoma Who Have Previously Responded to Iodine-131 Anti B1 Antibody
Official Title
Retreatment Study of Patients With Non-Hodgkin's Lymphoma Who Have Previously Responded to Iodine-131 Anti B1 Antibody
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
April 1998 (undefined)
Primary Completion Date
May 2003 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
This multicenter study will determine the response rate, the complete response rate, duration of response, time to progression, time-to-treatment failure, safety, and survival following treatment with Iodine-131 Anti-B1 Antibody for the retreatment of patients with non-Hodgkin's lymphoma who previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy. Patients will undergo two phases of study. In the first phase, patients will receive a dosimetric dose of unlabeled Anti-B1 Antibody (450 mg) followed by Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained after the dosimetric dose and data from three imaging time points will be used to calculate a patient-specific dose to deliver the desired total body dose of radiotherapy. In the second phase, patients will receive the therapeutic dose of unlabeled Anti-B1 Antibody (450 mg) followed by 35 mg of Anti-B1 Antibody labeled with the patient-specific dose to deliver the desired whole body dose of radiation. Patients will be treated with thyroid blocking medication at least 24 hours prior to the first infusion and continuing for 14 days following the last infusion.
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
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Retreatment of NHL with Iodine-131 Anti-B1 Antibody
Arm Type
Experimental
Arm Description
Patients with non-Hodgkin's lymphoma who previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy will undergo two phases of study. In the first phase, patients will receive a dosimetric dose of unlabeled Anti-B1 Antibody (450 mg) followed by Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained after the dosimetric dose and data from three imaging time points will be used to calculate a patient-specific dose to deliver the desired total body dose of radiotherapy. In the second phase, patients will receive the therapeutic dose of unlabeled Anti-B1 Antibody (450 mg) followed by 35 mg of Anti-B1 Antibody labeled with the patient-specific dose to deliver the desired whole body dose of radiation. Patients will be treated with thyroid blocking medication at least 24 hours prior to the first infusion and continuing for 14 days following the last infusion.
Intervention Type
Biological
Intervention Name(s)
Tositumomab and Iodine I 131 Tositumomab
Intervention Description
Tositumomab and Iodine I 131 Tositumomab
Primary Outcome Measure Information:
Title
Number of Participants With Complete Response and Confirmed Complete Response
Description
Complete response (CR) is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Response is defined as the best response achieved at any evaluation. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart.
Time Frame
Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Title
Duration of Response for All Confirmed Responders (CR + CCR + PR)
Description
For participants with CR, clinical CR (CCR), or partial response (PR), duration of response is defined as the time from the first documented response to the first documented progression. CCR is defined as the complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion <=2 centimeters (cm) in diameter by radiographic evaluation or <=1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations and, if unchanged or if further decreases for 6 months or longer are present, the participant will then be reclassified as a CR (complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease). PR is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.
Time Frame
Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Title
Progression-free Survival
Description
Progression-free survival (time to progression or death) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the first documented progression or death. Disease Progression (PD) is defined as a >=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be grater than 2 cm diameter by radiographic evaluation or grater than 1 cm diameter by physical examination.
Time Frame
Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Title
Time to Treatment Failure
Description
Time to treatment failure is defined as the time from the dosimetric dose to the first occurrence of treatment withdrawal, a decision to receive additional therapy, study withdrawal, disease progression, or death.
Time Frame
Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Title
Overall Survival
Description
Time to death (overall survival) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the date of death from any cause.
Time Frame
Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Title
Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE)
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; or resulted in disability, congenital anomaly, or cancer. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.
Time Frame
Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with histologically confirmed initial diagnosis of non-Hodgkin's B-cell lymphoma
Patients must have previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy
Patients must have evidence that their tumor tissue had CD20 expression
Patients must have performance status of at least 60% on the Karnofsky scale and an anticipated survival of at least 3 months
Patients must have absolute granulocyte count (ANC) greater than 1,500 cells/mm3 and platelet count greater than 100,000 cells/mm3 within 14 days of study entry without support of hematopoietic cytokines or transfusion of blood products
Patients must have adequate renal (serum creatine less than 1.5 x upper limit of normal) and hepatic function (total bilirubin less than 1.5 x upper limit of normal and hepatic transaminases, AST and ALT, less than 5 x upper limit of normal) within 14 days of study entry
Patients must have bi-dimensionally measurable disease with a least one lesion greater than or equal to 2 cm x 2 cm by CT scan
Patients must be at least 18 years of age
Patients must give written informed consent and sign an Institutional Review Board/Ethics Committee- approved informed consent form prior to study entry
Exclusion Criteria:
Patients with more than 25% bone marrow involvement
Patients who have received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or who exhibit persistent clinical evidence of toxicity. The use of systemic steroids much be discontinued at least 1 week prior to study entry.
Patients with active obstructive hydronephoresis
Patients with evidence of active infection requiring IV antibiotics at time of study entry
Patients with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation
Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
Patients with known HIV infection
Patients with known brain or leptomeningeal metasteses
Patients who are pregnant or nursing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
393229/010
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Retreatment of Patients With Non-Hodgkin's Lymphoma Who Have Previously Responded to Iodine-131 Anti B1 Antibody
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