Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab
- Conditions
- Lymphoma, Non-Hodgkin
- Interventions
- Biological: Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab)
- Registration Number
- NCT00996593
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a single-arm, open-label, multicenter study of Iodine I-131 Anti B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for treatment of non-Hodgkin's lymphoma (NHL) who were previously treated with rituximab antibody. Patients must have been treated with at least 4 doses of rituximab and have progressed during or following rituximab therapy.
Patients will undergo two dosing phases of study. In the first phase, termed the "dosimetric dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 70 minutes immediately followed by a 30-minute infusion of Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4; and Day 6 or 7 following the dosimetric dose. Using the dosimetric data from three imaging timepoints, a patient-specific dose of Iodine-131 will be calculated to deliver the desired total body dose of radiotherapy. In the second phase, termed the "therapeutic dose", patients will receive a 70-minute infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by a 30-minute infusion of 35 mg Anti-B1 Antibody labeled with a patient-specific dose of Iodine-131 to deliver a whole body dose of 75 cGy to patients with no hematologic risk factors. Patients who have platelet counts of 100,001-149,999 cells/mm3 will receive 65 cGy and patients who are obese will be dosed based upon 137% of their lean body mass. Patients will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion of the Iodine-131 Anti-B1 Antibody (i.e., dosimetric dose) and continuing for 14 days following the last infusion of Iodine-131 Anti-B1 Antibody (i.e., therapeutic dose).
The endpoints of the study are to determine the response rate, complete response rate, duration of response, and time to progression or death, based on both a Masked Independent Randomized Radiographic and Oncologic Review (MIRROR) panel and the Investigators, and the Investigators' assessment of safety and survival of survival of Iodine-131 Anti-B1 Antibody therapy in NHL patients who have previously been treated with rituximab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description open-label, single arm Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) -
- Primary Outcome Measures
Name Time Method Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years 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.
Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years CCR is defined as the complete resolution of all disease-related symptoms; 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. If the extent of disease was unchanged or if further decreases occurred for 6 months or longer, the participant was reclassified as having a CR.
Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Confirmed PR is defined as a \>=50 percent reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.
Duration of Response for All Confirmed Responders (CR, CCR, or PR) as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Response duration is defined as the time from the first documented response until disease progression.
Duration of Response for CR and CCR as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Response duration is defined as the time from the first documented response until disease progression.
Duration of Response for All Confirmed Partial Responders as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Response duration is defined as the time from the first documented response until progressive disease.
Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Responders in This Study Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Response corresponds to the best response evaluation (ordered by CR, CCR, and PR) and does not require subsequent confirmation. Participants with CR, CCR, or PR are considered to be responders. A prior response to rituximab refers to a CR, CCR, or PR after rituximab treatment before enrollment into Study BEX104507.
Duration of Response for Confirmed CR as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Response duration is defined as the time from the first documented response until disease progression. Disease progression is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measureable lesions or the appearance of any new lesion. Individual lesions must be \>2 centimeters (cm) in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Duration of Response for All Participants Classified as Responders With or Without a Prior Response to Rituximab Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Duration of response is defined as the time from the first documented response to disease progression.
Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Having a Complete Response (CR) in This Study Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years 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.
Duration of Response for All Participants With CR With or Without a Prior Response to Rituximab Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Duration of response is defined as the time from the first documented response to disease progression.
Progression-free Survival for Participants With or Without a Prior Response to Rituximab Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Progression-free survival is defined as the time from treatment start to the first documented occurrence of disease progression or death.
Time to Progression of Disease or Death in All Responders, Participants With CR + CCR, and Participants With PR as Assessed by the Investigator Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Overall Survival Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Overall survival is defined as the time from the treatment start date to the date of death from any cause.
- Secondary Outcome Measures
Name Time Method Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the adverse event was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities were assumed to be possibly or probably related to study drug.
Number of Participants With the Indicated Type of Infection Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has the infection under investigation, in which case therapeutic treatment with anti-infective is required.
Number of Participants With an Infection for Which Anti-infectives Were Administered Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the investigator's medical judgement.
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Nadir is defined as the lowest laboratory value recorded following the administration of the study medication. Time to recovery to baseline in hematologic laboratory evaluations is the time required for recovery from nadir values to baseline values.
Nadir Values for ANC, a Hematologic Parameter Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights against infection.
Nadir Values for Hemoglobin, a Hematologic Parameter Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells.
Nadir Values for Hematologic Parameters Platelets and WBC Count Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells.
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.
Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.