Back to resultsIodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for Previously Untreated, Advanced-stage, Low Grade Non-Hodgkin's Lymphoma
Primary Purpose
Lymphoma, Non-Hodgkin
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tositumomab and Iodine I 131 Tositumomab (Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody)
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Radioimmunotherapy, Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody, Tositumomab and Iodine I 131 Tositumomab, non-Hodgkin's Lymphoma, Bexxar
Eligibility Criteria
Inclusion Criteria
- Patients must have a histologically confirmed diagnosis of lowgrade non-Hodgkin's B-cell lymphoma. The following low-grade histologies are included: small lymphocytic (with or without plasmacytoid differentiation); follicular, small cleaved; follicular, mixed small cleaved and follicular large cell (less than 50% large cell component); and monocytoid B-cell lymphoma.
- Patients must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti-B1 Antibody (Coulter Clone®) or similar commercially available CD20 antibody (>50% of tumor cells are positive) or evidence of CD20 positivity by flow cytometry (>50% of tumor cells are positive) are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
- Patients must have Ann Arbor stage III or IV extent of disease after complete staging.
- Patients must not have had any previous treatment for low-grade lymphoma including chemotherapy or radiation. They may be newly diagnosed or observed without treatment after diagnosis. Symptomatic and asymptomatic patients will be eligible.
- Patients must have a performance status of at least 60% on the Karnofsky Scale and an anticipated survival of at least 3 months.
- Patients must have an absolute neutrophil count (ANC) >1500 cells/mm3 and a platelet count >100,000 cells/mm3 within 14 days of study entry. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
- Patients must have adequate renal function (defined as serum creatinine <1.5 x upper limit of normal [ULN]) and hepatic function (defined as total bilirubin <1.5 x ULN and aspartate transaminase [AST] <5 x ULN) within 14 days of study entry.
- Patients must have bi-dimensionally measurable disease. At least one lesion must be ≥2 x 2 cm (by computed tomography [CT] scan).
- Patients must be at least 18 years of age.
- Patients must give written informed consent and sign an IRB- approved informed consent form prior to study entry.
Exclusion Criteria
- Patients with more than an average of 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days of study entry. Bilateral posterior iliac crest core biopsies are required if the percentage of intratrabecular space involved exceeds 10% on a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%.
- Patients with evidence of active infection requiring intravenous (IV) antibiotics at the 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 active obstructive hydronephrosis.
- 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 metastases.
- Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test within 7 days of study entry and radiolabeled antibody is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy.
- Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials.
- Patients who were previously given any monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes. This includes engineered chimeric and humanized antibodies.
- Patients who are concurrently receiving either approved or nonapproved (through another protocol) anti-cancer drugs or biologics.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
open-label, single arm
Arm Description
Tositumomab and Iodine I 131 Tositumomab
Outcomes
Primary Outcome Measures
Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
Confirmed response required CR, CCR, or PR, which were confirmed by 2 separate response evaluations >=4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR)
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
Responses were confirmed by two separate response evaluations at least 4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Secondary Outcome Measures
The Estimated Value Represents the Percentage of Participants With a PR
Duration of response (CR, CCR, or PR) is defined as the time from the first documented response to the first documented progression. Progressive Disease (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.
Overall Survival
Overall survival is defined as the time from the treatment start date to the date of death from any cause.
Time to Progression of Disease or Death (Progression-free Survival)
Time to progression is defined as the time from the treatment start date to the first documented progression or death. Progressive Disease 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.
Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study
The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). If the following symptoms (called B-symptoms) are present, a "B" classification is added to the stage: night sweats, intermittant fever, and weight loss. B-symptoms indicate the presence of systemic symptoms. The presence or absence of B-symptoms has prognostic significance and is reflected in the staging of these lymphomas.
Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.
Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.
Progression-free Survival (PFS) Based on Participants' Baseline PCR Status
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent. PFS is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Initial Half-life (t1/2alpha)
t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Terminal Half-life (t1/2beta)
t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours
Area under the concentration-time curve for I-131 tositumomab from time 0 to 120 hours and time 0 to infinity hours (extrapolated) after the end of the dosimetric dose infusion was measured. Unit: %ID*h/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. AUC measures how much drug is in the system over time after infusion.
Clearance Values
Clearance of I-131 tositumomab after intravenous administration was measured. The clearance of a drug measures the rate at which the drug is removed from the body after the dose.
Maximum Concentration (Cmax) Values
Cmax is the maximum observed I-131 tositumomab concentration from time zero (end of the dosimetric dose infusion) to 120 hours after the end of the infusion. Unit: %ID/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. Cmax is the highest drug concentration in the blood after infusion.
Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss)
Volume of distribution at the start of infusion and at steady state of I-131 tositumomab. The volume of distribution measures how much the drug spreads through the body after the dose. Steady state is defined as that state at which the overall intake of a drug is fairly in dynamic equilibrium with its elimination.
Total Body Effective Half-life (EHL)
Total body EHL is the time required for a radioactive element in the body to be diminished by 50% as a result of radioactive decay and biologic elimination. The EHL is equal to the product of the biologic half-life (BHL) and the radioactive half-life (RHL) divided by the sum of the BHL and the RHL: EHL=(BHL * RHL)/(BHL + RHL). BHL is the time it takes for a drug to lose half of its pharmacologic, physiologic, or radiologic activity. RHL is the time taken for half of the radioactive nuclei to decay.
Normal Organ Dosimetry for the Indicated Organs
Organ dosimetry was performed in participants using the kidneys, liver, lungs, spleen, red marrow, urinary bladder, and the remainder of the body as source organs. Organ doses and Iodine I-131 Anti-B1 Antibody biodistribution were comparable across the three Anti-B1 Antibody manufacturers. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). For the spleen (corrected) category, participant-specific corrections were made to account for individual spleen size.
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE)
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. A fatal SAE is a medical event that results in death.
Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA)
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA.
Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment.
Time to HAMA Positivity From the First Dosimetric Dose
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment.
Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.
Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.
Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were categorized to have elevated or normal/low TSH values per the standard TSH ranges of the testing laboratory.
Number of Participants With the Adverse Event (AEs) of Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered to be related to the medical treatment or procedure, that occurs during the course of the study.
Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.
Number of Participants Who Received Thyroid Medication After Treatment
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00996996
Brief Title
Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for Previously Untreated, Advanced-stage, Low Grade Non-Hodgkin's Lymphoma
Official Title
Phase II Trial of Iodine-131 Anti-B1 Antibody for Previously Untreated, Advanced Stage, Low Grade Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
June 1996 (undefined)
Primary Completion Date
March 1999 (Actual)
Study Completion Date
October 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 is a single-arm, single-institution, phase II study of Iodine-131 Anti-B1 Antibody for patients with previously untreated, advanced-stage (stage III or IV) low-grade non-Hodgkin's B-cell lymphoma. A total of 75-80 patients will be enrolled.
Patients will undergo two phases of the study. In the first phase, termed the "dosimetric dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 70 minutes (including a 10-minute flush) immediately followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) which has been trace-labeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained 5 to 8 times between Days 0 and 7 following the dosimetric dose. Using the dosimetric data from 3 imaging timepoints (the imaging timepoints to be used in decreasing order of preference depending on availability of data are Days 0, 3, and 7; Days 0, 4, and 7; Days 0, 3 and 6; Days 0, 4, and 6; Days 0, 2, and 7; and Days 0, 2, and 6), a patient-specific dose of Iodine- 131 to deliver the desired total body dose of radiotherapy will be calculated. In the second phase, termed the "therapeutic dose", patients will receive a 70-minute infusion (including a 10-minute flush) of unlabeled Anti-B1 Antibody (450 mg) immediately followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) labeled with the patient-specific dose of Iodine-131 to deliver a whole body dose of 75 cGy. Patients who are obese will be dosed based upon 137% of their calculated 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 primary endpoint of the study is the determination of the response rate with Iodine-131 Anti-B1 Antibody in previously untreated patients with low-grade non-Hodgkin's lymphoma (NHL). The secondary endpoints include duration of response, safety, radiation dosimetry, and the predictive value of detection of the presence or absence minimal residual disease by molecular techniques on response duration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin
Keywords
Radioimmunotherapy, Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody, Tositumomab and Iodine I 131 Tositumomab, non-Hodgkin's Lymphoma, Bexxar
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
open-label, single arm
Arm Type
Experimental
Arm Description
Tositumomab and Iodine I 131 Tositumomab
Intervention Type
Biological
Intervention Name(s)
Tositumomab and Iodine I 131 Tositumomab (Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody)
Intervention Description
Dosimetric Dose: 450 mg of Anti-B1 Antibody infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by 5 mCi (35 mg) of Iodine-131 Anti-B1 Antibody infused over 30 minutes (inclusive of a 10-minute flush).
Therapeutic Dose: Seven to 14 days after the dosimetric dose, 450 mg of Anti-B1 Antibody infused over 70 minutes (inclusive of a 10-minute flush), immediately followed by the patient-specific milliCurie activity (35 mg) of Iodine-131 Anti-B1 Antibody to deliver a total body dose (TBD) of 75 cGy infused over 30 minutes (inclusive of a 10-minute flush). Obese patients were dosed based upon 137% of their calculated lean body mass.
Primary Outcome Measure Information:
Title
Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
Description
Confirmed response required CR, CCR, or PR, which were confirmed by 2 separate response evaluations >=4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Title
Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR)
Description
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Title
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
Description
Responses were confirmed by two separate response evaluations at least 4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Title
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
Description
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Secondary Outcome Measure Information:
Title
The Estimated Value Represents the Percentage of Participants With a PR
Description
Duration of response (CR, CCR, or PR) is defined as the time from the first documented response to the first documented progression. Progressive Disease (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.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Title
Overall Survival
Description
Overall survival is defined as the time from the treatment start date to the date of death from any cause.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Title
Time to Progression of Disease or Death (Progression-free Survival)
Description
Time to progression is defined as the time from the treatment start date to the first documented progression or death. Progressive Disease 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.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Title
Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study
Description
The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). If the following symptoms (called B-symptoms) are present, a "B" classification is added to the stage: night sweats, intermittant fever, and weight loss. B-symptoms indicate the presence of systemic symptoms. The presence or absence of B-symptoms has prognostic significance and is reflected in the staging of these lymphomas.
Time Frame
Baseline and up to 12 years (long-term follow up)
Title
Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment
Description
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.
Time Frame
Baseline and up to 12 years (long-term follow up)
Title
Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment
Description
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.
Time Frame
Baseline and up to 12 years (long-term follow up)
Title
Progression-free Survival (PFS) Based on Participants' Baseline PCR Status
Description
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent. PFS is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Time Frame
Baseline and up to 12 years (long-term follow up)
Title
Initial Half-life (t1/2alpha)
Description
t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Terminal Half-life (t1/2beta)
Description
t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours
Description
Area under the concentration-time curve for I-131 tositumomab from time 0 to 120 hours and time 0 to infinity hours (extrapolated) after the end of the dosimetric dose infusion was measured. Unit: %ID*h/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. AUC measures how much drug is in the system over time after infusion.
Time Frame
0-120 hours and 0-infinity hours from the dosimetric dose (given only on Day 0) and 0-120 hours and 0-infinity hours from the therapeutic dose (given only on Day 7)
Title
Clearance Values
Description
Clearance of I-131 tositumomab after intravenous administration was measured. The clearance of a drug measures the rate at which the drug is removed from the body after the dose.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Maximum Concentration (Cmax) Values
Description
Cmax is the maximum observed I-131 tositumomab concentration from time zero (end of the dosimetric dose infusion) to 120 hours after the end of the infusion. Unit: %ID/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. Cmax is the highest drug concentration in the blood after infusion.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss)
Description
Volume of distribution at the start of infusion and at steady state of I-131 tositumomab. The volume of distribution measures how much the drug spreads through the body after the dose. Steady state is defined as that state at which the overall intake of a drug is fairly in dynamic equilibrium with its elimination.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Total Body Effective Half-life (EHL)
Description
Total body EHL is the time required for a radioactive element in the body to be diminished by 50% as a result of radioactive decay and biologic elimination. The EHL is equal to the product of the biologic half-life (BHL) and the radioactive half-life (RHL) divided by the sum of the BHL and the RHL: EHL=(BHL * RHL)/(BHL + RHL). BHL is the time it takes for a drug to lose half of its pharmacologic, physiologic, or radiologic activity. RHL is the time taken for half of the radioactive nuclei to decay.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Normal Organ Dosimetry for the Indicated Organs
Description
Organ dosimetry was performed in participants using the kidneys, liver, lungs, spleen, red marrow, urinary bladder, and the remainder of the body as source organs. Organ doses and Iodine I-131 Anti-B1 Antibody biodistribution were comparable across the three Anti-B1 Antibody manufacturers. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). For the spleen (corrected) category, participant-specific corrections were made to account for individual spleen size.
Time Frame
0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Title
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE)
Description
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. A fatal SAE is a medical event that results in death.
Time Frame
From Baseline up to 12 years from the start of treatment (long-term follow up)
Title
Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA)
Description
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA.
Time Frame
From Baseline up to 2 years from the start of treatment
Title
Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline
Description
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment.
Time Frame
From Baseline up to 2 years from the start of treatment
Title
Time to HAMA Positivity From the First Dosimetric Dose
Description
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment.
Time Frame
From Baseline up to 2 years from the start of treatment
Title
Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline
Description
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.
Time Frame
Baseline
Title
Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated
Description
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.
Time Frame
Baseline and up to 12 years (long-term follow up)
Title
Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline
Description
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were categorized to have elevated or normal/low TSH values per the standard TSH ranges of the testing laboratory.
Time Frame
Baseline and up to 12 years from the start of treatment
Title
Number of Participants With the Adverse Event (AEs) of Hypothyroidism
Description
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered to be related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame
Baseline and up to 12 years from the start of treatment
Title
Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism
Description
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.
Time Frame
Baseline and up to 12 years from the start of treatment
Title
Number of Participants Who Received Thyroid Medication After Treatment
Description
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.
Time Frame
From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients must have a histologically confirmed diagnosis of lowgrade non-Hodgkin's B-cell lymphoma. The following low-grade histologies are included: small lymphocytic (with or without plasmacytoid differentiation); follicular, small cleaved; follicular, mixed small cleaved and follicular large cell (less than 50% large cell component); and monocytoid B-cell lymphoma.
Patients must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti-B1 Antibody (Coulter Clone®) or similar commercially available CD20 antibody (>50% of tumor cells are positive) or evidence of CD20 positivity by flow cytometry (>50% of tumor cells are positive) are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
Patients must have Ann Arbor stage III or IV extent of disease after complete staging.
Patients must not have had any previous treatment for low-grade lymphoma including chemotherapy or radiation. They may be newly diagnosed or observed without treatment after diagnosis. Symptomatic and asymptomatic patients will be eligible.
Patients must have a performance status of at least 60% on the Karnofsky Scale and an anticipated survival of at least 3 months.
Patients must have an absolute neutrophil count (ANC) >1500 cells/mm3 and a platelet count >100,000 cells/mm3 within 14 days of study entry. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
Patients must have adequate renal function (defined as serum creatinine <1.5 x upper limit of normal [ULN]) and hepatic function (defined as total bilirubin <1.5 x ULN and aspartate transaminase [AST] <5 x ULN) within 14 days of study entry.
Patients must have bi-dimensionally measurable disease. At least one lesion must be ≥2 x 2 cm (by computed tomography [CT] scan).
Patients must be at least 18 years of age.
Patients must give written informed consent and sign an IRB- approved informed consent form prior to study entry.
Exclusion Criteria
Patients with more than an average of 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days of study entry. Bilateral posterior iliac crest core biopsies are required if the percentage of intratrabecular space involved exceeds 10% on a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%.
Patients with evidence of active infection requiring intravenous (IV) antibiotics at the 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 active obstructive hydronephrosis.
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 metastases.
Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test within 7 days of study entry and radiolabeled antibody is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy.
Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials.
Patients who were previously given any monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes. This includes engineered chimeric and humanized antibodies.
Patients who are concurrently receiving either approved or nonapproved (through another protocol) anti-cancer drugs or biologics.
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
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104517
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
104517
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
104517
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
104517
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
104517
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
104517
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
104517
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for Previously Untreated, Advanced-stage, Low Grade Non-Hodgkin's Lymphoma
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