Lymphoma, Non-Hodgkin
Conditions
Keywords
rituximab, tositumomab and iodine I 131 tositumomab, non-Hodgkins lymphoma, radioimmunotherapy, anti-B1 antibody, Bexxar, NHL, Tositumomab
Brief summary
Comparison of rituximab versus Iodine I 131 Tositumomab Therapeutic Regimen (Tositumomab and Iodine I 131 Tositumomab or the Bexxar Therapeutic Regimen, formerly called Iodine-131 Anti-B1 Antibody) in subjects with follicular non Hodgkins B cell lymphoma. 506 subjects will be enrolled at 30 to 40 sites in the US, Canada, and Europe. Subjects will be randomly assigned to one of two treatment arms. In Arm A, subjects will receive 375 milligrams/meter2 (mg/m2 )of rituximab, given as an intravenous (IV) infusion once weekly for 4 weeks. In Arm B, subjects will undergo a two-phase treatment. In the first phase, termed the dosimetric dose, subjects will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of 5 millicuries (mCi) (0.18 gigabecquerel \[GBq\]) of Iodine 131 Tositumomab (35 mg). Whole body gamma camera scans will be obtained three times (Day 0; Day 2, 3, or 4; and Day 6 or 7) following the dosimetric dose. The information derived from the scans will enable a patient specific dose to be calculated to deliver the desired total body dose of radiation (65 or 75 centigray \[cGy\]). In the second phase, termed the therapeutic dose, subjects in Arm B will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of the subject specific activity of Iodine 131-conjugated Tositumomab (35 mg). Thyroid blockade will be implemented 24 hours prior to the dosimetric dose and continued for 14 days following the therapeutic dose. Subjects on study will be followed for response and safety at Week 7, Week 13, and every three months for the first and second year, every six months for the third year, and then annually for the forth and fifth years; and then for vital status, additional therapy, and long term safety events through year ten. Follow Up after subsequent NHL therapy will be carried out to assess tolerance of next anti-lymphoma therapy, development of myelodysplasia (MDS)/acute myelogenous leukemia (AML), HAMA or hypothyroidism, unexpected safety issues, and death.
Interventions
BIOLOGICALTositumomab and Iodine I 131 Tositumomab
Dosimetric dose: 450 mg Tositumomab infused over 1 hour followed by 5 mCi I 131 Tositumomab infused over 20 minutes Therapeutic dose: 450 mg Tositumomab infused over 1 hour followed by Individualized mCi activity of I 131 Tositumomab (35 mg) infused over 20 minutes.
BIOLOGICALRituximab
Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of follicular lymphoma * Recurrent lymphoma after one or two qualifying therapy regimen(s) * Patients must not have progressed within 4 weeks of their last chemotherapy dose * Rituximab may have been used once as a single agent, in one continuous course of 4-8 weekly infusions (10-week period), or in combination with chemotherapy in a single prior treatment * Patients whose prior therapy includes rituximab must have had a 6 month or greater response duration following the rituximab-containing regimen. * Performance status of at least 70% on the Karnofsky Scale and an anticipated survival of at least three months * Adequate absolute neutrophil count and platelet count within 21 days of study entry without support of blood products/growth factors * Adequate renal function and adequate hepatic within 21 days of study entry * Measurable disease, with at least one lesion measuring \>/=2.0 cm x 2.0 cm by CT scan * Human Anti Mouse Antigen negative * Written informed consent prior to study entry
Exclusion criteria
* Histologic transformation to diffuse, large cell lymphoma. * History of more than one course of Rituximab * Disease limited to single lymph node or single group of nodes * Involvement of 25% of the intratrabecular marrow by bone marrow biopsy specimen. * Active infection requiring IV antibiotics at the time of study entry * New York Heart Association Class III/IV heart disease * Prior chemotherapy, biologic, radiation or steroid therapy for NHL within 8 weeks * Any prior radioimmunotherapy * Prior history of malignancy other than lymphoma (except for treated basal cell, squamous cell skin cancer, in situ cervical cancer, or other cancer that is disease-free for 5 years) * Known HIV infection * Hepatitis B positive * Known central nervous system involvement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) | From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively) | Event-free survival is defined as the time from the date of randomization to the first occurrence of (whichever came first) progressive disease, death, or additional Non-Hodgkins Lymphoma (NHL) therapy due to disease-related symptoms, threatened end-organ function, cytopenias secondary to NHL, massive bulk disease, or steady progression over at least 6 months. Progressive disease is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm\^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination. |
| Progression-free Survival | From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively) | Progression-free survival is defined as the time from the initial date of dosing to the first documented disease progression or death. Disease assessment was based on the International Workshop to Standardize Response Criteria (IWSRC) for Non-Hodgkin's Lymphoma (NHL). Progression is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm\^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death | From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively) | Time to death is defined as the time from treatment start to the date of death. As a median time to death is not presented for either group, see the outcome measure entitled Number of Participants Who Had Died by the Month Indicated for data regarding time to death. |
| Number of Participants Who Had Died by the Month Indicated | From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively) | The median time to death could not be calculated for participants in either treatment group; thus, data are shown as the number of participants who had died by the month indicated. |
| Time to Next Treatment | Time from study randomization to 120 days after study drug administration | Time to next treatment is defined as time from the date of randomization until the new treatment is needed for NHL. Because too few evaluable participants were enrolled/treated, analysis of the time to next treatment was not conducted as planned. |
| Hematologic Nadir for Absolute Neutrophil Count | Time from study randomization to 120 days after study drug administration | Hematologic toxicity includes the analysis of hematologic nadir, which is defined as the lowest hematology value within 120 days of study drug administration. |
| Hematologic Nadir for Hemoglobin | Time from study randomization to 120 days after study drug administration | Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration. |
| Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count | Time from study randomization to 120 days after study drug administration | Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration. |
| Time to Nadir Values for the Indicated Hematological Parameters | Time from study randomization to 120 days after study drug administration | Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration. Time to nadir is defined as the number of days from the last administration of study drug to nadir. |
| Number of Participants Achieving Response | Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually | Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms (by the IWSRC) if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Confirmation of response was carried out by an independent reviewer |
| Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Time from study randomization to 120 days after study drug administration | Duration of Grade 3/4 toxicity is defined as the time between the date of the first Grade 3/4 lab result to the first lab date with a Grade of 0, 1, or 2 result. Laboratory abnormalities will be recorded as AEs using NCI CTCAE, Version 3, if they are associated with clinical squeal and/or require an intervention. Specific AEs not listed in the NCI criteria will be graded as follows: 1. Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities, 2. Moderate: An event that is sufficiently discomforting to interfere with normal everyday activities, 3. Severe: An event that prevents normal everyday activities, 4. Life-threatening or debilitating, and 5. Death |
| Number of Participants That Developed Hypothyroidism | From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively) | Hypothyroidism is defined as elevated Thyroid-Stimulating Hormone (TSH) or current history of using thyroid medication. The frequency of hypothyroidism at study enrollment will be determined, and participants with hypothyroidism at Baseline were excluded from analysis. |
| Number of Participants With an Infusion Reaction | First 24 hours of study drug administration. | An infusion reaction is defined as any adverse event that occured within 24 hours of an infusion. An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product |
| Number of Hospitalizations | Time of treatment until 90 days post-treatment | The frequency of hospitalizations within 90 days of treatment was summarized. Because too few evaluable participants were enrolled/treated, analysis of the number of hospitalizations was not conducted as planned. |
| Number of Participants With Myelodysplasia/Leukemia | From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively) | The cumulative incidence of myelodysplasia/leukemia was estimated. |
| Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE) | From randomization through Week 26 | 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 it is considered related to the medicinal product. An AE can be 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 SAE is defined as 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/birth defect, or is a Grade 4 (life threatening or disabling) non-hematologic laboratory abnormality assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
| Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Time from study randomization to 120 days after study drug administration | Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration. Time to recovery to Baseline grade is defined as the number of days from the last administration of study drug to a post-nadir hematology value of unmaintained Baseline grade or lower. |
| Duration of Response | Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually | Response duration is defined as the time from the first documented response (complete response, complete response unconfirmed, or partial response) until disease progression. Partial response is defined as at least a 50% decrease in the product of two perpendicular diameters of all measurable lesions; no increase in the size of other nodes, liver, or spleen; and no new disease sites. |
Countries
France, United Kingdom, United States
Participant flow
Pre-assignment details
The study intended to recruit 506 participants to be randomized (1:1) to one of two treatment arms. However, due to feasibility issues, the study was stopped after only 15 participants were enrolled. Of these, 1 participant withdrew prior to receiving the first dose of study treatment; therefore, only 14 comprised the study population.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab 375 mg/m^2 Rituximab 375 milligrams per meters squared (mg/m\^2) given as an intravenous infusion once weekly for four weeks (Day 0, Day 7, Day 14, and Day 21) | 6 |
| TST/I-131 TST Dosimetric dose, Given once on Day 1: Tositumomab (TST) infused over 1 hour, followed by 5 millicuries (mCi) I 131 Tositumomab (I-131 TST) infused over 20 minutes;
Therapeutic dose, Given only once between Day 7 and Day 14:
450 mg TST infused over 1 hour, followed by individualized mCi activity of I-131 TST (35 mg) infused over 20 minutes | 8 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 0 |
Baseline characteristics
| Characteristic | Rituximab 375 mg/m^2 | TST/I-131 TST | Total |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 14.4 | 53.1 years STANDARD_DEVIATION 8 | 53.3 years STANDARD_DEVIATION 11 |
| Gender Female | 3 Participants | 4 Participants | 7 Participants |
| Gender Male | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 6 participants | 8 participants | 14 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 8 / 8 |
| serious Total, serious adverse events | 4 / 6 | 4 / 8 |
Outcome results
Primary
Event-free Survival (EFS)
Event-free survival is defined as the time from the date of randomization to the first occurrence of (whichever came first) progressive disease, death, or additional Non-Hodgkins Lymphoma (NHL) therapy due to disease-related symptoms, threatened end-organ function, cytopenias secondary to NHL, massive bulk disease, or steady progression over at least 6 months. Progressive disease is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm\^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination.
Time frame: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Population: Intent-to-Treat (ITT)-Exposed Population: all participants who received at least one dose of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab 375 mg/m^2 | Event-free Survival (EFS) | 9 Months |
| TST/I-131 TST | Event-free Survival (EFS) | NA Months |
Primary
Progression-free Survival
Progression-free survival is defined as the time from the initial date of dosing to the first documented disease progression or death. Disease assessment was based on the International Workshop to Standardize Response Criteria (IWSRC) for Non-Hodgkin's Lymphoma (NHL). Progression is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm\^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination.
Time frame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Population: ITT-Exposed Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab 375 mg/m^2 | Progression-free Survival | 9 months |
| TST/I-131 TST | Progression-free Survival | NA months |
Secondary
Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters
Duration of Grade 3/4 toxicity is defined as the time between the date of the first Grade 3/4 lab result to the first lab date with a Grade of 0, 1, or 2 result. Laboratory abnormalities will be recorded as AEs using NCI CTCAE, Version 3, if they are associated with clinical squeal and/or require an intervention. Specific AEs not listed in the NCI criteria will be graded as follows: 1. Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities, 2. Moderate: An event that is sufficiently discomforting to interfere with normal everyday activities, 3. Severe: An event that prevents normal everyday activities, 4. Life-threatening or debilitating, and 5. Death
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population. Participants with a Grade 3/4 toxicity level for the indicated hematological parameters were analyzed (reflected by n=X, X). Different participants may have been analyzed for different parameters; thus, the overall number analyzed reflects everyone in the ITT-Exposed Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rituximab 375 mg/m^2 | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Absolute Neutrophil Count (n=0,1) | NA Days |
| Rituximab 375 mg/m^2 | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Hemoglobin (n=0,0) | NA Days |
| Rituximab 375 mg/m^2 | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Platelet Count (n=0,3) | NA Days |
| Rituximab 375 mg/m^2 | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | WBC Count (n=0,4) | NA Days |
| TST/I-131 TST | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | WBC Count (n=0,4) | 22 Days |
| TST/I-131 TST | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Absolute Neutrophil Count (n=0,1) | 910 Days |
| TST/I-131 TST | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Platelet Count (n=0,3) | 22 Days |
| TST/I-131 TST | Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters | Hemoglobin (n=0,0) | NA Days |
Secondary
Duration of Response
Response duration is defined as the time from the first documented response (complete response, complete response unconfirmed, or partial response) until disease progression. Partial response is defined as at least a 50% decrease in the product of two perpendicular diameters of all measurable lesions; no increase in the size of other nodes, liver, or spleen; and no new disease sites.
Time frame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually
Population: ITT-Exposed Population. Only those participants with confirmed or unconfirmed complete response or partial response were analyzed for duration of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab 375 mg/m^2 | Duration of Response | 7.3 months |
| TST/I-131 TST | Duration of Response | NA months |
Secondary
Hematologic Nadir for Absolute Neutrophil Count
Hematologic toxicity includes the analysis of hematologic nadir, which is defined as the lowest hematology value within 120 days of study drug administration.
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population excluding participants that did not have data within the 120 days of study drug administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST/I-131 TST | Hematologic Nadir for Absolute Neutrophil Count | 2.6 10^3/cubic millimeter (mm^3) |
Secondary
Hematologic Nadir for Hemoglobin
Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration.
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab 375 mg/m^2 | Hematologic Nadir for Hemoglobin | 12.3 Grams per deciliter (G/dL) |
| TST/I-131 TST | Hematologic Nadir for Hemoglobin | 11.6 Grams per deciliter (G/dL) |
Secondary
Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count
Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration.
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rituximab 375 mg/m^2 | Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count | Platelets | 161.5 10^3/microliter (µL) |
| Rituximab 375 mg/m^2 | Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count | WBC Count | 4.8 10^3/microliter (µL) |
| TST/I-131 TST | Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count | Platelets | 57.0 10^3/microliter (µL) |
| TST/I-131 TST | Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count | WBC Count | 1.8 10^3/microliter (µL) |
Secondary
Number of Hospitalizations
The frequency of hospitalizations within 90 days of treatment was summarized. Because too few evaluable participants were enrolled/treated, analysis of the number of hospitalizations was not conducted as planned.
Time frame: Time of treatment until 90 days post-treatment
Population: ITT-Exposed Population
Secondary
Number of Participants Achieving Response
Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms (by the IWSRC) if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Confirmation of response was carried out by an independent reviewer
Time frame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 375 mg/m^2 | Number of Participants Achieving Response | Complete response | 1 Participants |
| Rituximab 375 mg/m^2 | Number of Participants Achieving Response | Confirmed complete response | 1 Participants |
| TST/I-131 TST | Number of Participants Achieving Response | Complete response | 6 Participants |
| TST/I-131 TST | Number of Participants Achieving Response | Confirmed complete response | 6 Participants |
Secondary
Number of Participants That Developed Hypothyroidism
Hypothyroidism is defined as elevated Thyroid-Stimulating Hormone (TSH) or current history of using thyroid medication. The frequency of hypothyroidism at study enrollment will be determined, and participants with hypothyroidism at Baseline were excluded from analysis.
Time frame: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab 375 mg/m^2 | Number of Participants That Developed Hypothyroidism | 0 Participants |
| TST/I-131 TST | Number of Participants That Developed Hypothyroidism | 2 Participants |
Secondary
Number of Participants Who Had Died by the Month Indicated
The median time to death could not be calculated for participants in either treatment group; thus, data are shown as the number of participants who had died by the month indicated.
Time frame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 375 mg/m^2 | Number of Participants Who Had Died by the Month Indicated | 6.3 Months | 1 participants |
| Rituximab 375 mg/m^2 | Number of Participants Who Had Died by the Month Indicated | 33.1 Months | 1 participants |
| Rituximab 375 mg/m^2 | Number of Participants Who Had Died by the Month Indicated | 39.6 Months | 1 participants |
| TST/I-131 TST | Number of Participants Who Had Died by the Month Indicated | 6.3 Months | 0 participants |
| TST/I-131 TST | Number of Participants Who Had Died by the Month Indicated | 33.1 Months | 0 participants |
| TST/I-131 TST | Number of Participants Who Had Died by the Month Indicated | 39.6 Months | 0 participants |
Secondary
Number of Participants With an Infusion Reaction
An infusion reaction is defined as any adverse event that occured within 24 hours of an infusion. An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: First 24 hours of study drug administration.
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab 375 mg/m^2 | Number of Participants With an Infusion Reaction | 0 participants |
| TST/I-131 TST | Number of Participants With an Infusion Reaction | 1 participants |
Secondary
Number of Participants With Any Serious Adverse Event (SAE) and Non-serious 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 it is considered related to the medicinal product. An AE can be 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 SAE is defined as 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/birth defect, or is a Grade 4 (life threatening or disabling) non-hematologic laboratory abnormality assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time frame: From randomization through Week 26
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 375 mg/m^2 | Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE) | Non Serious Adverse Evnts | 6 Participants |
| Rituximab 375 mg/m^2 | Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE) | Serious Adverse events | 4 Participants |
| TST/I-131 TST | Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE) | Non Serious Adverse Evnts | 8 Participants |
| TST/I-131 TST | Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE) | Serious Adverse events | 4 Participants |
Secondary
Number of Participants With Myelodysplasia/Leukemia
The cumulative incidence of myelodysplasia/leukemia was estimated.
Time frame: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab 375 mg/m^2 | Number of Participants With Myelodysplasia/Leukemia | 0 Participants |
| TST/I-131 TST | Number of Participants With Myelodysplasia/Leukemia | 0 Participants |
Secondary
Time to Death
Time to death is defined as the time from treatment start to the date of death. As a median time to death is not presented for either group, see the outcome measure entitled Number of Participants Who Had Died by the Month Indicated for data regarding time to death.
Time frame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Population: ITT-Exposed Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab 375 mg/m^2 | Time to Death | NA months |
| TST/I-131 TST | Time to Death | NA months |
Secondary
Time to Nadir Values for the Indicated Hematological Parameters
Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration. Time to nadir is defined as the number of days from the last administration of study drug to nadir.
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab 375 mg/m^2 | Time to Nadir Values for the Indicated Hematological Parameters | Absolute Neutrophil Count (n=0,3) | NA Days | — |
| Rituximab 375 mg/m^2 | Time to Nadir Values for the Indicated Hematological Parameters | Platelet Count (n=6,8) | 33.3 Days | Standard Deviation 18 |
| Rituximab 375 mg/m^2 | Time to Nadir Values for the Indicated Hematological Parameters | WBC Count (n=6,8) | 45.8 Days | Standard Deviation 23.83 |
| Rituximab 375 mg/m^2 | Time to Nadir Values for the Indicated Hematological Parameters | Hemoglobin (n=6,8) | 44.3 Days | Standard Deviation 25.57 |
| TST/I-131 TST | Time to Nadir Values for the Indicated Hematological Parameters | WBC Count (n=6,8) | 41.5 Days | Standard Deviation 4.93 |
| TST/I-131 TST | Time to Nadir Values for the Indicated Hematological Parameters | Absolute Neutrophil Count (n=0,3) | 17.0 Days | Standard Deviation 17.32 |
| TST/I-131 TST | Time to Nadir Values for the Indicated Hematological Parameters | Hemoglobin (n=6,8) | 38.5 Days | Standard Deviation 16.19 |
| TST/I-131 TST | Time to Nadir Values for the Indicated Hematological Parameters | Platelet Count (n=6,8) | 32.6 Days | Standard Deviation 4.21 |
Secondary
Time to Next Treatment
Time to next treatment is defined as time from the date of randomization until the new treatment is needed for NHL. Because too few evaluable participants were enrolled/treated, analysis of the time to next treatment was not conducted as planned.
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population
Secondary
Time to Recovery to Baseline Grade for the Indicated Hematological Parameters
Hematologic nadir is defined as the lowest hematology value within 120 days of study drug administration. Time to recovery to Baseline grade is defined as the number of days from the last administration of study drug to a post-nadir hematology value of unmaintained Baseline grade or lower.
Time frame: Time from study randomization to 120 days after study drug administration
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rituximab 375 mg/m^2 | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Absolute Neutrophil Count (n=0,1) | NA Days |
| Rituximab 375 mg/m^2 | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Hemoglobin (n=6,8) | 46.5 Days |
| Rituximab 375 mg/m^2 | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Platelets Count (n=6,8) | 31.0 Days |
| Rituximab 375 mg/m^2 | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | WBC Count (n=6,8) | 52.0 Days |
| TST/I-131 TST | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | WBC Count (n=6,8) | 73.0 Days |
| TST/I-131 TST | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Absolute Neutrophil Count (n=0,1) | 7 Days |
| TST/I-131 TST | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Platelets Count (n=6,8) | 49.5 Days |
| TST/I-131 TST | Time to Recovery to Baseline Grade for the Indicated Hematological Parameters | Hemoglobin (n=6,8) | 52.0 Days |