Lymphoma, Non-Hodgkin
Conditions
Brief summary
This multicenter study will determine the response rate, the complete response rate, duration of response, time to progression, time-to-treatment failure, safety, and survival following treatment with Iodine-131 Anti-B1 Antibody for the retreatment of patients with non-Hodgkin's lymphoma who previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy. Patients will undergo two phases of study. In the first phase, patients will receive a dosimetric dose of unlabeled Anti-B1 Antibody (450 mg) followed by Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained after the dosimetric dose and data from three imaging time points will be used to calculate a patient-specific dose to deliver the desired total body dose of radiotherapy. In the second phase, patients will receive the therapeutic dose of unlabeled Anti-B1 Antibody (450 mg) followed by 35 mg of Anti-B1 Antibody labeled with the patient-specific dose to deliver the desired whole body dose of radiation. Patients will be treated with thyroid blocking medication at least 24 hours prior to the first infusion and continuing for 14 days following the last infusion.
Interventions
BIOLOGICALTositumomab and Iodine I 131 Tositumomab
Tositumomab and Iodine I 131 Tositumomab
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically confirmed initial diagnosis of non-Hodgkin's B-cell lymphoma * Patients must have previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy * Patients must have evidence that their tumor tissue had CD20 expression * Patients must have performance status of at least 60% on the Karnofsky scale and an anticipated survival of at least 3 months * Patients must have absolute granulocyte count (ANC) greater than 1,500 cells/mm3 and platelet count greater than 100,000 cells/mm3 within 14 days of study entry without support of hematopoietic cytokines or transfusion of blood products * Patients must have adequate renal (serum creatine less than 1.5 x upper limit of normal) and hepatic function (total bilirubin less than 1.5 x upper limit of normal and hepatic transaminases, AST and ALT, less than 5 x upper limit of normal) within 14 days of study entry * Patients must have bi-dimensionally measurable disease with a least one lesion greater than or equal to 2 cm x 2 cm by CT scan * Patients must be at least 18 years of age * Patients must give written informed consent and sign an Institutional Review Board/Ethics Committee- approved informed consent form prior to study entry
Exclusion criteria
* Patients with more than 25% bone marrow involvement * Patients who have received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or who exhibit persistent clinical evidence of toxicity. The use of systemic steroids much be discontinued at least 1 week prior to study entry. * Patients with active obstructive hydronephoresis * Patients with evidence of active infection requiring IV antibiotics at time of study entry * Patients with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation * Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years * Patients with known HIV infection * Patients with known brain or leptomeningeal metasteses * Patients who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response and Confirmed Complete Response | Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months) | Complete response (CR) is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Response is defined as the best response achieved at any evaluation. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. |
| Duration of Response for All Confirmed Responders (CR + CCR + PR) | Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months) | For participants with CR, clinical CR (CCR), or partial response (PR), duration of response is defined as the time from the first documented response to the first documented progression. CCR is defined as the complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion \<=2 centimeters (cm) in diameter by radiographic evaluation or \<=1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations and, if unchanged or if further decreases for 6 months or longer are present, the participant will then be reclassified as a CR (complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease). PR is defined as a \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions. |
| Progression-free Survival | Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months) | Progression-free survival (time to progression or death) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the first documented progression or death. Disease Progression (PD) is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be grater than 2 cm diameter by radiographic evaluation or grater than 1 cm diameter by physical examination. |
| Time to Treatment Failure | Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months) | Time to treatment failure is defined as the time from the dosimetric dose to the first occurrence of treatment withdrawal, a decision to receive additional therapy, study withdrawal, disease progression, or death. |
| Overall Survival | Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months) | Time to death (overall survival) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the date of death from any cause. |
| Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE) | Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; or resulted in disability, congenital anomaly, or cancer. Refer to the general AE/SAE module for a complete list of all AEs and SAEs. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab Participants were treated with a saturated solution of potassium iodide (KI), Lugol's solution, or KI tablets orally starting at least 24 hours prior to the first infusion of Iodine I-131 Tositumomab (TST) and continuing for 14 days following the last infusion of Iodine I-131 TST. Participants received treatment in two phases. The dosimetric dose was administered in Phase 1 as 450 milligrams (mg) of TST infused over 1 hour, followed by 35 mg of antibody containing 5 millicurie (mCi) of Iodine I-131 TST infused over 20 minutes (min), followed by a 10-min normal saline flush. The therapeutic dose, administered 7-14 days after the dosimetric dose, was administered as 450 mg of TST infused over 1 hour, followed by 35 mg of antibody radiolabeled with enough Iodine I-131 TST to deliver 75 centigrey (cGy) infused over 20 min, followed by a 10-min normal saline flush. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adrenal Insufficiency | 3 |
| Overall Study | Death | 12 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Progressive Disease | 5 |
| Overall Study | Received Alternative Therapy | 1 |
Baseline characteristics
| Characteristic | Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab |
|---|---|
| Age, Continuous | 58.1 Years STANDARD_DEVIATION 12.5 |
| Gender Female | 13 Participants |
| Gender Male | 19 Participants |
| Race/Ethnicity, Customized White | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 32 |
| serious Total, serious adverse events | 18 / 32 |
Outcome results
Primary
Duration of Response for All Confirmed Responders (CR + CCR + PR)
For participants with CR, clinical CR (CCR), or partial response (PR), duration of response is defined as the time from the first documented response to the first documented progression. CCR is defined as the complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion \<=2 centimeters (cm) in diameter by radiographic evaluation or \<=1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations and, if unchanged or if further decreases for 6 months or longer are present, the participant will then be reclassified as a CR (complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease). PR is defined as a \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.
Time frame: Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Population: ITT-Exposed Population. Only those participants with a confirmed CR, CCR, or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Duration of Response for All Confirmed Responders (CR + CCR + PR) | 18.9 Months |
Primary
Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; or resulted in disability, congenital anomaly, or cancer. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.
Time frame: Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE) | Any Adverse Event | 32 Participants |
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE) | Any Serious Adverse Event | 18 Participants |
Primary
Number of Participants With Complete Response and Confirmed Complete Response
Complete response (CR) is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Response is defined as the best response achieved at any evaluation. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart.
Time frame: Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Population: ITT-Exposed Population: all participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Number of Participants With Complete Response and Confirmed Complete Response | Complete response | 8 Participants |
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Number of Participants With Complete Response and Confirmed Complete Response | Confirmed complete response | 8 Participants |
95% CI: [10, 40]
95% CI: [10, 40]
Primary
Overall Survival
Time to death (overall survival) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the date of death from any cause.
Time frame: Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Population: ITT-Exposed Population. Participants who did not die were censored at the date of their last contact in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Overall Survival | 64.2 Months |
Primary
Progression-free Survival
Progression-free survival (time to progression or death) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the first documented progression or death. Disease Progression (PD) is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be grater than 2 cm diameter by radiographic evaluation or grater than 1 cm diameter by physical examination.
Time frame: Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Population: ITT-Exposed Population. Participants who did not progress or die were censored at their date of last contact in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Progression-free Survival | 11.9 Months |
Primary
Time to Treatment Failure
Time to treatment failure is defined as the time from the dosimetric dose to the first occurrence of treatment withdrawal, a decision to receive additional therapy, study withdrawal, disease progression, or death.
Time frame: Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Population: ITT-Exposed Population. Participants who withdrew from the study for reasons other than progression or death were censored at the date of study withdrawal. Participants who did not meet any of the criteria for treatment failure were censored at their date of last contact in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Antibody Radiolabeled Iodine I-131 Tositumomab | Time to Treatment Failure | 11.7 Months |