Lymphoma, Non-Hodgkin
Conditions
Brief summary
This is a single-arm, single institution, phase II study of fludarabine monophosphate followed by Iodine I 131 Tositumomab for patients with previously untreated, advanced-stage (stage III or IV) low-grade, transformed low-grade and follicular non-Hodgkin's lymphoma. The primary objective of the study will be to evaluate the safety of this treatment combination and the secondary endpoint will be to evaluate efficacy.
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 must be age 18 years or older. * Patients must have a histologically-confirmed diagnosis of low-grade or follicular non-Hodgkin's B-cell lymphoma. * Patients must have Ann Arbor stage III or IV extent of disease after completing staging. * Patients must have bi-dimensionally measurable disease. At least one lesion must have both perpendicular diameters \> 2 cm. * Patients must have evidence that their tumor expresses the CD20 antigen by immunohistochemistry or flow cytometry. * Patients must have no previous treatment for NHL. * Patients must have a Karnofsky performance status of at least 60% and an anticipated survival of at least 3 months. * Patients must have absolute granulocyte count greater than or equal to 1500 cells/mm3 and a platelet count \> 100,000 cells/mm3 within 14 days of study entry and not require sustained support with hematopoietic cytokines or transfusion of blood products. * Patients must have adequate renal and hepatic function. * Patients must sign IRB approved informed consent form(s) prior to study entry.
Exclusion criteria
* Patients who received systemic steroids within 1 week of study entry, except patients on maintenance steroid therapy for a non-cancerous disease. * Patients with evidence of active infection requiring intravenous 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 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 at screening and on the day fludarabine treatment is started. Treatment 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 iodine I 131 tositumomab therapy. * 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 hypersensitivity to fludarabine. * Patients who are receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics. * Patients who are HAMA positive. * Patients with previous allergic reaction to iodine. This does not include reacting to intravenous iodine containing contrast materials. Inclusion Criteria for Iodine I 131 Tositumomab Therapy * Patients who completed 3 cycles of fludarabine. * Patients must have absolute granulocyte count ≥ to 1500/mm3, platelet count of ≥ 100,000/mm3 (≥ 150,000/mm3 if \> 25% bone marrow involvement at restaging), and not require sustained support with hematopoietic cytokines or transfusions with blood products. * Patients must have adequate renal and hepatic function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease. Supportive care involved administration of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), red blood cell (RBC) transfusions, erythropoietin, and platelet transfusions. |
| Nadir Values for Hemoglobin | up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose) | Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose). |
| Nadir Values for Platelet Count | up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose) | Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose). |
| Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10\^3/mm\^3): G1=1.5 to \<2.0, G2=1.0 to \<1.5, G3=0.5 to \< 1.0, G4=\<0.5. Hemoglobin (g/dL): G1=10.0 to \<12.0, G2=8.0 to \<10.0, G3=6.5 to \<8.0, G4=\< 6.5. Platelets (10\^3/microliter): G1=75 to \<150, G2=50 to \<75, G3=25 to \<50, G4=\<25. |
| Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10\^3/mm\^3): G1=1.5 to \<2.0, G2=1.0 to \<1.5, G3=0.5 to \< 1.0, G4=\<0.5. Hemoglobin (g/dL): G1=10.0 to \<12.0, G2=8.0 to \<10.0, G3=6.5 to \<8.0, G4=\< 6.5. Platelets (10\^3/microliter): G1=75 to \<150, G2=50 to \<75, G3=25 to \<50, G4=\<25. |
| Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report | Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13) | An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect. |
| Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13) | An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect. |
| Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13) | Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. |
| Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13) | The culture results could be positive or negative. The positive culture results indicates that the tested participant have the infection under investigation so therapeutic treatment with anti-infective is required. |
| Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13) | Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals. |
| Number of Participants Who Received Any Supportive Care After Fludarabine Treatment and After TST Treatment | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease. |
| Number of Participants With Any Adverse Event (AE) | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and does not necessarily have to have a causal relationship (association) with this treatment. Therefore, an AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not it was considered to be related to the medicinal product. Laboratory abnormalities were recorded as AEs only if they were associated with clinical sequelae and/or required an intervention. |
| Number of Participants With Any Treatment-related Adverse Event (TRAE) | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out. |
| Number of Participants With Any Grade 3 or Grade 4 Adverse Event | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. |
| Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | All of the treatment-related grade 3 (severe and undesirable) and grade 4 (life-threatening or disabling) adverse events experienced by the participants were recorded. |
| Number of Participants With Any Serious Adverse Event (SAE) | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | An SAE was defined as any event occurring at any dose that results in any of the following outcomes: death, a life threatening adverse drug experience (at immediate risk of death from the experience as it occurred), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious adverse drug experience when based upon appropriate medical judgment. |
| Number of Participants With Any Treatment-related SAE | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | All of the treatment-related SAEs experienced by the participants were recorded. |
| Number of Participants With the Indicated Grade 3 and Grade 4 AEs | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. mm, millimeters; mm\^3, millimeters cubed. Grade 3 and Grade 4 AEs are reported to focus on the most severe AEs. |
| Number of Participants With Thyroid Medication Use Prior to the Therapeutic Dose | Baseline (study entry; Week -16) and Week 2 to Week 3 (prior to the therapeutic dose) | Thyroid medication included any prescribed medication for the treatment of thyroid dysfunction. |
| Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520) | All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out. |
| Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24 | Day 1 to Day 730 (24 Months) after receiving the dosimetric dose | The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be positive, a participant had to have a positive HAMA assessment at any follow-up visit (Weeks 12 and 25; Months 12, 18, and 24). |
| Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity | Day 1 to Day 730 (24 Months) after receiving the dosimetric dose | Kaplan-Meier estimates of the time to HAMA positivity (days from the first fludarabine dose) was determined for participants who converted to HAMA positivity. |
| Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Baseline (Week -16) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | The number of participants with elevated TSH levels is reported. An elevated TSH level indicates that an insufficient amount of the thyroid hormone is being produced. Insufficient thyroid hormone production is known as hypothyroidism. The normal range of TSH is between 0.2 and 6.1 milliunits per liter (mU/L). |
| Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose) | Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose). |
| Nadir Values for Absolute Neutrophil Count (ANC) | up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose) | Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions. |
| Number of Participants With Progression of Disease | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | Progression of disease is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination. All participants without progression of disease were censored. |
| Duration of Response for All Confirmed Responders | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | Duration of response was defined as the time from the first documented response to the first documented disease progression. Partial Response (PR): 50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. Responders are the participants with CR, or CCR, or PR. |
| Number of Participants With Progressive Disease (PD) | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | PD is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination. |
| Time to Disease Progression or Death | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | Time to progression is the time from the treatment start date to the first documented disease progression or death. Disease progression: 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination. |
| Number of Participants With a Treatment Failure | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | Treatment failure is defined as the occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death. |
| Time to Treatment Failure | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | Time to treatment failure is defined as the time from the treatment start date to the first occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death. |
| Number of Participants Who Died During Their Participation in the Study | Day of TST/I 131 TST dosimetric dose to date of database release (Week 1 to Week 520); First day of fludarabine cycle 1 to date of database release (Week -16 to Week 520) | Participants who died during the study period were evaluated for the overall survival endpoint. |
| Time to Death of Participants During Their Participation in the Study | Day of TST/I 131 TST dosimetric dose to date of database release (Week 1 to Week 520); First day of fludarabine cycle 1 to date of database release (Week -16 to Week 520) | Time to death is defined as the time from the treatment start date to the date of death. |
| Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520) | CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions. A confirmed response (resp.) (CR/CCR/PR) had to be confirmed by a consecutive resp. (\>=28 days later) that was the same/better. Individual confirmed resp. data only counts that resp. confirmed by the same resp.; not all possible combinations are represented. |
Participant flow
Pre-assignment details
Participants received fludarabine in the first study phase. Upon completion of this phase, if they met the appropriate criteria, they began the first of 2 phases of radioimmunotherapy: Phase 1, dosimetric dose (DD), administered 6 weeks after Day 1 of the third fludarabine cycle; Phase 2, therapeutic dose, administered 7-14 days after the DD.
Participants by arm
| Arm | Count |
|---|---|
| Received Less Than 3 Cycles of Fludarabine Participants received less than 3 cycles of intravenous (IV) fludarabine monophosphate (25 milligrams/meter\^2/day \[mg/m\^2/day\]) for 5 days every 5 to 6 weeks. | 2 |
| Fludarabine (3 Cycles); TST and Iodine I 131 TST Participants (par.) received 3 cycles of IV fludarabine (FL) monophosphate (25 mg/m\^2/day) for 5 days every 5-6 weeks. After receiving FL, par. meeting criteria received the dosimetric dose (DD), administered 6-8 weeks after the 3rd cycle of FL. IV administration of unlabeled tositumomab (TST) (450 mg) was infused over 1 hour (hr) prior to a 30 minute infusion of 35 mg TST trace labeled with 5 millicurie (mCi) iodine I 131. Par. received \>=3 doses (4 drops by mouth \[DBM\], 3 times a day \[TID\]) of a saturated solution of potassium iodide (KI), 3 doses (20 DBM, TID) of Lugol's solution, or KI tablets (130 mg BM, once a day) \>=24 hrs prior to administration of the DD and continued daily for 14 days after the therapeutic dose (TD), administered 7-14 days after the DD. The TD was an IV infusion of 450 mg TST over 1 hr, followed by infusion of 35 mg of TST radiolabeled with iodine I 131 to deliver the appropriate total body dose of 75, 65, or 45 centigray (cGy) over 20 minutes. | 36 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Co-morbid Illness | 1 | 0 |
| Overall Study | Didn't Meet Criteria for TST/I 131 TST | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Progressive Disease | 0 | 11 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Received Less Than 3 Cycles of Fludarabine | Fludarabine (3 Cycles); TST and Iodine I 131 TST | Total |
|---|---|---|---|
| Age, Continuous | 61.0 Years STANDARD_DEVIATION 11.3 | 51.2 Years STANDARD_DEVIATION 13.4 | 51.7 Years STANDARD_DEVIATION 13.4 |
| Gender Female | 1 Participants | 16 Participants | 17 Participants |
| Gender Male | 1 Participants | 20 Participants | 21 Participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 2 participants | 34 participants | 36 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 38 | 34 / 35 | 38 / 38 |
| serious Total, serious adverse events | 2 / 38 | 7 / 35 | 8 / 38 |
Outcome results
Primary
Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets
Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10\^3/mm\^3): G1=1.5 to \<2.0, G2=1.0 to \<1.5, G3=0.5 to \< 1.0, G4=\<0.5. Hemoglobin (g/dL): G1=10.0 to \<12.0, G2=8.0 to \<10.0, G3=6.5 to \<8.0, G4=\< 6.5. Platelets (10\^3/microliter): G1=75 to \<150, G2=50 to \<75, G3=25 to \<50, G4=\<25.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fludarabine | Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | ANC | 31 days |
| Fludarabine | Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | Hemoglobin | 16 days |
| Fludarabine | Duration of Any Grade 3 or Grade 4 Toxicity for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | Platelets | 29 days |
Primary
Nadir Values for Absolute Neutrophil Count (ANC)
Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).
Time frame: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)
Population: ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fludarabine | Nadir Values for Absolute Neutrophil Count (ANC) | 0.8 10^3/mm^3 |
Primary
Nadir Values for Hemoglobin
Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).
Time frame: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)
Population: ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fludarabine | Nadir Values for Hemoglobin | 10.7 g/dL |
Primary
Nadir Values for Platelet Count
Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).
Time frame: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)
Population: ITT-Exposed Population: only the 35 participants who received the dosimetric dose were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fludarabine | Nadir Values for Platelet Count | 53 10^3/microliter |
Primary
Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment
Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease. Supportive care involved administration of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), red blood cell (RBC) transfusions, erythropoietin, and platelet transfusions.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population: two participants who received less than 3 cycles of fludarabine did not receive TST treatment and were not evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | Platelet transfusion | 3 participants |
| Fludarabine | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | RBC transfusion | 8 participants |
| Fludarabine | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | Erythropoietin | 7 participants |
| Fludarabine | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | G-CSF/GM-CSF | 10 participants |
| TST and Iodine I 131 TST | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | Platelet transfusion | 2 participants |
| TST and Iodine I 131 TST | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | G-CSF/GM-CSF | 10 participants |
| TST and Iodine I 131 TST | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | Erythropoietin | 7 participants |
| TST and Iodine I 131 TST | Number of Participants Receiving the Indicated Type of Supportive Care After Fludarabine Treatment and After TST Treatment | RBC transfusion | 7 participants |
Primary
Number of Participants Who Received Any Supportive Care After Fludarabine Treatment and After TST Treatment
Supportive care involves interventions that help the participants to achieve comfort but do not affect the course of a disease.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population: two participants who received less than 3 cycles of fludarabine did not receive TST treatment, and hence were not evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants Who Received Any Supportive Care After Fludarabine Treatment and After TST Treatment | 15 participants |
| TST and Iodine I 131 TST | Number of Participants Who Received Any Supportive Care After Fludarabine Treatment and After TST Treatment | 14 participants |
Primary
Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24
The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be positive, a participant had to have a positive HAMA assessment at any follow-up visit (Weeks 12 and 25; Months 12, 18, and 24).
Time frame: Day 1 to Day 730 (24 Months) after receiving the dosimetric dose
Population: ITT-Exposed Population: participants who were evaluable for HAMA (those who did not have a positive HAHA level at Baseline) and those who received dosimetric and therapeutic doses were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24 | Positive | 2 participants |
| Fludarabine | Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Study Entry) But Positive or Negative at Weeks 12 and 25 and at Months 12, 18, and 24 | Negative | 30 participants |
Primary
Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment
Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen.
Time frame: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 13 Post-TST Treatment, n=9 | 1 participants |
| Fludarabine | Number of Participants With a Culture Obtained for Infection at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fl treatment, n=11 | 2 participants |
Primary
Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment
Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.
Time frame: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fl treatment, n=11 | 11 participants |
| Fludarabine | Number of Participants With an Anti-infective Administered at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 13 Post-TST Treatment, n=9 | 9 participants |
Primary
Number of Participants With Any Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and does not necessarily have to have a causal relationship (association) with this treatment. Therefore, an AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not it was considered to be related to the medicinal product. Laboratory abnormalities were recorded as AEs only if they were associated with clinical sequelae and/or required an intervention.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: Intent-to-Treat (ITT)-Exposed Population: all participants who were enrolled into the study and who received at least 1 dose of fludarabine. The data are presented for the subgroup of the ITT-Exposed Population for those participants who received the dosimetric and therapeutic dose of TST/I 131 TST.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Any Adverse Event (AE) | 33 participants |
| TST and Iodine I 131 TST | Number of Participants With Any Adverse Event (AE) | 34 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With Any Adverse Event (AE) | 38 participants |
Primary
Number of Participants With Any Grade 3 or Grade 4 Adverse Event
Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Any Grade 3 or Grade 4 Adverse Event | 17 participants |
| TST and Iodine I 131 TST | Number of Participants With Any Grade 3 or Grade 4 Adverse Event | 30 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With Any Grade 3 or Grade 4 Adverse Event | 34 participants |
Primary
Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets)
Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades (G): 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE. ANC (10\^3/mm\^3): G1=1.5 to \<2.0, G2=1.0 to \<1.5, G3=0.5 to \< 1.0, G4=\<0.5. Hemoglobin (g/dL): G1=10.0 to \<12.0, G2=8.0 to \<10.0, G3=6.5 to \<8.0, G4=\< 6.5. Platelets (10\^3/microliter): G1=75 to \<150, G2=50 to \<75, G3=25 to \<50, G4=\<25.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST dosimetric dose (DD) (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) | ANC | 28 participants |
| Fludarabine | Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) | Hemoglobin | 10 participants |
| Fludarabine | Number of Participants With Any Grade 3 or Grade 4 Toxicity (AE) for Hematological Parameters (Absolute Neutrophil Count [ANC], Hemoglobin, and Platelets) | Platelets | 17 participants |
Primary
Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report
An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect.
Time frame: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report | Week 16 Post-Fludarabine Treatment | 11 participants |
| Fludarabine | Number of Participants With Any Infection at Week 16 Post-Fludarabine Treatment and Week 13 Post-TST Treatment Detected by Laboratory Culture of Participant Sample or Investigator Report | Week 13 Post-TST Treatment | 9 participants |
Primary
Number of Participants With Any Serious Adverse Event (SAE)
An SAE was defined as any event occurring at any dose that results in any of the following outcomes: death, a life threatening adverse drug experience (at immediate risk of death from the experience as it occurred), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious adverse drug experience when based upon appropriate medical judgment.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Any Serious Adverse Event (SAE) | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With Any Serious Adverse Event (SAE) | 7 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With Any Serious Adverse Event (SAE) | 8 participants |
Primary
Number of Participants With Any Treatment-related Adverse Event (TRAE)
All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Any Treatment-related Adverse Event (TRAE) | 32 participants |
| TST and Iodine I 131 TST | Number of Participants With Any Treatment-related Adverse Event (TRAE) | 34 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With Any Treatment-related Adverse Event (TRAE) | 38 participants |
Primary
Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event
All of the treatment-related grade 3 (severe and undesirable) and grade 4 (life-threatening or disabling) adverse events experienced by the participants were recorded.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event | 16 participants |
| TST and Iodine I 131 TST | Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event | 30 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With Any Treatment-related Grade 3 or Grade 4 Adverse Event | 34 participants |
Primary
Number of Participants With Any Treatment-related SAE
All of the treatment-related SAEs experienced by the participants were recorded.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Any Treatment-related SAE | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With Any Treatment-related SAE | 7 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With Any Treatment-related SAE | 7 participants |
Primary
Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512
The number of participants with elevated TSH levels is reported. An elevated TSH level indicates that an insufficient amount of the thyroid hormone is being produced. Insufficient thyroid hormone production is known as hypothyroidism. The normal range of TSH is between 0.2 and 6.1 milliunits per liter (mU/L).
Time frame: Baseline (Week -16) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512
Population: ITT-Exposed Population: baseline TSH levels were determined for 36 participants. Of 35 participants who received the dosimetric and therapeutic doses of TST/I-131 TST, 2 had elevated TSH at baseline, and 33 were assessed for developing elevated TSH.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Baseline (Week -16), n=35 | 2 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 25, n=33 | 3 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 52, n=33 | 1 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 78, n=33 | 4 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 104, n=33 | 3 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 130, n=33 | 1 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 156, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 182, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 208, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 234, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 260, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 286, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 312, n=33 | 1 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 364, n=33 | 1 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 416, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 468, n=33 | 0 participants |
| Fludarabine | Number of Participants With Elevated Thyroid-Stimulating Hormone (TSH) Levels at Baseline (Study Entry) and Weeks 25, 52, 78, 104, 130, 156, 182, 208, 234, 260, 286, 312, 364, 416, 468, and 512 | Week 512, n=33 | 0 participants |
Primary
Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment
The culture results could be positive or negative. The positive culture results indicates that the tested participant have the infection under investigation so therapeutic treatment with anti-infective is required.
Time frame: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses, those who had an infection, and from whom the cultures were obtained were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fl treatment, n=2 | 0 participants |
| Fludarabine | Number of Participants With Positive Culture Results for Infections at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 13 Post-TST Treatment, n=1 | 0 participants |
Primary
Number of Participants With the Indicated Grade 3 and Grade 4 AEs
AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. mm, millimeters; mm\^3, millimeters cubed. Grade 3 and Grade 4 AEs are reported to focus on the most severe AEs.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Platelet count <50000 cells/mm^3 | 3 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Left ventricular dysfunction | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Acute myeloid leukaemia | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Dyspnoea | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Cardiac failure congestive | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Chronic myelomonocytic leukaemia | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Prostate cancer | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Anaemia | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Squamous cell carcinoma | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | White blood cell count <2000 cells/mm^3 | 12 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Arrhythmia | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Nausea | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Headache | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Leukopenia | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Absolute neutrophil count <1000 cells/mm^3 | 11 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Pyrexia | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Thrombocytopenia | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Hemoglobin <8.0 grams/deciliter | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Autoimmune thyroiditis | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Febrile neutropenia | 0 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Neutropenia | 7 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Myocardial infarction | 1 participants |
| Fludarabine | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Myelodysplastic syndrome | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Neutropenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | White blood cell count <2000 cells/mm^3 | 26 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Platelet count <50000 cells/mm^3 | 17 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Absolute neutrophil count <1000 cells/mm^3 | 27 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Anaemia | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Leukopenia | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Thrombocytopenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Febrile neutropenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Myelodysplastic syndrome | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Acute myeloid leukaemia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Prostate cancer | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Squamous cell carcinoma | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Nausea | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Arrhythmia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Cardiac failure congestive | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Left ventricular dysfunction | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Myocardial infarction | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Autoimmune thyroiditis | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Pyrexia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Headache | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Dyspnoea | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Hemoglobin <8.0 grams/deciliter | 10 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Chronic myelomonocytic leukaemia | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Febrile neutropenia | 2 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Absolute neutrophil count <1000 cells/mm^3 | 31 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Myocardial infarction | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Thrombocytopenia | 3 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Prostate cancer | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Autoimmune thyroiditis | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Leukopenia | 4 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Hemoglobin <8.0 grams/deciliter | 11 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Pyrexia | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Anaemia | 4 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Dyspnoea | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Headache | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Arrhythmia | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Neutropenia | 9 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Nausea | 2 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Squamous cell carcinoma | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Chronic myelomonocytic leukaemia | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Acute myeloid leukaemia | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Platelet count <50000 cells/mm^3 | 19 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Cardiac failure congestive | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Myelodysplastic syndrome | 2 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | White blood cell count <2000 cells/mm^3 | 30 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Grade 3 and Grade 4 AEs | Left ventricular dysfunction | 1 participants |
Primary
Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen
All noxious and unintended responses to a study treatment related to any dose were considered as TRAEs. A response to a study treatment indicates that a causal relationship between a study drug and an adverse event was at least a reasonable possibility, i.e., the relationship cannot be ruled out.
Time frame: First day of fludarabine cycle 1 to day prior to TST and iodine I 131 TST DD (Week -16 to Week 1); Day of TST and iodine I 131 TST DD to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Palpitations | 1 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Rash | 6 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nasopharyngitis | 1 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Absolute neutrophil count <1000 cells/mm^3 | 11 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Ecchymosis | 1 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Fatigue | 7 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Myalgia | 1 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Headache | 3 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Insomnia | 2 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Leukopenia | 3 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Dizziness | 0 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Sinusitis | 2 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Cough | 5 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Neutropenia | 11 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Pyrexia | 8 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Anaemia | 2 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Platelet count <50000 cells/mm^3 | 3 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Rhinorrhoea | 2 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Asthenia | 5 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | White blood cell count <2000 cells/mm^3 | 12 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Oropharyngeal pain | 2 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Chills | 3 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Decreased appetite | 6 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Dyspnoea | 2 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nausea | 12 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Hemoglobin <8.0 grams/deciliter | 1 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nasal congestion | 4 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Arthralgia | 0 participants |
| Fludarabine | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Vomiting | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Myalgia | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Absolute neutrophil count <1000 cells/mm^3 | 27 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | White blood cell count <2000 cells/mm^3 | 26 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Platelet count <50000 cells/mm^3 | 17 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Hemoglobin <8.0 grams/deciliter | 10 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Fatigue | 11 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Pyrexia | 10 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Asthenia | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Chills | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nausea | 9 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Vomiting | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Rash | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Ecchymosis | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Headache | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Dizziness | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Neutropenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Anaemia | 9 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Leukopenia | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Arthralgia | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Cough | 10 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nasal congestion | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Dyspnoea | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Oropharyngeal pain | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Rhinorrhoea | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Sinusitis | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Insomnia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nasopharyngitis | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Decreased appetite | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Palpitations | 3 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Decreased appetite | 10 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Cough | 14 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Vomiting | 7 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nasopharyngitis | 4 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nasal congestion | 8 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Chills | 6 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Platelet count <50000 cells/mm^3 | 19 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Dyspnoea | 6 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Asthenia | 9 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Palpitations | 4 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Oropharyngeal pain | 6 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Pyrexia | 14 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | White blood cell count <2000 cells/mm^3 | 30 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Rhinorrhoea | 4 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Fatigue | 16 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Insomnia | 4 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Neutropenia | 12 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Sinusitis | 5 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Dizziness | 5 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Anaemia | 10 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Headache | 8 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Absolute neutrophil count <1000 cells/mm^3 | 31 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Leukopenia | 5 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Ecchymosis | 5 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Rash | 8 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Myalgia | 5 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Nausea | 18 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Hemoglobin <8.0 grams/deciliter | 11 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Indicated Treatment-related AEs Experienced by at Least 10% of Participants in the Combined Regimen | Arthralgia | 4 participants |
Primary
Number of Participants With Thyroid Medication Use Prior to the Therapeutic Dose
Thyroid medication included any prescribed medication for the treatment of thyroid dysfunction.
Time frame: Baseline (study entry; Week -16) and Week 2 to Week 3 (prior to the therapeutic dose)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses were evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Thyroid Medication Use Prior to the Therapeutic Dose | 0 participants |
Primary
Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment
An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, bacteria, and viroids, although larger organisms such as macroparasites and fungi can also infect.
Time frame: Week 16 Post-Fludarabine Treatment (Week -16 to Week 0); Week 13 Post-TST Treatment (Week 1 to Week 13)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and those who had an infection were evaluated. A single participant could have had more than one infection. The number analyzed in the category titles reflects the number of participants who had any infection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fl treatment, Pneumonia, n=11 | 1 number of infections |
| Fludarabine | Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 16 Post-Fl treatment, Other Infections, n=11 | 12 number of infections |
| Fludarabine | Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 13 Post-TST Treatment, Pneumonia, n=9 | 0 number of infections |
| Fludarabine | Number of the Indicated Type of Infection Reported by Investigator Based on Laboratory Testing at Week 16 Post-Fludarabine (Fl) Treatment and Week 13 Post-TST Treatment | Week 13 Post-TST Treatment, Other Infections, n=9 | 9 number of infections |
Primary
Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity
Kaplan-Meier estimates of the time to HAMA positivity (days from the first fludarabine dose) was determined for participants who converted to HAMA positivity.
Time frame: Day 1 to Day 730 (24 Months) after receiving the dosimetric dose
Population: ITT-Exposed Population: participants who received dosimetric and therapeutic doses and those who were converted to HAMA positivity were evaluated.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Fludarabine | Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity | Participant 2 | 195 days | — |
| Fludarabine | Time to HAMA Positivity From the First TST/I 131 TST Dosimetric Dose for the Participants Achieving HAMA Positivity | Participant 1 | 184 days | 7.8 |
Primary
Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets
Nadir was defined as the lowest laboratory value recorded up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose).
Time frame: up to 120 days following the therapeutic dose (or dosimetric dose for participants who did not receive the therapeutic dose)
Population: ITT-Exposed Population: all participants who received the dosimetric dose were evaluated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fludarabine | Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | ANC | 48 days |
| Fludarabine | Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | Platelets | 36 days |
| Fludarabine | Time to Nadir for Hematological Parameters: Absolute Neutrophil Count (ANC), Hemoglobin, and Platelets | Hemoglobin | 50 days |
Secondary
Duration of Response for All Confirmed Responders
Duration of response was defined as the time from the first documented response to the first documented disease progression. Partial Response (PR): 50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. Responders are the participants with CR, or CCR, or PR.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population: all participants who received dosimetric and therapeutic doses and were classified as responders were evaluated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fludarabine | Duration of Response for All Confirmed Responders | Participants with CR, CCR, or PR, n=30, 32 | NA months |
| Fludarabine | Duration of Response for All Confirmed Responders | Participants with PR, n=1, 2 | 8.1 months |
| Fludarabine | Duration of Response for All Confirmed Responders | Participants with CR or CCR, n=29, 29 | NA months |
| TST and Iodine I 131 TST | Duration of Response for All Confirmed Responders | Participants with CR, CCR, or PR, n=30, 32 | NA months |
| TST and Iodine I 131 TST | Duration of Response for All Confirmed Responders | Participants with PR, n=1, 2 | 9.4 months |
| TST and Iodine I 131 TST | Duration of Response for All Confirmed Responders | Participants with CR or CCR, n=29, 29 | NA months |
Secondary
Number of Participants Who Died During Their Participation in the Study
Participants who died during the study period were evaluated for the overall survival endpoint.
Time frame: Day of TST/I 131 TST dosimetric dose to date of database release (Week 1 to Week 520); First day of fludarabine cycle 1 to date of database release (Week -16 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants Who Died During Their Participation in the Study | 9 participants |
| TST and Iodine I 131 TST | Number of Participants Who Died During Their Participation in the Study | 11 participants |
Secondary
Number of Participants With a Treatment Failure
Treatment failure is defined as the occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With a Treatment Failure | 20 participants |
| TST and Iodine I 131 TST | Number of Participants With a Treatment Failure | 23 participants |
Secondary
Number of Participants With Progression of Disease
Progression of disease is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination. All participants without progression of disease were censored.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population: participants with confirmed response rates (CR, CCR, or PR) were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With Progression of Disease | Progressed | 11 participants |
| Fludarabine | Number of Participants With Progression of Disease | Censored | 19 participants |
| TST and Iodine I 131 TST | Number of Participants With Progression of Disease | Progressed | 13 participants |
| TST and Iodine I 131 TST | Number of Participants With Progression of Disease | Censored | 19 participants |
Secondary
Number of Participants With Progressive Disease (PD)
PD is defined as a 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine | Number of Participants With Progressive Disease (PD) | 19 participants |
| TST and Iodine I 131 TST | Number of Participants With Progressive Disease (PD) | 21 participants |
Secondary
Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions. A confirmed response (resp.) (CR/CCR/PR) had to be confirmed by a consecutive resp. (\>=28 days later) that was the same/better. Individual confirmed resp. data only counts that resp. confirmed by the same resp.; not all possible combinations are represented.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population. 2 participants (par.) who received \<3 cycles of fludarabine (fl.) did not receive TST treatment and were not evaluated. Par. evaluable for response were those with \>=1 assessment. Three par. were not evaluable for response. None of the responses could be confirmed after fl. treatment; thus, no data are reported for this arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with PR | 0 participants |
| Fludarabine | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR, CCR, or PR | 0 participants |
| Fludarabine | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR or CCR | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR, CCR, or PR | 30 participants |
| TST and Iodine I 131 TST | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR or CCR | 29 participants |
| TST and Iodine I 131 TST | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with PR | 1 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR, CCR, or PR | 32 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with PR | 2 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Investigator-assessed Confirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR or CCR | 29 participants |
Secondary
Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
CR: Complete resolution of disease-related (DR) radiological abnormalities; disappearance of non-Hodgkin's lymphoma-related signs/symptoms. CCR: Complete resolution of DR symptoms except for residual scar tissue. PR: 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions with no new lesions.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population. Participants (par.) evaluable for response were those with \>= 1 response assessment. 2 of 38 par. who received \<3 cycles of fludarabine withdrew from the study and were not evaluable for response. 35 of 38 par. received TST and I 131 TST treatment and were evaluated for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fludarabine | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with PR | 29 participants |
| Fludarabine | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR or CCR | 3 participants |
| Fludarabine | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR, CCR, or PR | 32 participants |
| TST and Iodine I 131 TST | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with PR | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR, CCR, or PR | 32 participants |
| TST and Iodine I 131 TST | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR or CCR | 30 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with PR | 6 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR or CCR | 30 participants |
| Fludarabine/TST and Iodine I 131 TST (Combined Regimen) | Number of Participants With the Investigator-assessed Unconfirmed Responses of Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | Participants with CR, CCR, or PR | 36 participants |
Secondary
Time to Death of Participants During Their Participation in the Study
Time to death is defined as the time from the treatment start date to the date of death.
Time frame: Day of TST/I 131 TST dosimetric dose to date of database release (Week 1 to Week 520); First day of fludarabine cycle 1 to date of database release (Week -16 to Week 520)
Population: ITT-Exposed Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fludarabine | Time to Death of Participants During Their Participation in the Study | NA months |
| TST and Iodine I 131 TST | Time to Death of Participants During Their Participation in the Study | NA months |
Secondary
Time to Disease Progression or Death
Time to progression is the time from the treatment start date to the first documented disease progression or death. Disease progression: 50% increase from nadir of the sum of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter per radiographic evaluation or \>1 cm in diameter by physical examination.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population. Participants with disease progression were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fludarabine | Time to Disease Progression or Death | 97.5 months |
| TST and Iodine I 131 TST | Time to Disease Progression or Death | 95.6 months |
Secondary
Time to Treatment Failure
Time to treatment failure is defined as the time from the treatment start date to the first occurrence of treatment withdrawal, a decision to seek additional therapy, study removal, progression, alternative therapy for lymphoma, or death.
Time frame: First day of fludarabine cycle 1 to day prior to TST/I 131 TST dosimetric dose (Week -16 to Week 1); Day of TST/I 131 TST dosimetric dose to database release (Week 1 to Week 520)
Population: ITT-Exposed Population. Participants with treatment failure were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fludarabine | Time to Treatment Failure | 91.4 months |
| TST and Iodine I 131 TST | Time to Treatment Failure | 50.0 months |