Clinical trial NCT00268983: Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
Official title: A Multi-Center, Randomized, Phase 3 Study of Rituximab Versus Iodine I 131 Tositumomab Therapeutic Regimen For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Non-Hodgkin
Keywords: rituximab
tositumomab and iodine I 131 tositumomab
non-Hodgkins lymphoma
radioimmunotherapy
anti-B1 antibody
Bexxar
NHL
Tositumomab
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-12-23
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Comparison of rituximab versus Iodine I 131 Tositumomab Therapeutic Regimen (Tositumomab and Iodine I 131 Tositumomab or the Bexxar Therapeutic Regimen, formerly called Iodine-131 Anti-B1 Antibody) in subjects with follicular non Hodgkins B cell lymphoma. 506 subjects will be enrolled at 30 to 40 sites in the US, Canada, and Europe. Subjects will be randomly assigned to one of two treatment arms. In Arm A, subjects will receive 375 milligrams/meter2 (mg/m2 )of rituximab, given as an intravenous (IV) infusion once weekly for 4 weeks. In Arm B, subjects will undergo a two-phase treatment. In the first phase, termed the "dosimetric dose," subjects will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of 5 millicuries (mCi) (0.18 gigabecquerel \[GBq\]) of Iodine 131 Tositumomab (35 mg). Whole body gamma camera scans will be obtained three times (Day 0; Day 2, 3, or 4; and Day 6 or 7) following the dosimetric dose. The information derived from the scans will enable a patient specific dose to be calculated to deliver the desired total body dose of radiation (65 or 75 centigray \[cGy\]). In the second phase, termed the "therapeutic dose," subjects in Arm B will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of the subject specific activity of Iodine 131-conjugated Tositumomab (35 mg). Thyroid blockade will be implemented 24 hours prior to the dosimetric dose and continued for 14 days following the therapeutic dose. Subjects on study will be followed for response and safety at Week 7, Week 13, and every three months for the first and second year, every six months for the third year, and then annually for the forth and fifth years; and then for vital status, additional therapy, and long term safety events through year ten. Follow Up after subsequent NHL therapy will be carried out to assess tolerance of next anti-lymphoma therapy, development of myelodysplasia (MDS)/acute myelogenous leukemia (AML), HAMA or hypothyroidism, unexpected safety issues, and death.


Eligibility criteria: Inclusion criteria:

* Histologically confirmed diagnosis of follicular lymphoma
* Recurrent lymphoma after one or two qualifying therapy regimen(s)
* Patients must not have progressed within 4 weeks of their last chemotherapy dose
* Rituximab may have been used once as a single agent, in one continuous course of 4-8 weekly infusions (10-week period), or in combination with chemotherapy in a single prior treatment
* Patients whose prior therapy includes rituximab must have had a 6 month or greater response duration following the rituximab-containing regimen.
* Performance status of at least 70% on the Karnofsky Scale and an anticipated survival of at least three months
* Adequate absolute neutrophil count and platelet count within 21 days of study entry without support of blood products/growth factors
* Adequate renal function and adequate hepatic within 21 days of study entry
* Measurable disease, with at least one lesion measuring \>/=2.0 cm x 2.0 cm by CT scan
* Human Anti Mouse Antigen negative
* Written informed consent prior to study entry

Exclusion criteria:

* Histologic transformation to diffuse, large cell lymphoma.
* History of more than one course of Rituximab
* Disease limited to single lymph node or single group of nodes
* Involvement of 25% of the intratrabecular marrow by bone marrow biopsy specimen.
* Active infection requiring IV antibiotics at the time of study entry
* New York Heart Association Class III/IV heart disease
* Prior chemotherapy, biologic, radiation or steroid therapy for NHL within 8 weeks
* Any prior radioimmunotherapy
* Prior history of malignancy other than lymphoma (except for treated basal cell, squamous cell skin cancer, in situ cervical cancer, or other cancer that is disease-free for 5 years)
* Known HIV infection
* Hepatitis B positive
* Known central nervous system involvement

Primary outcomes:
measure: Event-free Survival (EFS)
timeFrame: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
measure: Progression-free Survival
timeFrame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Secondary outcomes:
measure: Number of Participants Achieving Response
timeFrame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually
measure: Duration of Response
timeFrame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually
measure: Time to Death
timeFrame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
measure: Number of Participants Who Had Died by the Month Indicated
timeFrame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
measure: Time to Next Treatment
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Hematologic Nadir for Absolute Neutrophil Count
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Hematologic Nadir for Hemoglobin
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Time to Nadir Values for the Indicated Hematological Parameters
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Time to Recovery to Baseline Grade for the Indicated Hematological Parameters
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters
timeFrame: Time from study randomization to 120 days after study drug administration
measure: Number of Participants That Developed Hypothyroidism
timeFrame: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
measure: Number of Participants With an Infusion Reaction
timeFrame: First 24 hours of study drug administration.
measure: Number of Hospitalizations
timeFrame: Time of treatment until 90 days post-treatment
measure: Number of Participants With Myelodysplasia/Leukemia
timeFrame: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
measure: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE)
timeFrame: From randomization through Week 26
Other outcomes:
Locations:
city: Walla Walla
country: United States
facility: GSK Investigational Site
state: Washington
city: Pierre-Benite Cedex
country: France
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Quackenbush RC, Horner TJ, Williams VC, Giampietro P, Lin TS. Patients with relapsed follicular lymphoma treated with rituximab versus tositumomab and iodine I-131 tositumomab. Leuk Lymphoma. 2015 Mar;56(3):779-81. doi: 10.3109/10428194.2014.927461. Epub 2014 Jul 23. No abstract available.