Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma, Non-Hodgkin Non-Hodgkin's Lymphoma |
Biological: Tositumomab and Iodine I 131 Tositumomab Biological: Rituximab |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Progression-free Survival [ Time Frame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and Bexxar groups was 38.9 and 42.2 months, respectively) ] [ Designated as safety issue: No ]Progression-free survival is defined as the time from the initial date of dosing to the first documented disease progression or death. Disease assessment was based on the International Workshop to Standardize Response Criteria (IWSRC) for Non-Hodgkin's Lymphoma (NHL). Progression is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination.
- Number of Participants Achieving Response [ Time Frame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually ] [ Designated as safety issue: No ]Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms (by the IWSRC) if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Confirmation of response was carried out by an independent reviewer.
- Duration of Response [ Time Frame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually ] [ Designated as safety issue: No ]Response duration is defined as the time from the first documented response (complete response, complete response unconfirmed, or partial response) until disease progression. Partial response is defined as at least a 50% decrease in the product of two perpendicular diameters of all measurable lesions; no increase in the size of other nodes, liver, or spleen; and no new disease sites. As a median duration of response is not presented for either group, see the outcome measure entitled "Number of Participants with the Indicated Duration of Response" for data regarding duration of response.
- Number of Participants With the Indicated Duration of Response [ Time Frame: Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually ] [ Designated as safety issue: No ]The median duration of response could not be presented for participants in either treatment group; thus, data are shown as the number of participants with the indicated duration of response.
- Time to Death [ Time Frame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and Bexxar groups was 38.9 and 42.2 months, respectively) ] [ Designated as safety issue: No ]Time to death is defined as the time from treatment start to the date of death. As a median time to death is not presented for either treatment group, see the outcome measure entitled "Number of Participants Who Had Died by the Month Indicated" for data regarding time to death.
- Number of Participants Who Had Died by the Month Indicated [ Time Frame: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and Bexxar groups was 38.9 and 42.2 months, respectively) ] [ Designated as safety issue: No ]The median time to death could not be calculated for participants in either treatment group; thus, data are shown as the number of participants who had died by the month indicated.
| Enrollment: | 14 |
| Study Start Date: | October 2004 |
| Estimated Study Completion Date: | April 2016 |
| Primary Completion Date: | May 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Tositumomab and Iodine I 131 Tositumomab |
Biological: Tositumomab and Iodine I 131 Tositumomab
Dosimetric dose: 450 mg Tositumomab infused over 1 hour followed by 5 mCi I 131 Tositumomab infused over 20 minutes Therapeutic dose: 450 mg Tositumomab infused over 1 hour followed by Individualized mCi activity of I 131 Tositumomab (35 mg) infused over 20 minutes. Other Names:
|
| Active Comparator: Rituximab |
Biological: Rituximab
Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks.
Other Name: Rituximab
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Histologically confirmed diagnosis of follicular lymphoma
- Recurrent lymphoma after one or two qualifying therapy regimen(s)
- Patients must not have progressed within 4 weeks of their last chemotherapy dose
- Rituximab may have been used once as a single agent, in one continuous course of 4-8 weekly infusions (10-week period), or in combination with chemotherapy in a single prior treatment
- Patients whose prior therapy includes rituximab must have had a 6 month or greater response duration following the rituximab-containing regimen.
- Performance status of at least 70% on the Karnofsky Scale and an anticipated survival of at least three months
- Adequate absolute neutrophil count and platelet count within 21 days of study entry without support of blood products/growth factors
- Adequate renal function and adequate hepatic within 21 days of study entry
- Measurable disease, with at least one lesion measuring >/=2.0 cm x 2.0 cm by CT scan
- Human Anti Mouse Antigen negative
- Written informed consent prior to study entry
Exclusion criteria:
- Histologic transformation to diffuse, large cell lymphoma.
- History of more than one course of Rituximab
- Disease limited to single lymph node or single group of nodes
- Involvement of 25% of the intratrabecular marrow by bone marrow biopsy specimen.
- Active infection requiring IV antibiotics at the time of study entry
- New York Heart Association Class III/IV heart disease
- Prior chemotherapy, biologic, radiation or steroid therapy for NHL within 8 weeks
- Any prior radioimmunotherapy
- Prior history of malignancy other than lymphoma (except for treated basal cell, squamous cell skin cancer, in situ cervical cancer, or other cancer that is disease-free for 5 years)
- Known HIV infection
- Hepatitis B positive
- Known central nervous system involvement
Contacts and Locations| United States, Washington | |
| GSK Investigational Site | |
| Walla Walla, Washington, United States, 99362 | |
| United Kingdom | |
| GSK Investigational Site | |
| Manchester, Lancashire, United Kingdom | |
| Study Director: | GSK Clinical Trials, MD | GlaxoSmithKline |
More Information
No publications provided
| Responsible Party: | E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure |
| ClinicalTrials.gov Identifier: | NCT00268983 History of Changes |
| Other Study ID Numbers: | 393229/028, CCBX001-049 |
| Study First Received: | December 21, 2005 |
| Results First Received: | June 29, 2010 |
| Last Updated: | December 9, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by GlaxoSmithKline:
|
rituximab tositumomab and iodine I 131 tositumomab non-Hodgkins lymphoma radioimmunotherapy |
anti-B1 antibody Bexxar NHL Tositumomab |
Additional relevant MeSH terms:
|
Lymphoma, Non-Hodgkin Lymphoma Lymphoma, Follicular Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Antibodies Rituximab Antibodies, Monoclonal Iodine |
Cadexomer iodine Iodine-131 anti-B1 antibody Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Anti-Infective Agents, Local Anti-Infective Agents Therapeutic Uses Trace Elements Micronutrients Growth Substances Antirheumatic Agents Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 19, 2013