Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00268983

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 III

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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Cadexomer iodine Rituximab Tositumomab Immunoglobulins Iodine Sodium iodide I 131 Globulin, Immune

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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: Bexxar Therapeutic Regimen anti-B1 Antibody Iodine I 131 Tositumomab
Active Comparator: Rituximab	Biological: Rituximab Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks. Other Name: Rituximab

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:

Bexxar Therapeutic Regimen
anti-B1 Antibody
Iodine I 131 Tositumomab

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00268983

Locations

United States, Washington
GSK Investigational Site
Walla Walla, Washington, United States, 99362
United Kingdom
GSK Investigational Site
Manchester, Lancashire, United Kingdom

Sponsors and Collaborators

GlaxoSmithKline

Investigators

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
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
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 February 09, 2012