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

NCT00268983 | Completed Phase 3 Results

• 1 other identifier: 393229/028
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 3

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.

Conditions

Lymphoma, Non-Hodgkin

Keywords

rituximab; tositumomab and iodine I 131 tositumomab; non-Hodgkins lymphoma; radioimmunotherapy; anti-B1 antibody; Bexxar; NHL; Tositumomab

Outcome Measures

Primary Outcomes (2)

• Event-free Survival (EFS)

  Event-free survival is defined as the time from the date of randomization to the first occurrence of (whichever came first) progressive disease, death, or additional Non-Hodgkins Lymphoma (NHL) therapy due to disease-related symptoms, threatened end-organ function, cytopenias secondary to NHL, massive bulk disease, or steady progression over at least 6 months. Progressive disease 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.

  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)

• Progression-free Survival

  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.

  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 (16)

• Number of Participants Achieving Response

  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

• Duration of Response

  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

• Time to Death

  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)

• Number of Participants Who Had Died by the Month Indicated

  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)

• Time to Next Treatment

  Time from study randomization to 120 days after study drug administration

Study Arms (2)

Tositumomab and Iodine I 131 Tositumomab

EXPERIMENTAL

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.

Biological: Tositumomab and Iodine I 131 Tositumomab

Rituximab

ACTIVE COMPARATOR

Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks.

Biological: Rituximab

Interventions

Tositumomab and Iodine I 131 Tositumomab BIOLOGICAL

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.

Also known as: Bexxar Therapeutic Regimen, anti-B1 Antibody, Iodine I 131 Tositumomab

Tositumomab and Iodine I 131 Tositumomab

Rituximab BIOLOGICAL

Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks.

Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Walla Walla, Washington, 99362, United States

Location

GSK Investigational Site

Pierre-Bénite, 69495, France

Location

GSK Investigational Site

Manchester, Lancashire, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24898665 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

tositumomab I-131; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2005
• First Posted: December 23, 2005
• Study Start: October 1, 2004
• Primary Completion: September 1, 2009
• Study Completion: June 1, 2013
• Last Updated: January 9, 2017
• Results First Posted: August 2, 2010

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

FR (1); GB (1); US (1)