Advertisement

Topics

A Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL)

2014-08-27 04:00:34 | BioPortfolio

Summary

Subjects were randomized to receive either tositumomab (Anti-B1 Antibody) and iodine I 131 tositumomab (Arm A) or unlabeled tositumomab (Arm B). Subjects randomized to Arm B were allowed to cross over and receive I 131 tositumomab once their disease had progressed as long as they still fulfilled the protocol entry criteria (except for exclusion criterion 12, prior monoclonal antibody therapy) and were human anti-murine antibody (HAMA) negative. Study endpoint assessments of response were conducted by a Masked Independent Randomized Radiographic and Oncologic Review (MIRROR) panel and the Study Investigators' assessments of safety and survival. Subjects who completed at least two years of follow-up in Protocol BEX104515 (formerly Corixa Protocol RIT-II-002) were enrolled in long term follow-up Protocol BEX104526 (formerly Corixa Protocol CCBX001-051), an administrative protocol, for continued radiographic response evaluations and safety evaluations every 6 months for years 3 through 5 post-treatment and annually for years 6 through 10 post-treatment. Subjects in BEX104526 were assessed for survival, disease status, subsequent therapy for NHL, and long-term safety, including the use of thyroid medication, development of hypothyroidism, human anti murine antibody (HAMA), myelodysplastic syndrome, acute myelogenous leukemia, and all other secondary malignancies. Additionally, subjects were followed for the development of any adverse event(s) deemed by the Principal Investigator as being possibly or probably related to a subject's previous treatment with Iodine I-131 tositumomab. Laboratory evaluations consisting of a thyroid stimulating hormone level and a complete blood cell count, with a differential and platelet count, were obtained annually through year 10 post-treatment.

Dosimetric Dose: Subjects received 450 mg of tositumomab IV followed by 5.0 mCi of Iodine I-131 and 35 mg of tositumomab. Following the dosimetric dose, whole body dosimetry was performed on each subject using a total body gamma camera. Whole body anterior and posterior whole body images were obtained at the following timepoints.

1. Within one hour of infusion of the dosimetric dose and prior to urination

2. 2-4 days after infusion of the dosimetric dose, following urination

3. 6-7 days after infusion of the dosimetric dose, following urination Therapeutic Dose: The total body residence time, derived from total body gamma camera counts obtained at the 3 time points, was used to calculate the iodine-131 activity (mCi) to be administered to deliver the therapeutic total body irradiation dose of 65 or 75 cGy. The therapeutic step was administered 7-14 days after the dosimetric step and consisted of tositumomab 450 mg followed by an activity (mCi) of iodine-131 calculated to deliver 75 cGy or 65 cGy of total body irradiation, depending on platelet count, and 35 mg of tositumomab.

For subjects with ≥150,000 platelets/mm3, the recommended dose was the activity of iodine-131 calculated to deliver 75 cGy of total body irradiation; for subjects with NCI Grade 1 thrombocytopenia (platelet counts ≥100,000 but <150,000 platelets/mm3), the recommended dose was the activity of iodine-131 calculated to deliver 65 cGy of total body irradiation.

Description

This is a Phase II randomized, controlled, two-arm, open-label, multicenter study comparing the safety and efficacy of tositumomab and iodine I 131 tositumomab to tositumomab for the treatment of chemotherapy-relapsed or refractory low-grade or transformed low-grade B-cell NHL.

Treatment Arm A: Subject will undergo 2 phases of study. In the first phase, termed "dosimetric dose", subjects will receive tositumomab (450 mg) followed by tositumomab (35 mg) that has been trace labeled with 5mCi) Iodine-131 tositumomab. Whole body gamma camera scans will be obtained on day 0, day 2, 3, or 4, and day 6 or 7 following the dosimetric dose. Using the dosimetric data from three imaging time points, a subject-specific dose of iodine I 131 tositumomab to deliver the desired total body dose of radiotherapy will be calculated. In the second phase of the study, termed "therapeutic dose", subjects will receive unlabeled tositumomab (450mg) followed by iodine tositumomab (35mg) labeled with the subject-specific dose of iodine I-131 to deliver a whole body dose of 75 cGy to subjects. Subjects with platelet counts of 100,001 - 149,999 cells/mm3, will receive 65 cGy and subjects who are obese will be doses based on 137% of their lean body mass. Subjects will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion of the Iodine-131 tositumomab (i.e., the dosimetric dose) and continuing for 14 days following the last infusion of radiolabeled tositumomab (i.e., the therapeutic dose).

Treatment Arm B: Subjects will receive the same amount of unlabeled tositumomab (450 + 35 mg) administered over the same time-frame as Arm A on the study Days 0 and 7 (the day 7 dose may be delayed but no longer than 14 days after the first dose).

Crossover treatment Arm B: Subjects in Arm B may crossover and receive Iodine-131 tositumomab following progression of their lymphoma if they still fulfill the protocol inclusion exclusion criteria (except exclusion criteria#12) and are HAMA-negative.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Lymphoma, Non-Hodgkin

Intervention

Iodine-131 Anti-B1 Antibody Versus Anti-B1 Antibody in Chemotherapy-Relapsed/Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin's Lymphoma (NHL)

Status

Completed

Source

GlaxoSmithKline

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T04:00:34-0400

Clinical Trials [5141 Associated Clinical Trials listed on BioPortfolio]

Expanded Access Study of Iodine-131 Anti-B1 Antibody

The primary objective of this study is to make Iodine-131 Anti-B1 Antibody more broadly available to patients. Secondary endpoints of the study will be to obtain additional information on...

Safety and Efficacy of Iodine-131 Anti-B1 Antibody for Intermediate Grade Non-Hodgkin's Lymphoma Following First Line CHOP

The purpose of this study is to determine the safety and effectiveness of using Iodine-131 Anti-B1 Antibody for the treatment of patients with large B-cell non-Hodgkin's lymphoma (NHL) who...

Study of Iodine 131 Anti B1 Antibody for 1st or 2nd Relapsed Indolent B-Cell Lymphomas or B-Cell Lymphomas That Have Transformed to a More Aggressive Histology

This is a single-arm, open-label study of Iodine 131 Anti B1 Antibody for the treatment of 1st or 2nd relapsed indolent B cell lymphomas or B cell lymphomas that have transformed to a more...

Retreatment of Patients With Non-Hodgkin's Lymphoma Who Have Previously Responded to Iodine-131 Anti B1 Antibody

This multicenter study will determine the response rate, the complete response rate, duration of response, time to progression, time-to-treatment failure, safety, and survival following tr...

Safety and Efficacy Study of Iodine-131 Anti-B1 Antibody Plus CHOP For Untreated Mantle Cell Lymphoma

The purpose of this study is to test the safety of Iodine-131 Anti-B1 Antibody followed by CHOP and to see what effects it has on patients with previously untreated mantel cell lymphoma.

PubMed Articles [14503 Associated PubMed Articles listed on BioPortfolio]

Four cases of anti-Mi-2 antibody-positive dermatomyositis: relationship between anti-Mi-2 antibody titer and disease severity and activity.

Anti-Mi-2 antibody was found to be a specific marker for dermatomyositis (DM) [1, 2]. Patients with anti-Mi-2 antibody generally have a more favorable prognosis, such as milder muscle involvement and ...

Humanization of Murine Monoclonal anti-hTNF Antibody: The F10 Story.

Tumor necrosis factor (TNF) is a proinflammatory cytokine implicated in pathogenesis of multiple autoimmune and inflammatory diseases. Anti-TNF therapy has revolutionized the therapeutic paradigms of ...

Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results.

The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-str...

Presence of hepatitis B surface antibody in addition to hepatitis B core antibody confers protection against hepatitis B virus infection in hepatitis B surface antigen-negative patients undergoing kidney transplantation.

The American Gastroenterological Association (AGA) and European Association for the Study of the Liver (EASL) recommend that hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody ...

Development of Polyclonal Antibody against Clenbuterol for Immunoassay Application.

Development of an immunoassay for clenbuterol (CLB) detection required an anti-CLB antibody as an important bioreceptor. In this study, we report our work on production and purification of a rabbit-de...

Medical and Biotech [MESH] Definitions

Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.

A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)

An anti-VEGF recombinant monoclonal antibody consisting of humanized murine antibody. It inhibits VEGF receptors and prevents the proliferation of blood vessels.

The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.

A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.

More From BioPortfolio on "A Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL)"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Thyroid Disorders
The thyroid is a butterfly-shaped gland in the neck, just above thecollarbone and is an endocrine gland that make hormones. These Thyroid hormones control the rate of many activities in the body, including how fast the body burns calories and how fast th...

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...


Searches Linking to this Trial