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

Retreatment Study 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 treatment with Iodine-131 Anti-B1 Antibody for the retreatment of patients with non-Hodgkin's lymphoma who previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy. Patients will undergo two phases of study. In the first phase, patients will receive a dosimetric dose of unlabeled Anti-B1 Antibody (450 mg) followed by Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained after the dosimetric dose and data from three imaging time points will be used to calculate a patient-specific dose to deliver the desired total body dose of radiotherapy. In the second phase, patients will receive the therapeutic dose of unlabeled Anti-B1 Antibody (450 mg) followed by 35 mg of Anti-B1 Antibody labeled with the patient-specific dose to deliver the desired whole body dose of radiation. Patients will be treated with thyroid blocking medication at least 24 hours prior to the first infusion and continuing for 14 days following the last infusion.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Biological: Tositumomab and Iodine I 131 Tositumomab

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically confirmed initial diagnosis of non-Hodgkin's B-cell lymphoma
• Patients must have previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy
• Patients must have evidence that their tumor tissue had CD20 expression
• Patients must have performance status of at least 60% on the Karnofsky scale and an anticipated survival of at least 3 months
• Patients must have absolute granulocyte count (ANC) greater than 1,500 cells/mm3 and platelet count greater than 100,000 cells/mm3 within 14 days of study entry without support of hematopoietic cytokines or transfusion of blood products
• Patients must have adequate renal (serum creatine less than 1.5 x upper limit of normal) and hepatic function (total bilirubin less than 1.5 x upper limit of normal and hepatic transaminases, AST and ALT, less than 5 x upper limit of normal) within 14 days of study entry
• Patients must have bi-dimensionally measurable disease with a least one lesion greater than or equal to 2 cm x 2 cm by CT scan
• Patients must be at least 18 years of age
• Patients must give written informed consent and sign an Institutional Review Board/Ethics Committee- approved informed consent form prior to study entry

Exclusion Criteria:

• Patients with more than 25% bone marrow involvement
• Patients who have received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or who exhibit persistent clinical evidence of toxicity. The use of systemic steroids much be discontinued at least 1 week prior to study entry.
• Patients with active obstructive hydronephoresis
• Patients with evidence of active infection requiring IV antibiotics at time of study entry
• Patients with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation
• Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
• Patients with known HIV infection
• Patients with known brain or leptomeningeal metasteses
• Patients who are pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Retreatment of NHL with Iodine-131 Anti-B1 Antibody; Patients with non-Hodgkin's lymphoma who previously responded with a duration of response of at least 3 months to Iodine-131 Anti-B1 Antibody therapy will undergo two phases of study. In the first phase, patients will receive a dosimetric dose of unlabeled Anti-B1 Antibody (450 mg) followed by Anti-B1 Antibody (35 mg) which has been radiolabeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained after the dosimetric dose and data from three imaging time points will be used to calculate a patient-specific dose to deliver the desired total body dose of radiotherapy. In the second phase, patients will receive the therapeutic dose of unlabeled Anti-B1 Antibody (450 mg) followed by 35 mg of Anti-B1 Antibody labeled with the patient-specific dose to deliver the desired whole body dose of radiation. Patients will be treated with thyroid blocking medication at least 24 hours prior to the first infusion and continuing for 14 days following the last infusion.

Biological: Tositumomab and Iodine I 131 Tositumomab; Tositumomab and Iodine I 131 Tositumomab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Complete Response and Confirmed Complete Response	Complete response (CR) is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Response is defined as the best response achieved at any evaluation. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart.	Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Duration of Response for All Confirmed Responders (CR + CCR + PR)	For participants with CR, clinical CR (CCR), or partial response (PR), duration of response is defined as the time from the first documented response to the first documented progression. CCR is defined as the complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion <=2 centimeters (cm) in diameter by radiographic evaluation or <=1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations and, if unchanged or if further decreases for 6 months or longer are present, the participant will then be reclassified as a CR (complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease). PR is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.	Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Progression-free Survival	Progression-free survival (time to progression or death) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the first documented progression or death. Disease Progression (PD) is defined as a >=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be grater than 2 cm diameter by radiographic evaluation or grater than 1 cm diameter by physical examination.	Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Time to Treatment Failure	Time to treatment failure is defined as the time from the dosimetric dose to the first occurrence of treatment withdrawal, a decision to receive additional therapy, study withdrawal, disease progression, or death.	Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Overall Survival	Time to death (overall survival) is defined as the time from the start of retreatment (i.e., the dosimetric dose) to the date of death from any cause.	Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)
Number of Participants With Any Serious Adverse Event (SAE) and Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; or resulted in disability, congenital anomaly, or cancer. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.	Every 6 months until disease progression, death, or for 2 years following the dosimetric dose, whichever occurred first (average of 80.2 months)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): May 1, 2003
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 9, 2009
• First Submitted That Met QC Criteria: July 9, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Tositumomab I-131
• Other Study ID Numbers: 393229/010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 393229/010
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register