Study of Safety and Efficacy of a Sequential Regimen Consisting of Three Cycles of Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab

NCT ID: NCT00933335

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-08-31
• Study Completion Date: 2010-08-31

Brief Summary

This is a single-arm, single institution, phase II study of fludarabine monophosphate followed by Iodine I 131 Tositumomab for patients with previously untreated, advanced-stage (stage III or IV) low-grade, transformed low-grade and follicular non-Hodgkin's lymphoma. The primary objective of the study will be to evaluate the safety of this treatment combination and the secondary endpoint will be to evaluate efficacy.

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Patients will first receive an abbreviated course of three cycles of fludarabine (25 mg/m2 for 5 days every 5 weeks). Iodine I 131 tositumomab will be initiated 6 to 8 weeks after completion of fludarabine. Patients will undergo dosimetry studies to determine the appropriate patient-specific activity of iodine I 131 tositumomab required to deliver a fixed dose of 75 cGy. The dose will be attenuated to 65 cGy for patients with platelet counts between 100,000 and 150,000/micoliter.

Group Type: EXPERIMENTAL

Tositumomab and Iodine I 131 Tositumomab

Intervention Type: BIOLOGICAL

Tositumomab and Iodine I 131 Tositumomab

Interventions

Tositumomab and Iodine I 131 Tositumomab

Tositumomab and Iodine I 131 Tositumomab

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients must be age 18 years or older.
• Patients must have a histologically-confirmed diagnosis of low-grade or follicular non-Hodgkin's B-cell lymphoma.
• Patients must have Ann Arbor stage III or IV extent of disease after completing staging.
• Patients must have bi-dimensionally measurable disease. At least one lesion must have both perpendicular diameters > 2 cm.
• Patients must have evidence that their tumor expresses the CD20 antigen by immunohistochemistry or flow cytometry.
• Patients must have no previous treatment for NHL.
• Patients must have a Karnofsky performance status of at least 60% and an anticipated survival of at least 3 months.
• Patients must have absolute granulocyte count greater than or equal to 1500 cells/mm3 and a platelet count > 100,000 cells/mm3 within 14 days of study entry and not require sustained support with hematopoietic cytokines or transfusion of blood products.
• Patients must have adequate renal and hepatic function.
• Patients must sign IRB approved informed consent form(s) prior to study entry.

• Patients who completed 3 cycles of fludarabine.
• Patients must have absolute granulocyte count ≥ to 1500/mm3, platelet count of ≥ 100,000/mm3 (≥ 150,000/mm3 if > 25% bone marrow involvement at restaging), and not require sustained support with hematopoietic cytokines or transfusions with blood products.
• Patients must have adequate renal and hepatic function.

Exclusion Criteria

• Patients who received systemic steroids within 1 week of study entry, except patients on maintenance steroid therapy for a non-cancerous disease.
• Patients with evidence of active infection requiring intravenous antibiotics at the 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 known HIV Infection.
• Patients with known brain or leptomeningeal metastases.
• Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test at screening and on the day fludarabine treatment is started. Treatment is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the iodine I 131 tositumomab therapy.
• 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 hypersensitivity to fludarabine.
• Patients who are receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.
• Patients who are HAMA positive.
• Patients with previous allergic reaction to iodine. This does not include reacting to intravenous iodine containing contrast materials.

• Patients with active obstructive hydronephrosis.
• Patients with evidence of active infection requiring intravenous antibiotics.
• Patients who are pregnant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

References

Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005 Aug 20;23(24):5696-704. doi: 10.1200/JCO.2005.14.803.

Reference Type: RESULT

PMID: 16110029 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

http://jco.ascopubs.org/cgi/content/full/23/24/5696

Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman R, et al. Abbreviated Chemotherapy with Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab for Untreated Follicular Lymphoma. J Clin Oncol 2005;23:5696-5704

Other Identifiers

393229/023

Identifier Type: -

Identifier Source: org_study_id