Safety and Efficacy Study of I-131 Tositumomab in Patients With Relapsed/Refractory Hodgkin's Lymphoma

A Phase I/II Study of I-131 Tositumomab in Patients With Relapsed/Refractory Hodgkin's Lymphoma

The purpose of this study is to find the highest safe dose of Iodine-131 Tositumomab (Bexxar®) that can be given to patients who have relapsed/refractory Hodgkin's lymphoma, what side effects these patients get when they take Bexxar® and if Bexxar® is effective in treating relapsed/refractory Hodgkin's lymphoma. Bexxar® works by delivering doses of radiation to cancer cells.

Study Overview

• Status: Completed
• Conditions: Hodgkin's Disease
• Intervention / Treatment: Drug: I-131 Tositumomab therapeutic regimen

Detailed Description

One third of patients with Hodgkin's lymphoma (HL) do not respond to or have their disease come back after their first therapy. These patients often then receive high-dose chemotherapy and blood or marrow transplant. Despite high response rates after transplant, a significant number, 26-65%, of these patients have their disease come back again. After transplant, therapy options are limited and alternative therapies for patients with HL who have relapsed post-transplant or who are ineligible for transplant are needed. Based on recent studies about how HL develops and good results of patient studies evaluating the use of the unlabeled anti-CD20 antibody Rituximab in HL, we think that radioimmunotherapy (RIT) with I-131 Tositumomab(Bexxar®) will be an effective alternative therapy in patients with relapsed/refractory HL who are post or ineligible for transplant.

The rationale for the use of RIT in cancer is that radiolabeled monoclonal antibodies will specifically target and irradiate tumor cells but not normal tissues. The specific tumor targeting of RIT theoretically allows higher doses of radiation to be delivered to tumor as compared to external beam radiation because the effects of the radiation on normal tissues is less with RIT. Iodine-131 Tositumomab (Bexxar®) was approved by the FDA for another type of lymphoma in 2003. The antibody (Tositumomab) recognizes and attaches to a protein on lymphoma cells and can kill these cells. The radioisotope (I-131) can help the antibody kill cells better.

Iodine-131 Tositumomab (Bexxar®) is given through a vein in the arm. Iodine-131 Tositumomab (Bexxar®) is given in an outpatient setting.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medical Institutions

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:

• Biopsy-proven Hodgkin's lymphoma that is relapsed or refractory and the patient has previously had a transplant or is ineligible for transplant
• All stages and histologic subtypes of Hodgkin's lymphoma
• Malignant cells may be CD20+ or CD20-
• May have previously had either a non-myeloablative or myeloablative allogeneic or autologous stem cell transplant
• If prior history of greater than 1 transplant, eligible if other entry criteria are met
• No upper limit on the amount of prior chemotherapy
• Must be at least 4 weeks out from their most recent chemotherapy or radiation therapy, 6 weeks if the last regimen included BCNU, or mitomycin
• Age 18 or greater
• Karnofsky performance status ≥ 60
• Organ and marrow function within 4 weeks of registration on the protocol as defined below:
• Leukocytes >2,000/mm3
• Absolute neutrophil count >1,000/ mm3
• Platelets >75,000/ mm3
• Hemoglobin >7 g/dL
• Creatinine <2.5 mg/dL
• Less than 25% bone marrow involvement with Hodgkin's lymphoma within 4 weeks of registration on the protocol
• If female, not pregnant or breast feeding
• Ability to understand and the willingness to sign a written informed consent document
• At least one measurable target lesion, measuring 1.5 cm in at least one dimension by standard CT imaging which is FDG -avid on PET/CT.
• 2-year expected survival from other diseases

Exclusion Criteria:

• Receiving any other investigational agents at the same time
• Hypocellular bone marrow (less than or equal to 10% cellularity) or marked decrease in any one (or more) hematopoietic precursor within 4 weeks of registration on the protocol
• Inability to follow basic radiation safety precautions
• Active infections requiring intravenous antibiotics until after resolution of the infection

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: A Single Dose of I-131 Tositumomab; I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant.	Drug: I-131 Tositumomab therapeutic regimen; Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.; Other Names: Brand name: Bexxar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-myeloablative Maximum Tolerated Dose of I-131 Tositumomab That Can be Given to Patients With Relapsed/Refractory Hodgkin's Lymphoma.		2 years
Overall and Complete Response Rates	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CTI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	12 weeks post therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Progression Following I-131 Tositumomab Therapy.		From time measurement criteria are met for response until first date that recurrent or progressive disease is objectively documented, assessed up to 5 years.
Frequency of Visualization of Hodgkin's Lymphoma With I-131 Tositumomab Imaging and Tumor Radiation Absorbed Dose	Percentage of participants with visualized I-131 uptake.	up to 1 week post-intervention

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Richard L Wahl, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: June 8, 2007
• First Submitted That Met QC Criteria: June 8, 2007
• First Posted (Estimate): June 11, 2007

Study Record Updates

• Last Update Posted (Actual): August 1, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Safety; Monoclonal antibody; Efficacy; Hodgkin's lymphoma; Radioimmunotherapy; Bexxar; Nuclear Medicine; Radiolabeled; I-131 Tositumomab
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Antineoplastic Agents; Tositumomab I-131
• Other Study ID Numbers: J0703; NA_00005743 (Other Identifier: JHM IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No