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

Primary Purpose

Hodgkin's Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

I-131 Tositumomab therapeutic regimen

About this trial

This is an interventional treatment trial for Hodgkin's Disease focused on measuring Hodgkin's lymphoma, Radioimmunotherapy, Bexxar, I-131 Tositumomab, Safety, Efficacy, Nuclear Medicine, Monoclonal antibody, Radiolabeled

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Johns Hopkins Medical Institutions

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A Single Dose of I-131 Tositumomab

Arm Description

I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant.

Outcomes

Primary Outcome Measures

Non-myeloablative Maximum Tolerated Dose of I-131 Tositumomab That Can be Given to Patients With Relapsed/Refractory Hodgkin's Lymphoma.

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.

Secondary Outcome Measures

Median Time to Progression Following I-131 Tositumomab Therapy.

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.

Full Information

NCT ID

NCT00484874

First Posted

June 8, 2007

Last Updated

July 31, 2018

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00484874

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

June 2007 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hodgkin's Disease

Keywords

Hodgkin's lymphoma, Radioimmunotherapy, Bexxar, I-131 Tositumomab, Safety, Efficacy, Nuclear Medicine, Monoclonal antibody, Radiolabeled

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A Single Dose of I-131 Tositumomab

Arm Type

Experimental

Arm Description

I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant.

Intervention Type

Drug

Intervention Name(s)

I-131 Tositumomab therapeutic regimen

Other Intervention Name(s)

Brand name: Bexxar

Intervention Description

Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.

Primary Outcome Measure Information:

Title

Non-myeloablative Maximum Tolerated Dose of I-131 Tositumomab That Can be Given to Patients With Relapsed/Refractory Hodgkin's Lymphoma.

Time Frame

2 years

Title

Overall and Complete Response Rates

Description

Time Frame

12 weeks post therapy

Secondary Outcome Measure Information:

Title

Median Time to Progression Following I-131 Tositumomab Therapy.

Time Frame

From time measurement criteria are met for response until first date that recurrent or progressive disease is objectively documented, assessed up to 5 years.

Title

Frequency of Visualization of Hodgkin's Lymphoma With I-131 Tositumomab Imaging and Tumor Radiation Absorbed Dose

Description

Percentage of participants with visualized I-131 uptake.

Time Frame

up to 1 week post-intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Richard L Wahl, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Medical Institutions

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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