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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00484874
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 101
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Disease	Drug: I-131 Tositumomab therapeutic regimen	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of I-131 Tositumomab in Patients With Relapsed/Refractory Hodgkin's Lymphoma
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Non-myeloablative Maximum Tolerated Dose of I-131 Tositumomab That Can be Given to Patients With Relapsed/Refractory Hodgkin's Lymphoma. [2 years]

2. Overall and Complete Response Rates [12 weeks post therapy]

   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

1. 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.]

2. Frequency of Visualization of Hodgkin's Lymphoma With I-131 Tositumomab Imaging and Tumor Radiation Absorbed Dose [up to 1 week post-intervention]

   Percentage of participants with visualized I-131 uptake.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Medical Institutions	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• GlaxoSmithKline

Investigators

• Principal Investigator: Richard L Wahl, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00484874
• Other Study ID Numbers: J0703; NA_00005743
• First Posted: Jun 11, 2007
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 2018

• 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
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Hodgkin's lymphoma; Radioimmunotherapy; Bexxar; I-131 Tositumomab; Safety; Efficacy; Nuclear Medicine; Monoclonal antibody; Radiolabeled
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Tositumomab I-131

Study Results

Participant Flow

Arm/Group Title	A Single Dose of I-131 Tositumomab
Arm/Group Description	I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	A Single Dose of I-131 Tositumomab
Arm/Group Description	I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	36
Sex: Female, Male (Count of Participants)
Female	6 50%
Male	6 50%
Post-transplant (Count of Participants)
Count of Participants [Participants]	6 50%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Single Dose of I-131 Tositumomab
Arm/Group Description	Non-myeloablative maximum tolerated dose of I-131 Tositumomab that can be given to patients with relapsed/refractory Hodgkin's lymphoma. I-131 Tositumomab therapeutic regimen: Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.
Measure Participants	12
Number [cGy]	79

2. Primary Outcome

Title	Overall and Complete Response Rates
Description	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.
Time Frame	12 weeks post therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Single Dose of I-131 Tositumomab
Arm/Group Description	A single therapeutic dosage of 131I-tositumomab. I-131 Tositumomab therapeutic regimen: Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.
Measure Participants	12
ORR	25 208.3%
CRR	25 208.3%

3. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A Single Therapeutic Dosage of 131I-tositumomab
Arm/Group Description	A single therapeutic dosage of 131I-tositumomab in patients who have undergone transplant. I-131 Tositumomab therapeutic regimen: Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.
Measure Participants	12
Median (Standard Deviation) [weeks]	12 (3.3)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	A single therapeutic dosage of 131I-tositumomab. I-131 Tositumomab therapeutic regimen: Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.
Measure Participants	12
Number [Percentage of patients with I-131 uptake]	100

Adverse Events

Time Frame	Adverse events were collected up to 2 years following the administration of I-131 Tositumomab.
Arm/Group Title	A Single Dose of I-131 Tositumomab
Arm/Group Description	I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant.
All Cause Mortality
	A Single Dose of I-131 Tositumomab
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	A Single Dose of I-131 Tositumomab
	Affected / at Risk (%)	# Events
Total	4/12 (33.3%)
Blood and lymphatic system disorders
Anemia	4/12 (33.3%)
Investigations
Hemoglobin Decreased	2/12 (16.7%)
Platelet Count Decreased	4/12 (33.3%)
Other (Not Including Serious) Adverse Events
	A Single Dose of I-131 Tositumomab
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Anemia	1/12 (8.3%)
Endocrine disorders
Hypothyroidism	2/12 (16.7%)
General disorders
Fatigue	5/12 (41.7%)
Fever	1/12 (8.3%)
Chills	1/12 (8.3%)
Cold Intolerance	1/12 (8.3%)
Infections and infestations
Lungm aero-digestive	1/12 (8.3%)
Investigations
Hemoglobin Decreased	6/12 (50%)
Platelet Count Decreased	6/12 (50%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	2/12 (16.7%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Hemorrhage	1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.