Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
J0703
- SECONDARY ID:
NA_00005743
- NCT ID:
NCT00484874
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| I-131 Tositumomab therapeutic regimen | Brand name: Bexxar | A Single Dose of I-131 Tositumomab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| A Single Dose of I-131 Tositumomab | Experimental | I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant. | - I-131 Tositumomab therapeutic regimen
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Frequency of Visualization of Hodgkin's Lymphoma With I-131 Tositumomab Imaging and Tumor Radiation Absorbed Dose |
| Time Frame: | up to 1 week post-intervention |
| Safety Issue: | |
| Description: | Percentage of participants with visualized I-131 uptake. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- Hodgkin's lymphoma
- Radioimmunotherapy
- Bexxar
- I-131 Tositumomab
- Safety
- Efficacy
- Nuclear Medicine
- Monoclonal antibody
- Radiolabeled
Last Updated
August 1, 2018
