Hodgkin's Disease
Conditions
Keywords
Hodgkin's lymphoma, Radioimmunotherapy, Bexxar, I-131 Tositumomab, Safety, Efficacy, Nuclear Medicine, Monoclonal antibody, Radiolabeled
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.
Interventions
DRUGI-131 Tositumomab therapeutic regimen
Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.
Sponsors
GlaxoSmithKline
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | up to 1 week post-intervention | Percentage of participants with visualized I-131 uptake. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | A Single Dose of I-131 Tositumomab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 36 years |
| Post-transplant | 6 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 4 / 12 |
Outcome results
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A Single Dose of I-131 Tositumomab | Non-myeloablative Maximum Tolerated Dose of I-131 Tositumomab That Can be Given to Patients With Relapsed/Refractory Hodgkin's Lymphoma. | 79 cGy |
Primary
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.
Time frame: 12 weeks post therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A Single Dose of I-131 Tositumomab | Overall and Complete Response Rates | ORR | 25 percentage of participants |
| A Single Dose of I-131 Tositumomab | Overall and Complete Response Rates | CRR | 25 percentage of participants |
Secondary
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.
Time frame: up to 1 week post-intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A Single Dose of I-131 Tositumomab | Frequency of Visualization of Hodgkin's Lymphoma With I-131 Tositumomab Imaging and Tumor Radiation Absorbed Dose | 100 Percentage of patients with I-131 uptake |
Secondary
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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| A Single Dose of I-131 Tositumomab | Median Time to Progression Following I-131 Tositumomab Therapy. | 12 weeks | Standard Deviation 3.3 |