| May 16, 2007 |
| September 5, 2007 |
| May 2007 |
| |
| The primary endpoint of the study will be to determine the feasibility of combining EBRT and Bexxar by assessing the toxicities associated with the treatment. |
| Same as current |
| Complete list of historical versions of study NCT00475332 on ClinicalTrials.gov Archive Site |
| The secondary endpoint will be to assess response rates and patterns of failure in patients treated with Bexxar and EBRT. |
| Same as current |
| |
| Study to Treat Relapsed Follicular Non-Hodgkin's Lymphoma With Radiation and Bexxar |
| Feasibility Study of External Beam Radiotherapy and Iodine-131 Tositumomab (Bexxar) for Patients With Relapsed Follicular Non-Hodgkin's Lymphoma |
The purpose of this study is to determine the feasibility of treating relapsed follicular lymphoma with a combination of Bexxar and EBRT. Patients will receive External Beam Radiation Therapy (20 Gy in 10 fractions) followed by Bexxar. |
Total dose delivered and tumor size are important predictors of local control in the treatment of low-grade NHL. The basic principle is that larger nodal masses require increased doses of EBRT to achieve local control. Radioimmunotherapy (RIT) seems to share this same characteristic. Review of the published literature on both Bexxar and Zevalin reveals that one of the most important predictors of treatment failure is nodal volume and its apparent relationship to dose delivered by RIT. The best tumor dosimetry for RIT is from Dr. Wiseman et al reporting on the dosimetry of Zevalin (11418315). He showed that tumors ≥15 cm3 received only 1082 cGy with Zevalin, whereas the average dose delivered in tumors <15 cm3 was 4763 cGy. Recently, Gokhale et al (16111589) published their experience with Zevalin at Cleveland Clinic and showed a significant correlation with pretreatment tumor volume and response to therapy. In their experience, tumors ≥5 cm had an 83% rate of local recurrence versus 28% for tumors <5 cm. This dosing paradox (bigger masses, which require more dose, receive less with RIT) may be diminished by the delivery of additional EBRT. This is the hypothesis that underlies the pilot study.
The dosimetric data available for Bexxar is more heterogeneous but confirms the observations seen with Zevalin. In patients previously untreated for low-grade NHL, Koral et al (12621015) showed an increased likelihood of achieving a complete response (CR) if tumor doses were >650 cGy. Previous work by these same authors showed a trend for larger tumor volumes receiving less dose (10994741). The most compelling data for this relationship comes from the clinical trials done using Bexxar. Both in the pivotal trial (11579112) and the recently published trial treating naïve patients (15689582), tumor volume was a significant predictor of response to Bexxar. In the pivotal trial, smaller tumor burden was the only factor predicting longer duration of response.
Whereas EBRT might be able to provide reliable radiation dose, the use of Bexxar may provide the therapeutic equivalent of CLI, which would permit the use of true involved field radiotherapy. Investigators have previously noted that increased EBRT field size is associated with increased short-term and long-term toxicity. The toxicities associated with the treatment of radiotherapy are related to the site treated, but do not necessarily include the dose limiting toxicity of Bexxar, which is primarily hematologic and transient. As the toxicity of RT and Bexxar may not overlap, the combination of both may allow an increase in the therapeutic window for both radiotherapy and Bexxar therapy. |
| Phase II |
| Interventional |
| Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study |
- Non-Hodgkin's Lymphoma
- Follicular Lymphoma
|
- Drug: Iodine I -01 Tositumomab (Bexxar)
- Procedure: External Beam Radiation Therapy
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| |
- Wiseman GA, White CA, Sparks RB, Erwin WD, Podoloff DA, Lamonica D, Bartlett NL, Parker JA, Dunn WL, Spies SM, Belanger R, Witzig TE, Leigh BR. Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. Crit Rev Oncol Hematol. 2001 Jul-Aug;39(1-2):181-94.
- Koral KF, Dewaraja Y, Li J, Lin Q, Regan DD, Zasadny KR, Rommelfanger SG, Francis IR, Kaminski MS, Wahl RL. Update on hybrid conjugate-view SPECT tumor dosimetry and response in 131I-tositumomab therapy of previously untreated lymphoma patients. J Nucl Med. 2003 Mar;44(3):457-64.
- Koral KF, Dewaraja Y, Li J, Barrett CL, Regan DD, Zasadny KR, Rommelfanger SG, Francis IR, Kaminski MS, Wahl RL. Initial results for Hybrid SPECT--conjugate-view tumor dosimetry in 131I-anti-B1 antibody therapy of previously untreated patients with lymphoma. J Nucl Med. 2000 Sep;41(9):1579-86.
- Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28.
- Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9.
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| |
| Recruiting |
| 25 |
|
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Inclusion Criteria
Exclusion Criteria
- Patients with impaired bone marrow reserve, as indicated by one or more of the following:
- Prior myeloablative therapies with bone marrow transplantation (either autologous or allogeneic) or peripheral blood stem cell (PBSC) rescue.
- Platelet count > 100,000 cells/mm3
- Hypocellular bone marrow
- Marked reduction in bone marrow precursors of one or more cell lines (granulocytic,megakaryocytic, erythroid).
- History of failed stem cell collection
- Presence of bone marrow involvement with FL > 25% based on bone marrow biopsy done within 2 months of enrollment.
- Evidence of transformation from original FL to a more aggressive NHL histology.
- Prior radioimmunotherapy.
- All relapsed sites are < 5 cm in dimension as assessed on two dimensional imaging from CT or MRI scan.
- Presence of CNS involvement.
- Presence of primary NHL of bone.
- Patients with HIV or AIDS-related lymphoma.
- Patients with abnormal renal function: serum creatinine > 2.0 mg/dL.
- Patients who have received prior external beam radiation therapy within three months of registration.
- Patients who have received G-CSF or GM-CSF therapy within two weeks prior to treatment.
- Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives.
- Major surgery, other than diagnostic surgery, within four weeks.
- Presence of anti-murine antibody (HAMA) reactivity.
|
| Both |
| 18 Years and older |
| No |
|
|
| United States |
| |
| NCT00475332 |
|
| GSK Protocol #109407 |
| University of Florida |
| GlaxoSmithKline |
| Principal Investigator: |
Kenneth Olivier, MD |
University of Florida |
|
|
| University of Florida |
| September 2007 |