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Feasibility Study of External Beam Radiotherapy and Iodine-131 Tositumomab (Bexxar) for Patients With Relapsed Follicular Non-Hodgkin's Lymphoma

Phase 2
18 Years
Not Enrolling
Non-Hodgkin's Lymphoma, Follicular Lymphoma

Thank you

Trial Information

Feasibility Study of External Beam Radiotherapy and Iodine-131 Tositumomab (Bexxar) for Patients With Relapsed Follicular Non-Hodgkin's Lymphoma

Total dose delivered and tumor size are important predictors of local control in the
treatment of low-grade Non-Hodgkin's Lymphoma (NHL). The basic principle is that larger
nodal masses require increased doses of External Beam Radiotherapy (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 (PMID:11418315). He showed that tumors ≥15 cm^3 received only 1082
cGy with Zevalin, whereas the average dose delivered in tumors <15 cm^3 was 4763 cGy.
Recently, Gokhale et al (PMID: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 Non-Hodgkin's Lymphoma
(NHL), Koral et al (PMID: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 (PMID:10994741). The most compelling data
for this relationship comes from the clinical trials done using Bexxar. Both in the pivotal
trial (PMID:11579112) and the recently published trial treating naïve patients
(PMID: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

Whereas EBRT might be able to provide reliable radiation dose, the use of Bexxar may provide
the therapeutic equivalent of central lymphatic irradiation, 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.

Inclusion Criteria

Inclusion Criteria

- Relapsed Stage I-IV (no evidence of bone marrow involvement) Follicular Non-
Hodgkin's Lymphoma (NHF). Patients must have received at least 1 prior therapeutic
regimen of chemotherapy or Rituximab and demonstrated progression as demonstrated by

- One or more of the relapsed sites must be 5 cm or greater in dimension as assessed on
two dimensional imaging from CT or MRI scan.

- Biopsy at time of relapse confirming continued presence of CD 20 positive follicular

- No anti-cancer therapy for 3 weeks (six weeks if Rituximab, nitrosourea or Mitomycin
C) prior to study initiation, and fully recovered from all toxicities associated with
prior surgery, chemotherapy, or immunotherapy.

- An IRB-approved signed informed consent.

- Expected survival rate greater than 3 months.

- Prestudy performance status of 0 or 1 according to the World Health Organization
(WHO) criteria

- Acceptable hematologic status within two weeks prior to patient registration,

- Absolute neutrophil count (ANC) ([segmented neutrophils + bands] x total white
blood cells) greater than 1,500/mm^3

- Platelet counts greater than 100,000/mm^3

- Female patients who are not pregnant or lactating.

- Men and women of reproductive potential who are following accepted birth control
methods (as determined by the treating physician, however, abstinence is not an
acceptable method).

- Patients previously on Phase II drugs if no long-term toxicity is expected, and the
patient has been off the drug for eight or more weeks with no significant
post-treatment toxicities observed.

Exclusion Criteria

- Patients with impaired bone marrow reserve, as indicated by one or more of the

- Prior myeloablative therapies with bone marrow transplantation (either autologous or
allogeneic) or peripheral blood stem cell (PBSC) rescue.

- Platelet count > 100,000 cells/mm^3

- 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 follicular lymphoma (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 (central nervous system) involvement.

- Presence of primary Non-Hodgkin Lymphoma (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 (granulocyte colony-stimulating factor) or GM-CSF
(granulocyte-macrophage colony stimulating factor) therapy within two weeks prior to

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The Primary Endpoint of the Study Will be to Determine the Feasibility of Combining External Beam Radiotherapy (EBRT) and Bexxar by Assessing the Toxicities Associated With the Treatment.

Outcome Description:

13 patients will be enrolled initially and followed for 3 months. If less than 10 of these patients reach a grade III or IV toxicity, then 12 more patients will be enrolled and the study will be deemed feasible. If 11 or more of the first group experience grade III/IV toxicity, the trial will stop early.

Outcome Time Frame:

2 yr 3 mos

Safety Issue:


Principal Investigator

Robert J Amdur, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Florida


United States: Institutional Review Board

Study ID:

GSK Protocol #109407



Start Date:

September 2007

Completion Date:

April 2009

Related Keywords:

  • Non-Hodgkin's Lymphoma
  • Follicular Lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin



University of FloridaGainesville, Florida  32610-0277