Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy

NCT ID: NCT00490490

Last Updated: 2017-03-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2013-07-31

Brief Summary

The purpose of the study is to assess the response rate of patients with relapsed or refractory low-grade or transformed low-grade, CD20-positive, B-cell non-Hodgkin's lymphoma to Iodine-131 (I-131) tositumomab (Bexxar) therapy plus local palliative radiation therapy (XRT).

Detailed Description

Response will be assessed on the basis of the presence or absence of measurable lesion ≥ 1.4 x 1.4 cm (operationally defined as ≥ 2.0 cm2) by radiographic evaluation OR ≥ 1.0 cm in greatest diameter detected by palpation on physical exam

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tositumomab + XRT + KI

Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)

Group Type: EXPERIMENTAL

Bexxar (tositumomab)

Intervention Type: DRUG

Tositumomab is a CD20-directed radiotherapeutic (131-iodine) monoclonal antibody indicated for the treatment of patients with CD20-positive, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin's lymphoma who have progressed during or after rituximab therapy, including patients with rituximab-refractory non-Hodgkin's lymphoma. Tositumomab (standard regimen) will be administered at whole body exposure of 75 cGy.

External beam radiotherapy (XRT)

Intervention Type: PROCEDURE

Patient-specific XRT will begin within 24 hours of administration of the therapeutic dose of tositumomab. Subjects will receive local XRT to bulky sites of disease measuring at least 5 cm in at least one dimension. The size and number of fields to be treated will determined by the investigators, but will encompass the patient's most symptomatic/threatening site(s) of disease and not cumulatively include more than 25% of the active bone marrow. Subjects will be treated with the 2 x 2 Gy regimen (2 daily fractions of 2 Gy). Sites of disease previously-irradiated with 30 to 40 Gy will not be treated on this study.

Potassium Iodide (KI)

Intervention Type: DRUG

Potassium iodide (KI) will be administered as:

• Saturated solution potassium iodide (SSKI) 4 drops orally 3-times-a-day,
• Lugol's solution 20 drops orally 3-times-a-day, OR
• KI tablets 130 mg orally once per day KI treatment will start at least 24 hours prior to tositumomab, and continue daily for 14 days following the last dose of tositumomab

Interventions

Bexxar (tositumomab)

Tositumomab is a CD20-directed radiotherapeutic (131-iodine) monoclonal antibody indicated for the treatment of patients with CD20-positive, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin's lymphoma who have progressed during or after rituximab therapy, including patients with rituximab-refractory non-Hodgkin's lymphoma. Tositumomab (standard regimen) will be administered at whole body exposure of 75 cGy.

Intervention Type: DRUG

External beam radiotherapy (XRT)

Patient-specific XRT will begin within 24 hours of administration of the therapeutic dose of tositumomab. Subjects will receive local XRT to bulky sites of disease measuring at least 5 cm in at least one dimension. The size and number of fields to be treated will determined by the investigators, but will encompass the patient's most symptomatic/threatening site(s) of disease and not cumulatively include more than 25% of the active bone marrow. Subjects will be treated with the 2 x 2 Gy regimen (2 daily fractions of 2 Gy). Sites of disease previously-irradiated with 30 to 40 Gy will not be treated on this study.

Intervention Type: PROCEDURE

Potassium Iodide (KI)

Potassium iodide (KI) will be administered as:

• Saturated solution potassium iodide (SSKI) 4 drops orally 3-times-a-day,
• Lugol's solution 20 drops orally 3-times-a-day, OR
• KI tablets 130 mg orally once per day KI treatment will start at least 24 hours prior to tositumomab, and continue daily for 14 days following the last dose of tositumomab

Intervention Type: DRUG

Other Intervention Names

131-iodine tositumomab; Radiotherapy (RT); Saturated Solution Potassium Iodide (SSKI); Lugol's solution; Potassium iodide tablets

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed low grade CD20+ B cell non-Hodgkin lymphoma (NHL) patients who have relapsed after chemotherapy or are chemotherapy resistant and have one or more sites of disease measuring more than 5 cm.
• The patients must have failed at least one chemotherapy regimen
• No anticancer treatment for three weeks prior to study initiation (six weeks if Rituximab, nitrosourea or Mitomycin C)
• Fully recovered from all toxicities associated with prior surgery, radiation, chemotherapy or immunotherapy
• An institutional review board- (IRB)-approved signed informed consent
• Age 19 years or older
• Expected survival of at least 6 months
• Prestudy Performance Status of 0, 1 or 2 according to the World Health Organization (WHO)
• Absolute neutrophil count (ANC) of at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hct > 30%
• Hgb > 9.0 gm
• Bilirubin ≤ 2.0
• Creatinine ≤ 2.0
• Bone marrow involvement with lymphoma less than 25% (bilateral bone marrow) within 6 weeks of enrollment
• Acceptable birth control method for men and women

Exclusion Criteria

• Disease progression within 3 months of last chemotherapy
• Prior myeloablative therapies with bone marrow transplantation or peripheral stem cell rescue
• Platelet count less than 100,000/mm³
• Hypocellular bone marrow (≤ 15% cellularity)
• Marked reduction in bone marrow precursors of one or more cell lines
• History of failed stem cell collection
• Prior treatment with fludarabine
• Prior radioimmunotherapy
• Presence of central nervous system (CNS) lymphoma
• HIV or AIDS-related lymphoma
• Evidence of myelodysplasia on bone marrow biopsy
• Abnormal bone marrow cytogenetics
• Patients who have received prior external beam radiation therapy to more than 25% of active bone marrow
• Patients who have received filgrastim
• Sargramostim therapy within 3 weeks prior to treatment
• Presence of human anti-mouse antibody (HAMA) reactivity in patients with prior exposure to murine antibodies or proteins
• Serious nonmalignant disease or infection, which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives
• Another primary malignancy (other than squamous cell and basal cell cancer of the skin, in situ carcinoma of the cervix, or treated prostate cancer with stable prostate-specific antigen, PSA) for which the patients has not been disease free for at least 3 years
• Major surgery, other than diagnostic surgery within 4 weeks
• Pleural effusion
• Pregnant
• Lactating

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Susan Knox

Associate Professor of Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan J Knox

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

97437

Identifier Type: OTHER

Identifier Source: secondary_id

LYMNHL0046

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-07479

Identifier Type: -

Identifier Source: org_study_id