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

• ClinicalTrials.gov Identifier: NCT00490490
• Recruitment Status: Terminated
• First Posted: June 22, 2007
• Results First Posted: March 29, 2017
• Last Update Posted: March 29, 2017
• Sponsor: Stanford University
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Susan Knox, Stanford University

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Lymphoma, Non-Hodgkin	Drug: Bexxar (tositumomab); Procedure: External beam radiotherapy (XRT); Drug: Potassium Iodide (KI)	Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy for Patients With Relapsed, Bulky Non-Hodgkin's Lymphoma
• Study Start Date: January 2007
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: July 2013

Arms and Interventions

Arm

Intervention/treatment

Experimental: Tositumomab + XRT + KI; Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)

Drug: 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.; Other Name: 131-iodine tositumomab; Procedure: 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.; Other Name: Radiotherapy (RT); Drug: 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; Other Names: Saturated Solution Potassium Iodide (SSKI); Lugol's solution; Potassium iodide tablets

Outcome Measures

Primary Outcome Measures :

1. Complete Response (CR) Rate [ Time Frame: 12 weeks ]

   Participants assessed for by the following Complete Response (CR) criteria

   CR or Functional CR

   • No evidence of disease and symptoms
   • Any macroscopic nodules detected in any organs no longer present.
   • Any palpable lymph node is normal and greatest diameter is < 1.0 cm.
   • The enlarged organs decreased in size and not palpable
   • The bone marrow biopsy and aspirate are negative for disease
   • Negative for disease by PET-scan (functional CR)

   CR Unconfirmed (CRu) criteria

   • No evidence of disease and symptoms
   • Any lymph node mass > 1.0 cm^2 diameter has regressed is size by more than 75%.
   • No macroscopic nodules in any organs
   • Any palpable lymph node is normal and greatest diameter is < 1.0 cm.
   • The bone marrow biopsy and aspirate are negative for disease
   • The bone marrow biopsy may have increased number or size of lymphoid aggregates without cytologic or architectural atypia

Secondary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 12 weeks ]

   ORR is assessed as the sum of the overall rates of

   • CR confirmed by positron emission tomography (PET)
   • CR not confirmed by PET, and
   • Partial response (PR) negative for progression by PET
2. Time-to-Progression (TTP) [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

GlaxoSmithKline

Investigators

• Principal Investigator: Susan J Knox; Stanford University

More Information

• Responsible Party: Susan Knox, Associate Professor of Radiation Oncology, Stanford University
• ClinicalTrials.gov Identifier: NCT00490490
• Other Study ID Numbers: IRB-07479; 97437 ( Other Identifier: Stanford University Alternate IRB Approval Number ); LYMNHL0046 ( Other Identifier: OnCore )
• First Posted: June 22, 2007
• Results First Posted: March 29, 2017
• Last Update Posted: March 29, 2017
• Last Verified: February 2017

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Iodine; Lugol's solution; Pharmaceutical Solutions; Anti-Infective Agents, Local; Anti-Infective Agents; Trace Elements; Micronutrients; Physiological Effects of Drugs; Hemostatics; Coagulants