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

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00490490
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 78
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Jan 1, 2007
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jul 1, 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 Names: 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 Names: 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 [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) [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) [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• GlaxoSmithKline

Investigators

• Principal Investigator: Susan J Knox, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Susan Knox, Associate Professor of Radiation Oncology, Stanford University
• ClinicalTrials.gov Identifier: NCT00490490
• Other Study ID Numbers: IRB-07479; 97437; LYMNHL0046
• First Posted: Jun 22, 2007
• Last Update Posted: Mar 29, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Iodine; Lugol's solution; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Tositumomab + XRT + KI
Arm/Group Description	Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Period Title: Completed Assessment for CR
STARTED	8
COMPLETED	8
NOT COMPLETED	0
Period Title: Completed Assessment for CR
STARTED	8
COMPLETED	5
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Tositumomab + XRT + KI
Arm/Group Description	Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 62.5%
>=65 years	3 37.5%
Sex: Female, Male (Count of Participants)
Female	2 25%
Male	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	7 87.5%
Unknown or Not Reported	1 12.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 87.5%
More than one race	0 0%
Unknown or Not Reported	1 12.5%
Histology (Count of Participants)
Follicular Lymphoma, Grade 1	2 25%
Follicular Lymphoma, Grade 2	2 25%
Follicular Lymphoma, Grade 3	2 25%
Marginal Zone B-Cell Lymphoma	2 25%

Outcome Measures

1. Primary Outcome

Title	Complete Response (CR) Rate
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tositumomab + XRT + KI
Arm/Group Description	Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Measure Participants	8
CR	37.5 468.8%
Partial response (PR) or stable disease (SD)	62.5 781.3%

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tositumomab + XRT + KI
Arm/Group Description	Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Measure Participants	8
All CR + PR	50 625%
Partial Response (PR)	12.5 156.3%
Stable Disease (SD)	50 625%
Progressive disease (PD)	0 0%

3. Secondary Outcome

Title	Time-to-Progression (TTP)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

One subject has not progressed (assessment not possible), and one subject has been lost to follow-up.

Arm/Group Title	Tositumomab + XRT + KI
Arm/Group Description	Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
Measure Participants	6
3 months	1 12.5%
6 months	1 12.5%
9 months	1 12.5%
18 months	2 25%
60 months	1 12.5%

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Tositumomab + XRT + KI
Arm/Group Description	Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI)
All Cause Mortality
	Tositumomab + XRT + KI
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tositumomab + XRT + KI
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anemia	3/8 (37.5%)	7
Thrombocytopenia	8/8 (100%)	8
Neutropenia	4/8 (50%)	10
Other (Not Including Serious) Adverse Events
	Tositumomab + XRT + KI
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anemia	8/8 (100%)	8
Neutropenia	7/8 (87.5%)	7
Thrombocytoperia	8/8 (100%)	8
Leukocytopenia	8/8 (100%)	8
Cardiac disorders
Chest Pain	1/8 (12.5%)	1
Ear and labyrinth disorders
Equilibrium abnormal	1/8 (12.5%)	1
Gastrointestinal disorders
Nausea	5/8 (62.5%)	5
Diarrhea	1/8 (12.5%)	1
Stomach Pain	1/8 (12.5%)	1
General disorders
Fatigue	5/8 (62.5%)	14
Chills	1/8 (12.5%)	1
Body aches	2/8 (25%)	2
Infections and infestations
Infection, Finger	1/8 (12.5%)	1
Mouth Sores	1/8 (12.5%)	3
Swollem Lymph Nodes	1/8 (12.5%)	2
Lung Infection	1/8 (12.5%)	1
Metabolism and nutrition disorders
Indigestion	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Back Pain	3/8 (37.5%)	3
Body Aches	1/8 (12.5%)	1
Bone Pain	1/8 (12.5%)	1
Back spasms	1/8 (12.5%)	1
Pain in Hip/Leg	1/8 (12.5%)	1
Pain at biopsy site (lower back)	1/8 (12.5%)	1
R Armpit Pain	1/8 (12.5%)	1
Pain, side	1/8 (12.5%)	1
Nervous system disorders
Headaches	8/8 (100%)	8
Dizziness	1/8 (12.5%)	1
Neuropathy	2/8 (25%)	2
Tremor	1/8 (12.5%)	1
Headache, Chronic	1/8 (12.5%)	1
Headaches	5/8 (62.5%)	15
Dizziness	1/8 (12.5%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/8 (25%)	2
Sore Throat	2/8 (25%)	2
Skin and subcutaneous tissue disorders
Burning sensation	1/8 (12.5%)	1
Itchiness, hands and feet	1/8 (12.5%)	1
Skin Rash	2/8 (25%)	2
Itchiness, nose and mouth	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.