Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Treating Older Patients With Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00107380

Purpose

RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving a radiolabeled monoclonal antibody together with rituximab and combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving iodine I 131 tositumomab together with rituximab and combination chemotherapy works in treating older patients with stage II, stage III, or stage IV B-cell non-Hodgkin's lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Radiation: tositumomab and iodine I 131 tositumomab	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Iodine-131-Labeled Monoclonal Anti-B1 Antibody (I-131 Tositumomab) in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients ≥ Age 60 With Advanced Stage Diffuse Large B-Cell NHL: A Phase II Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Cadexomer iodine Rituximab Tositumomab Vincristine sulfate Iodine Sodium iodide I 131

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival at 2 years [ Designated as safety issue: No ]
Response rate after study completion [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival of subgroup at 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	November 2005
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the 2-year progression-free survival of older patients with previously untreated bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma treated with iodine I 131 tositumomab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
Determine the response rate (partial response, complete unconfirmed response, and complete response) in patients treated with this regimen.
Determine the 2-year progression-free survival and response rate (partial response, complete unconfirmed response, and complete response) in BCL-2 positive patients treated with this regimen.

OUTLINE: This is a multicenter study.

Rituximab and chemotherapy: Patients receive R-CHOP comprising rituximab IV over 6 hours; cyclophosphamide IV over 15-45 minutes; doxorubicin IV over 5-20 minutes; and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a restaging evaluation. Patients without progressive disease receive CHOP chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone as outlined above. Treatment with CHOP chemotherapy repeats every 21 days for 2 courses.
Radiolabeled monoclonal antibody therapy: Approximately 4-8 weeks after completion of chemotherapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo gamma scans over a 1-week period in order to determine the correct treatment dose of iodine I 131 tositumomab. No more than 2 weeks after administration of the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a treatment dose of iodine I 131 tositumomab IV over 20 minutes.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 15 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of diffuse large B-cell non-Hodgkin's lymphoma, meeting 1 of the following stage criteria:
- Bulky stage II disease
- Stage III disease
- Stage IV disease
Confirmed CD20 antigen-positive disease
Bidimensionally measurable disease
Less than 20,000/mcL circulating lymphoid cells on WBC differential count
Adequate sections AND a paraffin block OR ≥ 10 unstained sections from the original diagnostic specimen available
- Needle aspiration or cytology are not considered adequate
No clinical evidence of CNS involvement by lymphoma
No prior diagnosis of indolent lymphoma
- No histologic transformation

PATIENT CHARACTERISTICS:

Performance status

Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Not specified

Renal

Not specified

Cardiovascular

Ejection fraction ≥ 45% by MUGA OR
No significant abnormalities by echocardiogram

Pulmonary

No requirement for continuous supplemental oxygen

Other

Fertile patients must use effective contraception during and for 6 months after completion of study treatment
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, stage I or II cancer in complete remission, or carcinoma in situ of the cervix
No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior antibody therapy for lymphoma

Chemotherapy

No prior chemotherapy for lymphoma

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy for lymphoma

Surgery

No prior solid organ transplantation

Other

Concurrent enrollment on protocol SWOG-8947 (lymphoma serum repository) or protocol SWOG-8819 (lymphoma tissue repository) is encouraged

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107380

Show 78 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Jonathan W. Friedberg, MD	James P. Wilmot Cancer Center
Investigator:	Richard I. Fisher, MD	James P. Wilmot Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Southwest Oncology Group - Group Chair's Office ( Laurence H. Baker )
Study ID Numbers:	CDR0000415955, SWOG-S0433
Study First Received:	April 5, 2005
Last Updated:	February 4, 2010
ClinicalTrials.gov Identifier:	NCT00107380 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Iodine-131 anti-B1 antibody
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Antibodies, Monoclonal
Therapeutic Uses
Iodine

Micronutrients
Lymphoma
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Growth Substances
Mitosis Modulators
Vincristine
Trace Elements
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 09, 2010