S0433 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Treating Older Patients With Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma

SWOG Cancer Research Network

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Radiation: tositumomab and iodine I 131 tositumomab; Biological: rituximab; Drug: vincristine sulfate; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00107380

S0433 (Other Identifier)

CDR0000415955

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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 B-cell lymphoma 2 (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.

Enrollment: 86 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 cluster of differentiation antigen 20 (CD20) antigen-positive disease

• Bidimensionally measurable disease

• Less than 20,000/mcL circulating lymphoid cells on white blood cell (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 central nervous system (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 multiple gated acquisition scan (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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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86 participants in 1 patient group

R-CHOP x 8 with I-131 Tositumomab

Experimental group

Description:

Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170 Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177

Treatment:

Radiation: tositumomab and iodine I 131 tositumomab

Drug: vincristine sulfate

Biological: rituximab

Drug: prednisone

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride