S0313 Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Radiation Therapy Followed By Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: vincristine sulfate

Radiation: radiation therapy

Drug: Cyclophosphamide

Drug: prednisone

Biological: Indium-111 ibritumomab tiuxetan

Biological: rituximab

Drug: doxorubicin hydrochloride

Biological: Yttrium-90 ibritumomab tiuxetan

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00070018

CDR0000329864

U10CA032102 (U.S. NIH Grant/Contract)

S0313 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Monoclonal antibodies, such as rituximab and yttrium Y 90 ibritumomab tiuxetan, can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining chemotherapy with radiation therapy and monoclonal antibody therapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy and monoclonal antibody therapy works in treating patients with stage I or stage II non-Hodgkin's lymphoma.

Full description

OBJECTIVES:

Determine the 2-year progression-free survival of patients with aggressive high-risk stage I or IE or non-bulky stage II or IIE CD20-positive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone and radiotherapy followed by rituximab and yttrium Y 90 ibritumomab tiuxetan.
Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Chemotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 1-2 hours, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Radiotherapy: Beginning 3 weeks after the completion of CHOP chemotherapy, patients undergo radiotherapy once daily 5 days a week for 4-5 weeks.
Monoclonal antibody therapy: Beginning 3-6 weeks after the completion of radiotherapy, patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo whole body imaging. If ibritumomab tiuxetan biodistribution is acceptable, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, OR 9.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 15 months.

Enrollment

46 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:
- Diffuse large B-cell
- Mantle cell
- High-grade B-cell, Burkitt's, or Burkitt-like
- Anaplastic large cell (B-cell phenotype only)
Stage I, IE, or non-bulky* stage II or IIE disease by Ann Arbor classification
- Patients who have bulky stage II or IIE disease are ineligible even if, after resection, the measurements are less than 10.0 cm NOTE: *Non-bulky disease defined as any tumor measuring less than 10.0 cm or occupying less than 1/3 of the chest diameter
CD20-expressing disease by flow cytometry or immunoperoxidase staining
Aggressive lymphomas must have at least 1 of the following adverse prognostic factors:
- Non-bulky stage II or IIE disease
- At least 60 years of age
- Zubrod performance status of 2
- Lactic dehydrogenase greater than upper limit of normal
All disease must be encompassable in a single radiation port (including any site of resected disease) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

Over 18

Performance status

Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No medical contraindication to study chemotherapy, rituximab, or ibritumomab tiuxetan
No known AIDS syndrome or HIV-associated complex

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior monoclonal antibody therapy

Chemotherapy

No prior chemotherapy for lymphoma

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics
No prior radiotherapy for lymphoma
No concurrent intensity-modulated radiotherapy
Planned involved-field radiotherapy must not encompass more than 25% of active bone marrow space

Surgery

See Disease Characteristics

Other

Concurrent participation in SWOG-8947 or SWOG-8819 allowed

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

46 participants in 1 patient group

CHOP + RT + Zevalin

Experimental group

Description:

Patients first receive 3 cycles (21 days each) of CHOP, consisting of: cyclophosphamide 750 mg/m\^2 on day 1, doxorubicin 50 mg/m\^2 on day 1, vincristine 1.4 mg/m\^2 on day 1, and prednisone 100 mg on days 1-5. Patients receive 4000-5000 cGy of radiation therapy in 25 fractions, starting 3 weeks after completion of CHOP. 3-6 weeks after completing RT, patients receive Zevalin, which consists of: rituximab 250 mg/m\^2 on days 1 and 7, 8 or 9; In-111 ibritumomab tiuxetan 5 mCi within 4 hours after rituximab on day 1; and Y-90 ibritumomab tiuxetan 0.4 mCi/kg within 4 hours after rituximab on day 7, 8 or 9.

Treatment: