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Completed

NCT Number: NCT00107380

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

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.

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Key information

Conditions

Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year–120 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Alaska Regional Hospital Cancer Center, Anchorage, Alaska, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Rituximab

Biological

Cyclophosphamide

Drug

Doxorubicin hydrochloride

Drug

Prednisone

Drug

vincristine sulfate

Drug

tositumomab and iodine I 131 tositumomab

Radiation

Primary outcomes

  1. Progression-free Survival (PFS) at 2 Years

    Time frame: 0-2 years

    Clinical responses were evaluated according to International Workshop NHL criteria (Cheson et al, 1999). Progression disease was defined as if a (CR, CRU) was not achieved at a previous assessment, a 50% increase in the SPD of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Appearance of a new lesion/site. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Death due to disease without prior documentation of progression. PFS is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.

  2. Response Rate (Complete, Complete Unconfirmed, and Partial)

    Time frame: 6 months

    Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

Secondary outcomes

  1. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

    Time frame: 6 months (assessed at the end of each cycle of chemotherapy for 8 cycles (1 cycle= 21 days), at restaging, and at the end of each radiolabeled antibody treatment)

    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Sponsors and collaborators

Lead sponsor

SWOG Cancer Research Network

Network

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2013
Study completion
2015
First posted
Apr 6, 2005
Registry last updated
Mar 7, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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