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S0801 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00770224
First Posted: October 9, 2008
Last Update Posted: July 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
  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 the side effects of giving iodine I 131 tositumomab together with rituximab and combination chemotherapy and to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma Biological: rituximab Biological: tositumomab Drug: cyclophosphamide Drug: doxorubicin Drug: prednisone Drug: vincristine Radiation: tositumomab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Iodine-131-Labeled Tositumomab in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients With Advanced Stage Follicular Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 3-year progression-free survival (PFS) [ Time Frame: 0-3 years ]
    Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node > 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is > 1.5 cm, or if the both the long and short axes are > 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.


Secondary Outcome Measures:
  • 5-year Progression-free Survival [ Time Frame: 0-5 years ]
    Measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is ≥ 50% increase in the sum of products of greatest diameters (SPD) of target measurable nodal lesions over the smallest sum observed (over baseline if no decrease during therapy), or ≥ 50% increase in the greatest transverse diameter (GTD) of any node > 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions (e.g., splenic or hepatic nodules) over the smallest sum observed. Appearance of any new bone marrow involvement; appearance of a new lesion/site; lymph nodes with the long axis is > 1.5 cm, or if the both the long and short axes are > 1 cm; in patients with no pretreatment PET scan or when the PET scan was positive before therapy, lesions should be PET positive; or death due to disease without prior documentation of progression.

  • 5-year overall survival [ Time Frame: 0-5 years ]
    Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.

  • Response rate [ Time Frame: up to 1 year while on treatment, or up to maximum of 7 years on protocol, or time of disease progression ]
    Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of the following. PET must be negative if no pretreatment PET scan or when the PET was positive before therapy. If the PET scan was negative before therapy, all nodal masses must have regressed. no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. PR is ≥ 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. In patients with no pretreatment PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.

  • Safety profile as assessed by NCI CTCAE v4.0 [ Time Frame: up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression ]
    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.


Enrollment: 87
Study Start Date: April 2009
Estimated Study Completion Date: December 2017
Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-CHOP, tositumomab and rituximab

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

Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody.

Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration.

Biological: rituximab Biological: tositumomab Drug: cyclophosphamide Drug: doxorubicin Drug: prednisone Drug: vincristine Radiation: tositumomab
Other Name: iodine I 131 tositumomab

Detailed Description:

OBJECTIVES:

  • To evaluate the response rate in patients with previously untreated stage II-IV follicular non-Hodgkin lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in combination with iodine I 131 tositumomab.
  • To evaluate the toxicity of this regimen in these patients.
  • To estimate the 3-year progression-free survival rate in patients treated with this regimen.
  • To estimate the 5-year progression-free and overall survival rate in patients treated with this regimen.
  • To assess the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive R-CHOP* comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease then proceed to consolidation therapy.

NOTE: *Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6.

  • Consolidation therapy: Within 12 weeks after completion of induction therapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo whole body gamma camera scans over a 1-week period to determine the rate of total body clearance of radioactivity and the therapeutic dose of iodine I 131 tositumomab. Within 7-14 days after the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a therapeutic dose of iodine I 131 tositumomab IV over 20 minutes. Patients with at least stable disease then proceed to maintenance therapy.
  • Maintenance therapy: Beginning approximately 1 year after study entry and no more than 28 days after restaging, patients receive rituximab IV every 3 months for up to 4 years (16 courses) in the absence of disease progression or unacceptable toxicity.

After completion of maintenance therapy, patients are followed annually for up to 7 years. Patients who do not complete maintenance therapy are followed every 6 months for 2 years and then annually for up to 7 years.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* grade 1, 2, or 3 follicular B-cell non-Hodgkin lymphoma meeting the following criteria:

    • Bulky stage II or stage III or IV disease
    • Diffuse large cell component must be < 25% of the biopsy
    • Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease NOTE: *Needle aspiration or cytology are not considered adequate for pathology review
  • Patient must have unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days

    • Positive biopsy performed > 42 days but < 6 months allowed
  • Previously untreated disease
  • Bidimensionally measurable disease
  • No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Cardiac ejection fraction ≥ 45% by multigated acquisition scan (MUGA) or ECHO
  • No significant cardiac abnormalities
  • No known HIV positivity
  • No requirement for continuous supplemental oxygen therapy
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 12 months after completion of maintenance therapy

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
  • No prior solid organ transplantation
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00770224


  Hide Study Locations
Locations
United States, Alabama
Providence Cancer Center at Providence Hospital
Mobile, Alabama, United States, 36608
United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
United States, Illinois
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
Cancer Care Center of Decatur
Decatur, Illinois, United States, 62526
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Crossroads Cancer Center
Effingham, Illinois, United States, 62401
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Good Samaritan Regional Health Center
Mount Vernon, Illinois, United States, 62864
Regional Cancer Center at Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services
Richmond, Indiana, United States, 47374
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, United States, 66701
Cancer Center of Kansas-Independence
Independence, Kansas, United States, 67301
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67401
Tammy Walker Cancer Center at Salina Regional Health Center
Salina, Kansas, United States, 67401
Cotton-O'Neil Cancer Center
Topeka, Kansas, United States, 66606
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
CCOP - Wichita
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Wesley Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
United States, Michigan
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, United States, 49017
Mecosta County Medical Center
Big Rapids, Michigan, United States, 49307
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, United States, 49503
Mercy General Health Partners
Muskegon, Michigan, United States, 49443
Munson Medical Center
Traverse City, Michigan, United States, 49684
Metro Health Hospital
Wyoming, Michigan, United States, 49519
United States, Mississippi
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States, 39216
United States, Missouri
Saint Francis Medical Center
Cape Girardeau, Missouri, United States, 63703
Midwest Hematology Oncology Group, Incorporated
Saint Louis, Missouri, United States, 63109
CCOP - St. Louis-Cape Girardeau
Saint Louis, Missouri, United States, 63141
David C. Pratt Cancer Center at St. John's Mercy
Saint Louis, Missouri, United States, 63141
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
St. Vincent Healthcare Cancer Care Services
Billings, Montana, United States, 59101
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59102
Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
St. James Healthcare Cancer Care
Butte, Montana, United States, 59701
Great Falls Clinic - Main Facility
Great Falls, Montana, United States, 59405
Sletten Cancer Institute at Benefis Healthcare
Great Falls, Montana, United States, 59405
Northern Montana Hospital
Havre, Montana, United States, 59501
St. Peter's Hospital
Helena, Montana, United States, 59601
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Kalispell Medical Oncology at KRMC
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
United States, New York
Falck Cancer Center at Arnot Ogden Medical Center
Elmira, New York, United States, 14905
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Rutherford Hospital
Rutherfordton, North Carolina, United States, 28139
United States, Ohio
Mary Rutan Hospital
Bellefontaine, Ohio, United States, 43311
Adena Regional Medical Center
Chillicothe, Ohio, United States, 45601
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
CCOP - Columbus
Columbus, Ohio, United States, 43215
Grant Medical Center Cancer Care
Columbus, Ohio, United States, 43215
Mount Carmel Health - West Hospital
Columbus, Ohio, United States, 43222
Doctors Hospital at Ohio Health
Columbus, Ohio, United States, 43228
Grandview Hospital
Dayton, Ohio, United States, 45405
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
CCOP - Dayton
Dayton, Ohio, United States, 45420
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Wayne Hospital
Greenville, Ohio, United States, 45331
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
Knox Community Hospital
Mount Vernon, Ohio, United States, 43050
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, United States, 43055
Community Hospital of Springfield and Clark County
Springfield, Ohio, United States, 45505
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Mount Carmel St. Ann's Cancer Center
Westerville, Ohio, United States, 43081
Clinton Memorial Hospital
Wilmington, Ohio, United States, 45177
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
Genesis - Good Samaritan Hospital
Zanesville, Ohio, United States, 43701
United States, South Carolina
AnMed Cancer Center
Anderson, South Carolina, United States, 29621
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
U.T. Medical Center Cancer Institute
Knoxville, Tennessee, United States, 37920-6999
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
St. Joseph Cancer Center
Bellingham, Washington, United States, 98225
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Columbia Basin Hematology
Kennewick, Washington, United States, 99336
Skagit Valley Hospital Cancer Care Center
Mount Vernon, Washington, United States, 98273
Harrison Poulsbo Hematology and Onocology
Poulsbo, Washington, United States, 98370
Harborview Medical Center
Seattle, Washington, United States, 98104
Minor and James Medical, PLLC
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Group Health Central Hospital
Seattle, Washington, United States, 98112
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98122-4307
Polyclinic First Hill
Seattle, Washington, United States, 98122
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Evergreen Hematology and Oncology, PS
Spokane, Washington, United States, 99218
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
United States, Wyoming
Rocky Mountain Oncology
Casper, Wyoming, United States, 82609
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Jonathan W. Friedberg, MD James P. Wilmot Cancer Center
Study Chair: Oliver W. Press, MD, PhD Fred Hutchinson Cancer Research Center
Study Chair: Lisa Rimsza, MD University of Arizona
  More Information

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00770224     History of Changes
Other Study ID Numbers: CDR0000615104
S0801 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted: October 8, 2008
First Posted: October 9, 2008
Last Update Posted: July 18, 2017
Last Verified: July 2017

Keywords provided by Southwest Oncology Group:
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Iodine-131 anti-B1 antibody
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal
Iodine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors