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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00770224
• Other study ID #: CDR0000615104
• Secondary ID: S0801U10CA032102
• Status: Completed
• Phase: Phase 2
• Start date: April 2009
• Est. completion date: August 2019

Study information

• Verified date: August 2019
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: August 2019
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• rituximab

• tositumomab

Drug:
• cyclophosphamide

• doxorubicin

• prednisone

• vincristine

Radiation:
• tositumomab

Locations

Country	Name	City	State
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	AnMed Cancer Center	Anderson	South Carolina
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Falck Cancer Center at Arnot Ogden Medical Center	Elmira	New York
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	U.T. Medical Center Cancer Institute	Knoxville	Tennessee
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Providence Cancer Center at Providence Hospital	Mobile	Alabama
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Metro Health Hospital	Wyoming	Michigan
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With 3-year Progression-free Survival (PFS)	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.	0-3 years
Secondary	5-year Progression-free Survival	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.	0-5 years
Secondary	5-year Overall Survival	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.	0-5 years
Secondary	Response Rate	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. Positron emission tomography (PET) must be negative if no pre-treatment 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 pre-treatment PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.	up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression
Secondary	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	up to 5 years (1 year induction + 4 years maintenance therapy) or time of disease progression.