MedPath

Rituximab and Denileukin Diftitox in Treating Patients With Previously Untreated Stage III or Stage IV Follicular B-Cell Non-Hodgkin's Lymphoma

Phase 2
Completed
Conditions
Lymphoma
Interventions
Biological: denileukin diftitox
Biological: rituximab
Registration Number
NCT00460109
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

RATIONALE: 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. Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to cancer cells. Giving rituximab together with denileukin diftitox may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with denileukin diftitox works in treating patients with previously untreated stage III or stage IV follicular B-cell non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

Primary

* Determine the response rate (complete response \[CR\], unconfirmed CR, and partial response) in patients with previously untreated stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with rituximab and denileukin diftitox.

* Assess the overall survival, time-to-progression, duration of response, and time-to-new therapy in patients treated with this regimen.

Secondary

* Determine whether this regimen depletes or inhibits the function of regulatory T cells in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline; on day 1 of courses 2-4; and 1 and 4 months after completion of study treatment for research studies. Research studies include analysis of peripheral blood lymphocyte subsets expressing CD3, CD4, CD8, CD19, CD25, and CD26 by flow cytometry; quantitation of CD4+, CD25+ regulatory T cells by flow cytometry; tumor-specific γ-interferon-secreting T cells by enzyme-linked immunospot assay; tumor-specific cytotoxic T-lymphocyte activity; and immune activation by enzyme-linked immunosorbent assay.

After completion of study treatment, patients are followed periodically for up to 5 years after registration.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
rituximab + denileukin diftitoxdenileukin diftitoxPatients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
rituximab + denileukin diftitoxrituximabPatients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response)Up to 5 years

A confirmed tumor response is defined to be either a CR, CRu or PR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.

Secondary Outcome Measures
NameTimeMethod
Duration of ResponseUp to 5 years

Duration of response (DOR) is defined as the time from the date at which the patient's objective status is first noted to be either a CR, CRu or PR to the earliest date of progression. The distribution of DOR will be estimated using Kaplan-Meier methods. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.

Time to Subsequent TherapyUp to 5 years

Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.

Time to Disease ProgressionUp to 5 years

Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier. Progression is defined using the response criteria for non-Hodgkin's lymphoma, as at least a 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or non-responders, or appearance of any new lesion during or at the end of therapy.

Survival TimeUp to 5 years

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Trial Locations

Locations (164)

Rush-Copley Cancer Care Center

🇺🇸

Aurora, Illinois, United States

Boulder Community Hospital

🇺🇸

Boulder, Colorado, United States

Mayo Clinic Scottsdale

🇺🇸

Scottsdale, Arizona, United States

St. Anthony's Memorial Hospital

🇺🇸

Effingham, Illinois, United States

CCOP - Northern Indiana CR Consortium

🇺🇸

South Bend, Indiana, United States

CCOP - Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Mercy Medical Center - Sioux City

🇺🇸

Sioux City, Iowa, United States

Howard Community Hospital

🇺🇸

Kokomo, Indiana, United States

Penrose Cancer Center at Penrose Hospital

🇺🇸

Colorado Springs, Colorado, United States

Michiana Hematology-Oncology, PC - South Bend

🇺🇸

South Bend, Indiana, United States

Cancer Center of Kansas, PA - Parsons

🇺🇸

Parsons, Kansas, United States

Carle Cancer Center at Carle Foundation Hospital

🇺🇸

Urbana, Illinois, United States

Miller - Dwan Medical Center

🇺🇸

Duluth, Minnesota, United States

Center for Cancer Therapy at LaPorte Hospital and Health Services

🇺🇸

La Porte, Indiana, United States

Elkhart General Hospital

🇺🇸

Elkhart, Indiana, United States

Cancer Center of Kansas, PA - Dodge City

🇺🇸

Dodge City, Kansas, United States

Minnesota Oncology Hematology, PA - Woodbury

🇺🇸

Woodbury, Minnesota, United States

Southwest Medical Center

🇺🇸

Liberal, Kansas, United States

Mid Dakota Clinic, PC

🇺🇸

Bismarck, North Dakota, United States

St. Francis Cancer Center at St. Francis Medical Center

🇺🇸

Shakopee, Minnesota, United States

Strecker Cancer Center at Marietta Memorial Hospital

🇺🇸

Marietta, Ohio, United States

Medcenter One Hospital Cancer Care Center

🇺🇸

Bismarck, North Dakota, United States

Cancer Center of Kansas, PA - Salina

🇺🇸

Salina, Kansas, United States

Cancer Center of Kansas, PA - Wichita

🇺🇸

Wichita, Kansas, United States

Memorial Hospital of South Bend

🇺🇸

South Bend, Indiana, United States

North Suburban Medical Center

🇺🇸

Thornton, Colorado, United States

Saint Anthony Memorial Health Centers

🇺🇸

Michigan City, Indiana, United States

Cancer Center of Kansas, PA - Kingman

🇺🇸

Kingman, Kansas, United States

Lawrence Memorial Hospital

🇺🇸

Lawrence, Kansas, United States

HealthEast Cancer Care at St. John's Hospital

🇺🇸

Maplewood, Minnesota, United States

Cancer Center of Kansas, PA - El Dorado

🇺🇸

El Dorado, Kansas, United States

Cancer Center of Kansas, PA - Newton

🇺🇸

Newton, Kansas, United States

MeritCare Bemidji

🇺🇸

Bemidji, Minnesota, United States

Cancer Center of Kansas - Fort Scott

🇺🇸

Fort Scott, Kansas, United States

CCOP - Wichita

🇺🇸

Wichita, Kansas, United States

Seton Cancer Institute at Saint Mary's - Saginaw

🇺🇸

Saginaw, Michigan, United States

Fairview Southdale Hospital

🇺🇸

Edina, Minnesota, United States

Cancer Center of Kansas, PA - Wellington

🇺🇸

Wellington, Kansas, United States

Fairfield Medical Center

🇺🇸

Lancaster, Ohio, United States

CCOP - Metro-Minnesota

🇺🇸

Saint Louis Park, Minnesota, United States

St. Luke's Regional Medical Center

🇺🇸

Sioux City, Iowa, United States

St. Alexius Medical Center Cancer Center

🇺🇸

Bismarck, North Dakota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

Altru Cancer Center at Altru Hospital

🇺🇸

Grand Forks, North Dakota, United States

Fairview Ridges Hospital

🇺🇸

Burnsville, Minnesota, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center

🇺🇸

Grosse Pointe Woods, Michigan, United States

Cancer Center of Kansas, PA - Medical Arts Tower

🇺🇸

Wichita, Kansas, United States

Foote Memorial Hospital

🇺🇸

Jackson, Michigan, United States

Minnesota Oncology Hematology, PA - Maplewood

🇺🇸

Maplewood, Minnesota, United States

MeritCare Broadway

🇺🇸

Fargo, North Dakota, United States

Hurley Medical Center

🇺🇸

Flint, Michigan, United States

Dickinson County Healthcare System

🇺🇸

Iron Mountain, Michigan, United States

Sparrow Regional Cancer Center

🇺🇸

Lansing, Michigan, United States

Community Medical Center

🇺🇸

Missoula, Montana, United States

Grant Medical Center Cancer Care

🇺🇸

Columbus, Ohio, United States

Duluth Clinic Cancer Center - Duluth

🇺🇸

Duluth, Minnesota, United States

Mercy and Unity Cancer Center at Unity Hospital

🇺🇸

Fridley, Minnesota, United States

CCOP - MeritCare Hospital

🇺🇸

Fargo, North Dakota, United States

Green Bay Oncology, Limited - Escanaba

🇺🇸

Escanaba, Michigan, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center

🇺🇸

Dearborn, Michigan, United States

St. Mary Mercy Hospital

🇺🇸

Livonia, Michigan, United States

Mercy Medical Center

🇺🇸

Springfield, Ohio, United States

Mercy Regional Cancer Center at Mercy Hospital

🇺🇸

Port Huron, Michigan, United States

Genesys Hurley Cancer Institute

🇺🇸

Flint, Michigan, United States

Adena Regional Medical Center

🇺🇸

Chillicothe, Ohio, United States

Green Bay Oncology, Limited - Oconto Falls

🇺🇸

Oconto Falls, Wisconsin, United States

Green Bay Oncology, Limited at St. Mary's Hospital

🇺🇸

Green Bay, Wisconsin, United States

Mary Rutan Hospital

🇺🇸

Bellefontaine, Ohio, United States

Grady Memorial Hospital

🇺🇸

Delaware, Ohio, United States

Mount Carmel Health - West Hospital

🇺🇸

Columbus, Ohio, United States

Medical X-Ray Center, PC

🇺🇸

Sioux Falls, South Dakota, United States

Mount Carmel St. Ann's Cancer Center

🇺🇸

Westerville, Ohio, United States

Providence Milwaukie Hospital

🇺🇸

Milwaukie, Oregon, United States

Welch Cancer Center at Sheridan Memorial Hospital

🇺🇸

Sheridan, Wyoming, United States

Franciscan Skemp Healthcare - La Crosse Campus

🇺🇸

La Crosse, Wisconsin, United States

Southwest Washington Medical Center Cancer Center

🇺🇸

Vancouver, Washington, United States

Holy Family Memorial Medical Center Cancer Care Center

🇺🇸

Manitowoc, Wisconsin, United States

Green Bay Oncology, Limited - Sturgeon Bay

🇺🇸

Sturgeon Bay, Wisconsin, United States

St. Vincent Hospital Regional Cancer Center

🇺🇸

Green Bay, Wisconsin, United States

Riverside Methodist Hospital Cancer Care

🇺🇸

Columbus, Ohio, United States

Rocky Mountain Oncology

🇺🇸

Casper, Wyoming, United States

St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

🇺🇸

Grand Junction, Colorado, United States

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

🇺🇸

Hartford, Connecticut, United States

St. Mary - Corwin Regional Medical Center

🇺🇸

Pueblo, Colorado, United States

Elkhart Clinic, LLC

🇺🇸

Elkhart, Indiana, United States

South Bend Clinic

🇺🇸

South Bend, Indiana, United States

Medical Oncology and Hematology Associates - West Des Moines

🇺🇸

Clive, Iowa, United States

Saint Joseph Regional Medical Center

🇺🇸

South Bend, Indiana, United States

Mercy Cancer Center at Mercy Medical Center - North Iowa

🇺🇸

Mason City, Iowa, United States

Siouxland Hematology-Oncology Associates, LLP

🇺🇸

Sioux City, Iowa, United States

Cancer Center of Kansas-Independence

🇺🇸

Independence, Kansas, United States

Cancer Center of Kansas, PA - Pratt

🇺🇸

Pratt, Kansas, United States

Via Christi Cancer Center at Via Christi Regional Medical Center

🇺🇸

Wichita, Kansas, United States

Lakeland Regional Cancer Care Center - St. Joseph

🇺🇸

St. Joseph, Michigan, United States

CCOP - Duluth

🇺🇸

Duluth, Minnesota, United States

Mercy and Unity Cancer Center at Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Fergus Falls Medical Group, PA

🇺🇸

Fergus Falls, Minnesota, United States

Hutchinson Area Health Care

🇺🇸

Hutchinson, Minnesota, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

Northern Montana Hospital

🇺🇸

Havre, Montana, United States

St. Vincent Healthcare Cancer Care Services

🇺🇸

Billings, Montana, United States

Great Falls Clinic - Main Facility

🇺🇸

Great Falls, Montana, United States

St. James Healthcare Cancer Care

🇺🇸

Butte, Montana, United States

Glacier Oncology, PLLC

🇺🇸

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

🇺🇸

Kalispell, Montana, United States

Bismarck Cancer Center

🇺🇸

Bismarck, North Dakota, United States

CCOP - Columbus

🇺🇸

Columbus, Ohio, United States

Licking Memorial Cancer Care Program at Licking Memorial Hospital

🇺🇸

Newark, Ohio, United States

Doctors Hospital at Ohio Health

🇺🇸

Columbus, Ohio, United States

Community Hospital of Springfield and Clark County

🇺🇸

Springfield, Ohio, United States

Genesis - Good Samaritan Hospital

🇺🇸

Zanesville, Ohio, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

Sanford Cancer Center at Sanford USD Medical Center

🇺🇸

Sioux Falls, South Dakota, United States

Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center

🇺🇸

Green Bay, Wisconsin, United States

St. Mary's Hospital Medical Center - Green Bay

🇺🇸

Green Bay, Wisconsin, United States

Bay Area Cancer Care Center at Bay Area Medical Center

🇺🇸

Marinette, Wisconsin, United States

Swedish Medical Center

🇺🇸

Englewood, Colorado, United States

Billings Clinic - Downtown

🇺🇸

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

🇺🇸

Billings, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

🇺🇸

Missoula, Montana, United States

CCOP - Montana Cancer Consortium

🇺🇸

Billings, Montana, United States

Northern Rockies Radiation Oncology Center

🇺🇸

Billings, Montana, United States

Sletten Cancer Institute at Benefis Healthcare

🇺🇸

Great Falls, Montana, United States

Bozeman Deaconess Cancer Center

🇺🇸

Bozeman, Montana, United States

St. Peter's Hospital

🇺🇸

Helena, Montana, United States

Guardian Oncology and Center for Wellness

🇺🇸

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

🇺🇸

Missoula, Montana, United States

Cancer Center of Kansas, PA - Chanute

🇺🇸

Chanute, Kansas, United States

Associates in Womens Health, PA - North Review

🇺🇸

Wichita, Kansas, United States

Cancer Center of Kansas, PA - Winfield

🇺🇸

Winfield, Kansas, United States

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

🇺🇸

Robbinsdale, Minnesota, United States

Hennepin County Medical Center - Minneapolis

🇺🇸

Minneapolis, Minnesota, United States

Regions Hospital Cancer Care Center

🇺🇸

St. Paul, Minnesota, United States

Park Nicollet Cancer Center

🇺🇸

Saint Louis Park, Minnesota, United States

North Colorado Medical Center

🇺🇸

Greeley, Colorado, United States

Exempla Lutheran Medical Center

🇺🇸

Wheat Ridge, Colorado, United States

Hope Cancer Care Center at Longmont United Hospital

🇺🇸

Longmont, Colorado, United States

McKee Medical Center

🇺🇸

Loveland, Colorado, United States

St. Joseph Mercy Oakland

🇺🇸

Pontiac, Michigan, United States

Lakeside Cancer Specialists, PLLC

🇺🇸

Saint Joseph, Michigan, United States

St. John Macomb Hospital

🇺🇸

Warren, Michigan, United States

Sky Ridge Medical Center

🇺🇸

Lone Tree, Colorado, United States

Aurora Presbyterian Hospital

🇺🇸

Aurora, Colorado, United States

St. Anthony Central Hospital

🇺🇸

Denver, Colorado, United States

Porter Adventist Hospital

🇺🇸

Denver, Colorado, United States

Presbyterian - St. Luke's Medical Center

🇺🇸

Denver, Colorado, United States

St. Joseph Hospital

🇺🇸

Denver, Colorado, United States

Rose Medical Center

🇺🇸

Denver, Colorado, United States

CCOP - Colorado Cancer Research Program

🇺🇸

Denver, Colorado, United States

Saint Joseph Mercy Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

CCOP - Michigan Cancer Research Consortium

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

Adventist Medical Center

🇺🇸

Portland, Oregon, United States

Providence Cancer Center at Providence Portland Medical Center

🇺🇸

Portland, Oregon, United States

CCOP - Columbia River Oncology Program

🇺🇸

Portland, Oregon, United States

Providence St. Vincent Medical Center

🇺🇸

Portland, Oregon, United States

Mercy Capitol Hospital

🇺🇸

Des Moines, Iowa, United States

CCOP - Iowa Oncology Research Association

🇺🇸

Des Moines, Iowa, United States

John Stoddard Cancer Center at Iowa Methodist Medical Center

🇺🇸

Des Moines, Iowa, United States

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

🇺🇸

Des Moines, Iowa, United States

Medical Oncology and Hematology Associates at Mercy Cancer Center

🇺🇸

Des Moines, Iowa, United States

Mercy Cancer Center at Mercy Medical Center - Des Moines

🇺🇸

Des Moines, Iowa, United States

John Stoddard Cancer Center at Iowa Lutheran Hospital

🇺🇸

Des Moines, Iowa, United States

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