Clinical trial NCT00070447: Rituximab, Prednisone, Cyclophosphamide, Doxorubicin, Vincristine, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Previously Untreated Mantle Cell Lymphoma
Official title: Phase II Study of Rituximab (NSC 687451) + CHOP Followed by 90Y-Ibritumomab Tiuxetan (NSC 710085) in Patients With Previously Untreated Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-10-07
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: 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. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab and combination chemotherapy together with yttrium Y 90 ibritumomab tiuxetan works in treating patients with previously untreated mantle cell lymphoma.

Detailed description: OBJECTIVES:

* Determine the time to treatment failure in patients with previously untreated mantle cell lymphoma treated with rituximab and CHOP chemotherapy comprising prednisone, cyclophosphamide, doxorubicin, and vincristine followed by yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8; yttrium Y 90 Zevalin®).
* Determine the response rate in patients at the completion of rituximab and CHOP and the incremental response rate after IDEC-Y2B8.
* Determine the toxicity of this regimen in these patients.
* Correlate serum rituximab levels with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

* CHOP chemotherapy and rituximab: Patients receive cyclophosphamide IV, doxorubicin IV, vincristine IV, and rituximab IV on day 1 and oral prednisone on days 1-5 (R + CHOP). Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients who have responding or stable disease proceed to radioimmunotherapy.

* Radioimmunotherapy: Within 4-7 weeks after the completion of R + CHOP chemotherapy, patients receive rituximab IV and an imaging dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo whole body gamma imaging scans during the first day (2-24 hours) and the second or third day (48-72 hours) after injection. In the absence of altered biodistribution, patients receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8; yttrium Y 90 Zevalin®) IV over 10 minutes on day 8.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 57 patients will be accrued for this study within 2.8 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed mantle cell lymphoma with expression of bcl-1 and CD20

  * Stage II-IV disease
* Measurable or evaluable disease

  * Measurable disease defined as at least 1 bidimensionally measurable lesion at least 2 cm by imaging scan
  * A spleen at least 17 cm or having discrete filling defects by CT scan will constitute evaluable disease provided that no explanation other than lymphomatous involvement (e.g., portal hypertension or other liver disease) is likely
* No known CNS lymphoma

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 6 months

Hematopoietic

* WBC greater than 2,500/mm\^3\*
* Platelet count greater than 100,000/mm\^3\* NOTE: \*Unless due to disease in bone marrow

Hepatic

* Bilirubin less than 1.5 mg/dL (1.5-3.0 mg/dL if due to liver involvement by lymphoma)
* ALT and AST no greater than 2.5 times upper limit of normal (unless due to liver involvement by lymphoma)

Renal

* Creatinine less than 2.0 mg/dL
* Calcium no greater than 11.5 mg/dL

Cardiovascular

* LVEF greater than 45%

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 1 year after study participation
* HIV negative
* No other malignancy except treated carcinoma in situ of the cervix or squamous cell or basal cell skin cancer or any other surgically cured malignancy from which the patient has been disease-free for at least 3 years
* No other concurrent serious medical condition or active infection that would preclude ability to deliver standard prednisone, cyclophosphamide, doxorubicin, and vincristine (CHOP) chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior immunotherapy

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Prior corticosteroids allowed provided the course was no more than 2 weeks in duration

Radiotherapy

* No prior radiotherapy

Surgery

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: CCOP - Mayo Clinic Scottsdale Oncology Program
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: MBCCOP - Howard University Cancer Center
state: District of Columbia
city: Gainesville
country: United States
facility: Veterans Affairs Medical Center - Gainesville
state: Florida
city: Miami
country: United States
facility: Veterans Affairs Medical Center - Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Onawa
country: United States
facility: Burgess Health Center
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Boston
country: United States
facility: Cancer Center at Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: Veterans Affairs Medical Center - Omaha
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Papillion
country: United States
facility: Midlands Cancer Center at Midlands Community Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: MBCCOP-Our Lady of Mercy Cancer Center
state: New York
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: New York
country: United States
facility: Veterans Affairs Medical Center - New York
state: New York
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: MetroHealth's Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Tulsa
country: United States
facility: CCOP - Oklahoma
state: Oklahoma
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans Affairs Medical Center - Pittsburgh
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Lima
country: Peru
facility: Instituto de Enfermedades Neoplasicas
city: San Juan
country: Puerto Rico
facility: MBCCOP - San Juan
city: San Juan
country: Puerto Rico
facility: Veterans Affairs Medical Center - San Juan
city: San Juan
country: Puerto Rico
facility: San Juan City Hospital
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospital
Study officials:
affiliation: Fox Chase Cancer Center
name: Mitchell R. Smith, MD, PhD
role: STUDY_CHAIR
affiliation: Robert H. Lurie Cancer Center
name: Leo I. Gordon, MD
References:
citation: Smith MR, Zhang L, Gordon LI, et al.: Phase II study of R-CHOP followed by 90Y-ibritumomab tiuxetan in untreated mantle cell lymphoma: Eastern Cooperative Oncology Group study E1499. [Abstract] Blood 110 (11): A-389, 2007.
citation: Smith MR, Chen H, Gordon L, et al.: Phase II study of rituximab + CHOP followed by 90Y-ibritumomab tiuxetan in patients with previously untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group Study (E1499). [Abstract] J Clin Oncol 24 (Suppl 18): A-7503, 422s, 2006.