Rituximab, Prednisone, Cyclophosphamide, Doxorubicin, Vincristine, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Previously Untreated Mantle Cell Lymphoma

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070447
• Other study ID #: CDR0000334470
• Secondary ID: ECOG-E1499
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2003
• Last updated: January 27, 2014
• Start date: November 2003
• Est. completion date: June 2006

Study information

• Verified date: October 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Biological:
• rituximab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• prednisone

• vincristine sulfate

Radiation:
• yttrium Y 90 ibritumomab tiuxetan

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales
Peru	Instituto de Enfermedades Neoplasicas	Lima
Puerto Rico	MBCCOP - San Juan	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	Veterans Affairs Medical Center - San Juan	San Juan
South Africa	Pretoria Academic Hospital	Pretoria
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Cancer Center at Tufts - New England Medical Center	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York
United States	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	MetroHealth's Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Central Illinois	Decatur	Illinois
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Veterans Affairs Medical Center - Gainesville	Gainesville	Florida
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Veterans Affairs Medical Center - Miami	Miami	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Veterans Affairs Medical Center - New York	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Veterans Affairs Medical Center - Omaha	Omaha	Nebraska
United States	Burgess Health Center	Onawa	Iowa
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Midlands Cancer Center at Midlands Community Hospital	Papillion	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Veterans Affairs Medical Center - Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Peru,  Puerto Rico,  South Africa, 

References & Publications (2)

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

Smith MR, Li H, Gordon L, Gascoyne RD, Paietta E, Forero-Torres A, Kahl BS, Advani R, Hong F, Horning SJ. Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiu — View Citation