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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070447

Purpose

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.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Rituximab Ibritumomab tiuxetan Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

November 2003

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070447

Show 87 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Mitchell R. Smith, MD, PhD	Fox Chase Cancer Center
Investigator:	Leo I. Gordon, MD	Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

ClinicalTrials.gov Identifier:	NCT00070447 History of Changes
Other Study ID Numbers:	CDR0000334470, ECOG-E1499
Study First Received:	October 3, 2003
Last Updated:	February 6, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on February 09, 2012