Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00058422

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 use different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan in treating older patients who have B-cell lymphoma that has not been previously treated.

Condition	Intervention	Phase
Lymphoma	Drug: cyclophosphamide Drug: darbepoetin alfa Drug: doxorubicin hydrochloride Drug: filgrastim Drug: indium In 111 ibritumomab tiuxetan Drug: prednisone Drug: rituximab Drug: vincristine sulfate Drug: yttrium Y 90 ibritumomab tiuxetan	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Filgrastim Prednisone Vincristine sulfate Vincristine Rituximab Ibritumomab tiuxetan Darbepoetin alfa Indium in 111 oxyquinoline

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control
Official Title:	A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

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

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Conversion rate to complete remission [ Designated as safety issue: No ]

Estimated Enrollment:	65
Study Start Date:	February 2003
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the progression-free and overall survival of patients age 60 and over with previously untreated diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combined with yttrium Y 90 ibritumomab tiuxetan.
Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen.
Determine the response rate of patients treated with this regimen.
Determine the red blood cell transfusion requirements, change in hemoglobin from baseline, and incidence of anemia with prophylactic darbepoetin alfa support in patients treated with this regimen.
Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP.
Determine the effect of darbepoetin alfa on the quality of life of these patients.

OUTLINE: This is an open-label, nonrandomized study.

Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0.

Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7.

Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diffuse large B-cell lymphoma, including any of the following subtypes:
- Centroblastic
- Immunoblastic
- T-cell/histiocyte-rich
- Lymphomatoid granulomatosis type
- Anaplastic large B-cell
- Plasmablastic
- Mediastinal
- Intravascular large B-cell lymphoma
Previously untreated
High-intermediate or high-risk disease, defined by an age-adjusted international prognostic index score of 2 or 3 (with 1 point each assigned for a ECOG greater than 1/Karnofsky less than 80%, lactate dehydrogenase greater than normal, and stage III or IV)
Lymphomas with discordant histology and a diffuse large B-cell component are eligible
Must have an initial diagnostic specimen that is CD20+
At least Ann Arbor stage II disease
- No confinement of disease to an involved-field radiotherapy port (stage I or limited stage II disease)
Bidimensionally measurable disease with at least 1 lymph node at least 2.0 cm by 2.0 cm by physical examination, CT scan, or positron-emission tomography
Bone marrow cellularity greater than 15%
No known brain or leptomeningeal metastases
No primary effusion lymphomas

PATIENT CHARACTERISTICS:

Age

60 and over* NOTE: *Patients 60 to 65 years of age must be deemed ineligible for autologous stem cell transplantation

Performance status

Karnofsky 50-100%

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin no greater than 2.0 mg/dL (except for Gilbert's disease)

Renal

Creatinine no greater than 1.5 mg/dL* OR
Creatinine clearance greater than 50 mL/min* NOTE: *Patients not meeting either criterion but who have renal insufficiency directly related to lymphomatous involvement of the kidneys or renal collecting system are allowed

Cardiovascular

Cardiac ejection fraction at least 50% by echocardiogram
No acute myocardial infarction within the past 3 months
No uncontrolled hypertension
No New York Heart Association class III or IV congestive heart failure
No unstable angina pectoris

Other

Not pregnant or nursing
Fertile patients must use effective contraception
HIV negative
B12 and folate greater than the lower limit of normal
Transferrin saturation at least 15%
Ferritin greater than 10 µg/L
At least 6 weeks since prior RBC donation
No active seizure disorder
- Prior seizure disorder allowed if free of antiseizure medication and evidence of seizure activity for the past 5 years
No concurrent uncontrolled medical problems that would preclude administration of chemotherapy or radioimmunotherapy
No other concurrent malignancy treated with chemotherapy or radiotherapy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 4 weeks since prior RBC transfusion
No prior biologic therapy
No other concurrent biologic therapy

Chemotherapy

No prior chemotherapy (one course of R-CHOP allowed)
No other concurrent standard or investigational chemotherapy

Endocrine therapy

No more than 7 consecutive days of prior steroids (premedication allowed for prior intravenous contrast allergy)
No other concurrent corticosteroids

Radiotherapy

No prior radiotherapy

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00058422

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Paul A. Hamlin, MD

Memorial Sloan-Kettering Cancer Center

More Information

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

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Paul A. Hamlin )
Study ID Numbers:	CDR0000288830, MSKCC-02090
Study First Received:	April 7, 2003
Last Updated:	October 24, 2008
ClinicalTrials.gov Identifier:	NCT00058422
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Study placed in the following topic categories:

Prednisone
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Darbepoetin alfa
Vincristine
Cyclophosphamide
Doxorubicin
Antibodies, Monoclonal

Lymphoma, B-Cell
Lymphoma, large-cell
Lymphatic Diseases
Antibodies
B-cell lymphomas
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Hematologic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Immune System Diseases

Antineoplastic Agents, Hormonal
Hematinics
Mitosis Modulators
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009