A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
60 Years
N/A
Both
Lymphoma
Trial Information
A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Paul A. Hamlin, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
02-090
NCT ID:
NCT00058422
Start Date:
February 2003
Completion Date:
February 2014
Related Keywords:
- Lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage IV adult diffuse large cell lymphoma
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
