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A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

Phase 2
60 Years
Open (Enrolling)

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Trial Information

A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma


- 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

- 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


- 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



- 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


- Not specified


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


- 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


- 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


- 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


Biologic therapy

- At least 4 weeks since prior RBC transfusion

- No prior biologic therapy

- No other concurrent biologic therapy


- 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


- No prior radiotherapy


- Not specified

Type of Study:


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:


Principal Investigator

Paul A. Hamlin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




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



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