Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care, Treatment	Closed	60 and over	NCI	MSKCC-02090 NCT00058422

Objectives

1. 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.
2. 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.
3. Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen.
4. Determine the response rate of patients treated with this regimen.
5. 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.
6. Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP.
7. Determine the effect of darbepoetin alfa on the quality of life of these patients.

Entry 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

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

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

Expected Enrollment

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

Outcomes

Overall survival
Progression-free survival
Event-free survival

Conversion rate to complete remission

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Paul Hamlin, MD, Protocol chair		Ph: 212-639-6143; 800-525-2225 Email: hamlinp@mskcc.org

Registry Information
Official Title		A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients with Previously Untreated Diffuse Large B-Cell Lymphoma
Trial Start Date		2003-02-10
Trial Completion Date		2010-02-10 (estimated)
Registered in ClinicalTrials.gov		NCT00058422
Date Submitted to PDQ		2003-02-28
Information Last Verified		2008-10-23
NCI Grant/Contract Number		CA08748

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