Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Non-Hodgkin's Lymphoma
A Phase II Study of Yttrium-90-Labeled Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as First Line Treatment in Indolent Non-Hodgkin's Lymphoma
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others, such as yttrium Y 90 ibritumomab tiuxetan, find cancer cells and help kill them or carry cancer-killing substances to them without harming normal cells. Giving rituximab together with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving rituximab together with yttrium Y 90 ibritumomab tiuxetan works in treating patients with indolent non-Hodgkin's lymphoma.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- Determine 12-week overall and complete response rate in patients with indolent non-Hodgkin's lymphoma treated with rituximab and yttrium Y 90 ibritumomab tiuxetan as first-line treatment.
Secondary
- Determine 1-year event-free survival of patients treated with this regimen.
- Determine time to progression and time to next antilymphoma therapy in patients treated with this regimen.
- Determine the molecular response rate in patients treated with this regimen.
- Determine the hematological and non-hematological toxicity of this regimen in these patients.
- Assess the quality of life of patients treated with this regimen.
OUTLINE: This is an open-label, multicenter study.
Patients receive rituximab IV followed, no more than 4 hours later, by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day 1. If biodistribution is acceptable, patients receive rituximab IV followed, no more than 4 hours later, by a single dose of yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, or 9 in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, weeks 6, 10, and 14, every 3 months for 2 years, and then every 6 months for 2 years.
After completion of study treatment, patients are followed weekly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 18-28 patients will be accrued for this study within 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
-
-
New Hampshire
-
Lebanon, New Hampshire, United States, 03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
-
-
Vermont
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Burlington, Vermont, United States, 05401-3498
- Vermont Cancer Center at University of Vermont
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed indolent non-Hodgkin's lymphoma (NHL), including 1 of the following histologic subtypes:
- Grade1 or 2 follicular lymphoma
- Small lymphocytic lymphoma (SLL)
- Marginal zone B-cell lymphoma
- CD20-positive disease confirmed by immunohistochemistry or flow cytometry
Bidimensionally measurable disease
- At least 1 lesion measuring ≥ 2.0 cm in a single dimension by CT scan
- Less than 25% bone marrow involvement with lymphoma by bilateral iliac crest bone marrow aspiration and biopsy within the past 6 weeks
No clinically significant impaired bone marrow reserve as evidenced by any of the following:
Hypocellular marrow, as evidenced by 1 of the following:
- ≤ 15% cellularity
- Marked reduction in bone marrow precursors
- Platelet count < 100,000/mm^3
- Absolute neutrophil count < 1,500/mm^3
- History of failed stem cell collection
- Prior myeloablative therapy
- No greater than 5,000/mm^3 circulating tumor cells in peripheral blood
Requires antilymphoma therapy, as indicated by any of the following:
- Systemic symptoms
- B symptoms
- Cytopenias
- Malaise
- Organ compromise
- Discomfort
- Pain
- Disfigurement
- Rapidly progressive disease
- Undue anxiety related to not receiving treatment
- No transformation to intermediate or high-grade NHL
- No known brain metastases or CNS involvement by lymphoma NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- ECOG 0-2 OR
- WHO 0-2 OR
- Karnofsky 70-100%
Life expectancy
- More than 3 months
Hematopoietic
- See Disease Characteristics
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Lymphocyte count < 5,000/mm^3 (for patients with SLL )
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
Renal
- Creatinine ≤ 2.0 mg/dL OR
- Creatinine clearance > 60 mL/min
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Immunologic
- No anti-murine antibody reactivity (in patients with prior exposure to murine antibodies or proteins)
- No ongoing or active infection
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to yttrium Y 90 ibritumomab tiuxetan
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 1 year after study treatment
- No other active malignancy except non-melanoma skin cancer
- No other serious nonmalignant disease that would preclude study participation
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior pegfilgrastim
- More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior external beam radiotherapy to > 25% of active bone marrow (involved field or regional)
Surgery
- More than 4 weeks since prior major surgery except diagnostic surgery
Other
- No prior systemic antilymphoma therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
- No other concurrent investigational agents
- No other concurrent antilymphoma therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks
Time Frame: 14 weeks
|
INTERNATIONAL WORKSHOP RESPONSE CRITERIA FOR NON HODGKIN'S LYMPHOMA Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non Hodgkin's lymphoma. J Clin Oncol 1999;17(4):1244-53. |
14 weeks
|
|
EFS
Time Frame: 1 year
|
Event = Death, second malignancy , disease progression.
|
1 year
|
Collaborators and Investigators
Investigators
- Study Chair: Robin Joyce, MD, Beth Israel Deaconess Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage I grade 1 follicular lymphoma
- stage I grade 2 follicular lymphoma
- contiguous stage II grade 1 follicular lymphoma
- contiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- noncontiguous stage II marginal zone lymphoma
- stage I marginal zone lymphoma
- stage I small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- contiguous stage II marginal zone lymphoma
- contiguous stage II small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Lymphoma, Non-Hodgkin
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- 2004P000044
- CDR0000409723 (Registry Identifier: PDQ (Physician Data Query))
- NCI-2011-02445 (Registry Identifier: CTRP (Clinical Trials Reporting System))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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