Lymphoma
Conditions
Keywords
contiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, stage I grade 1 follicular lymphoma, stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, splenic marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma
Brief summary
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.
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.
Interventions
BIOLOGICALrituximab
RADIATIONyttrium Y 90 ibritumomab tiuxetan
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks | 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. |
| EFS | 1 year | Event = Death, second malignancy , disease progression. |
Countries
United States
Participant flow
Pre-assignment details
12 patients were recruited and signed consent. 3 patient were ineligible and were not treated. The total number treated is nine
Participants by arm
| Arm | Count |
|---|---|
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 9 |
| other Total, other adverse events | 4 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
EFS
Event = Death, second malignancy , disease progression.
Time frame: 1 year
Population: The study was terminated early
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | EFS | Progression | 3 Participants |
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | EFS | alive in remission | 5 Participants |
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | EFS | Second malignancy | 1 Participants |
Primary
Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 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.
Time frame: 14 weeks
Population: The trial closed prematurely secondary to the company that produced the agent being sold to another company and the agent not being available to treat the full number of patients in this trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks | CR | 9 Participants |
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks | PR | 0 Participants |
| Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan | Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks | PD | 0 Participants |