Clinical trial NCT00110149: Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Yttrium-90-Labeled Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy as First Line Treatment in Indolent Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma
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
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
First posted: 2005-05-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Response Rate (Complete Response, Unconfirmed Complete Response, and Partial Response) at 12 Weeks
timeFrame: 14 weeks
measure: EFS
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Robin Joyce, MD
role: STUDY_CHAIR
References: