Radiolabeled Monoclonal Antibody in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Terminated

CT.gov ID

NCT00033423

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL).
Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen.
Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen.
Determine the antitumor response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan.

Patients receive rituximab IV once weekly on weeks 1-4. After 4 doses of rituximab, patients without bone marrow involvement and cellularity greater than 50% expected receive rituximab IV once weekly on weeks 6 and 7 and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes with the final dose of rituximab (day 43).

Cohorts of 5-6 patients receive escalating dose of yttrium Y 90 ibritumomab tiuxetan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 5 or 3 of 6 patients experience dose-limiting toxicity.

Patients are followed at 6 and 12 weeks, every 2-3 months for 2 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I, Multicenter, Open Label, Dose Escalation Of 90Y-Zevalin Radioimmunotherapy Using A Modified Treatment Regimen For Relapsed Or Refractory CD20+ B-Cell (Follicular/Transformed) Non-Hodgkin's Lymphoma

Study Start Date :

Aug 1, 2001

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 First radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan
Experimental: Cohort II Second radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan
Experimental: Cohort III Third radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan
Experimental: Cohort IV Fourth radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan
Experimental: Cohort V MTD radiation dose regimen of yttrium Y 90 ibritumomab tiuxetan	Biological: rituximab Radiation: yttrium Y 90 ibritumomab tiuxetan

Outcome Measures

Primary Outcome Measures

Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan when administered in combination with rituximab in patients with relapsed or refractory low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL). [baseline through 4 years]

Secondary Outcome Measures

Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen [baseline through 4 years]
Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen. [baseline through 4 years]
Determine the antitumor response in patients treated with this regimen. [baseline through 4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed low-grade, follicular, or transformed CD20-positive B-cell non-Hodgkin's lymphoma (NHL)
Relapsed after prior chemotherapy OR chemotherapy-resistant disease
Failed at least 1 prior chemotherapy regimen
CD20-positive B-cell population in lymph nodes or bone marrow for International Working Formulation A (small lymphocytic lymphoma) and transformed NHL
Bone marrow involvement with lymphoma less than 25% bilaterally
No impaired bone marrow reserve defined as at least 1 of the following criteria:
Prior myeloablative therapies with bone marrow transplantation or peripheral blood stem cell rescue
Platelet count less than 100,000/mm3
Bone marrow cellularity no greater than 15%
Marked reduction in bone marrow precursors of one or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid)
Failed prior stem cell collection
No CNS lymphoma, chronic lymphocytic lymphoma, or HIV or AIDS-related lymphoma
No diffuse small lymphocytic/marginal zone lymphoma with lymphocyte count greater than 5,000/mm^3
No pleural effusion 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:

19 and over

Performance status:

WHO 0-2

Life expectancy:

At least 6 months

Hematopoietic:

See Disease Characteristics
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hematocrit greater than 30%
Hemoglobin greater than 9.0 g/dL

Hepatic:

Bilirubin no greater than 1.5 mg/dL

Renal:

Creatinine no greater than 1.5 mg/dL

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after study participation
No anti-murine antibody reactivity if prior exposure to murine antibodies or proteins
No other primary malignancy
No other serious nonmalignant disease or infection that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
No prior radioimmunotherapy
Prior rituximab allowed if more than 6 months to progression after an objective response
At least 6 weeks since prior rituximab
At least 3 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
Recovered from prior immunotherapy

Chemotherapy:

See Disease Characteristics
No prior fludarabine
At least 3 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No concurrent chemotherapy

Endocrine therapy:

At least 3 weeks since prior anticancer endocrine therapy
No concurrent high-dose systemic corticosteroids (e.g., 50 mg or more of prednisone as a single dose or 50 mg or less of prednisone for more than 6 doses)

Radiotherapy:

No prior radiotherapy to more than 25% of active bone marrow (involved field or regional)
At least 3 weeks since prior anticancer radiotherapy and recovered

Surgery:

At least 4 weeks since prior surgery (except diagnostic surgery) and recovered

Other:

No other concurrent anticancer therapy
Concurrent oral anticoagulant therapy allowed if platelet count is at least 30,000/mm3

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham	Birmingham	Alabama	United States	35294
2	Stanford Comprehensive Cancer Center - Stanford	Stanford	California	United States	94305
3	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905