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

This study has been terminated.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00033423
First received: April 9, 2002
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Lymphoma
Biological: rituximab
Radiation: yttrium Y 90 ibritumomab tiuxetan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

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). [ Time Frame: baseline through 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the toxicity of different doses of yttrium Y 90 ibritumomab tiuxetan in patients treated with this regimen [ Time Frame: baseline through 4 years ] [ Designated as safety issue: Yes ]
  • Determine the frequency of reversal of bone marrow involvement with NHL in patients treated with this regimen. [ Time Frame: baseline through 4 years ] [ Designated as safety issue: No ]
  • Determine the antitumor response in patients treated with this regimen. [ Time Frame: baseline through 4 years ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: August 2001
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00033423

Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Stanford Comprehensive Cancer Center - Stanford
Stanford, California, United States, 94305
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Study Chair: Andres Forero-Torres, MD, CSU University of Alabama at Birmingham
  More Information

Publications:
Forero-Torres A, Besh S, Knox S, et al.: Higher doses of Rituxan alter pharmacokinetics and biodistribution of Zevalin but may increase responses; a preliminary report of a phase I study of Zevalin using a modified treatment regimen for relapsed or refractory CD20+ B-Cell follicular/transformed non-Hodgkins lymphoma. [Abstract] Blood 102 (11 Pt 1): A-1483, 2003.

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00033423     History of Changes
Other Study ID Numbers: CDR0000069282, UAB-0127, UAB-F010806018, NCI-G02-2053
Study First Received: April 9, 2002
Last Updated: December 12, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Alabama at Birmingham:
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent marginal zone lymphoma
recurrent 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:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 29, 2014