Radiolabeled Monoclonal Antibody Plus Rituximab With and Without Filgrastim and Interleukin-11 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT ID: NCT00012298

Last Updated: 2018-08-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-04-30
• Study Completion Date: 2010-04-30

Brief Summary

Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibody therapy and rituximab with and without filgrastim and interleukin-11 in treating patients who have relapsed or refractory non-Hodgkin's lymphoma. Radiolabeled monoclonal antibodies can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Biological therapies such as filgrastim and interleukin-11 use different ways to stimulate the immune system and stop cancer cells from growing.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of yttrium Y 90 ibritumomab tiuxetan (IDEC-90Y2B8) administered with rituximab with and without filgrastim (G-CSF) and interleukin-11 (IL-11) in patients with relapsed low-grade or follicular CD20+ non-Hodgkin's lymphoma. (Phase I) II. Determine the toxicity of this regimen in these patients. III. Determine the response rate in patients treated with this regimen. IV. Compare tumor and normal organ dosimetry with positron emission tomography and computerized tomography scans, subsequent tumor response, and normal organ toxicity by utilizing indium In 111 ibritumomab tiuxetan radioimmunoconjugate scans before each IDEC-90Y2B8 dose in these patients. (Phase I) V. Determine the immune response to this regimen, in terms of human anti-mouse and human anti-chimeric antibody formation, in these patients. (Phase I) VI. Determine whether G-CSF and IL-11 can ameliorate the effect of the MTD of IDEC-90Y2B8 on bone marrow function in these patients. (Phase I) VII. Determine progression-free survival at 3 years. (Phase II)

OUTLINE:

PHASE I: Patients receive rituximab IV on days 1 and 8, indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 (for radioimaging), and IDEC-90Y2B8 IV over 10 minutes on day 8. Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) of IDEC-90Y2B8 is determined, patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning when absolute neutrophil count is less than 1,500/mm3 and continuing until blood counts recover. Patients also receive interleukin-11 (IL-11) SC beginning when platelet count is less than 75,000/mm^3 and continuing until blood counts recover. Patients undergo PBSC transplantation only if marrow recovery is inadequate.

Cohorts of 3-6 patients receive escalating doses of IDEC-90Y2B8 until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to determine the MTD of this radioimmunotherapy with the addition of the prophylactic cytokines, G-CSF and IL-11.

PHASE II: Patients receive rituximab, indium In 111 ibritumomab tiuxetan, and IDEC-90Y2B8 IV as determined at the MTD in phase I. Treatment repeats 24-36 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

Conditions

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (radiolabeled monoclonal antibody therapy)

Patients receive rituximab IV on days 1 and 8, indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1, and yttrium Y 90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) and interleukin-11 SC until blood counts recover.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

yttrium Y 90 ibritumomab tiuxetan

Intervention Type: BIOLOGICAL

Given IV

indium In 111 ibritumomab tiuxetan

Intervention Type: BIOLOGICAL

Given IV

oprelvekin

Intervention Type: BIOLOGICAL

Given subcutaneously

filgrastim

Intervention Type: BIOLOGICAL

Given subcutaneously

Interventions

rituximab

Given IV

Intervention Type: BIOLOGICAL

yttrium Y 90 ibritumomab tiuxetan

Given IV

Intervention Type: BIOLOGICAL

indium In 111 ibritumomab tiuxetan

Given IV

Intervention Type: BIOLOGICAL

oprelvekin

Given subcutaneously

Intervention Type: BIOLOGICAL

filgrastim

Given subcutaneously

Intervention Type: BIOLOGICAL

Other Intervention Names

IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; 90Y ibritumomab tiuxetan; IDEC Y2B8; Y90 Zevalin; Y90-labeled ibritumomab tiuxetan; IDEC-In2B8; adipogenesis inhibitory factor; IL-11; interleukin 11; Neumega; G-CSF; Neupogen

Eligibility Criteria

Inclusion Criteria

• Histologically proven relapsed or refractory low-grade or follicular CD+ non-Hodgkin lymphoma, including 1 of the following:

• Small lymphocytic lymphoma
• Lymphoplasmacytoid lymphoma
• Follicular center lymphoma (grades I, II, and III)
• Extranodal marginal zone B-cell lymphoma
• Nodal marginal zone B-cell lymphoma
• Splenic marginal zone B-cell lymphoma (monocytoid B-cell lymphoma)
• Less than 25% bone marrow involvement of cellular marrow with lymphoma by bilateral bone marrow aspirate and biopsy
• ECOG performance status 0-2
• Bidimensionally measurable disease with at least 1 lesion >= 2 cm in the greatest diameter
• No prior myeloablative therapy with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
• No concurrent corticosteroid therapy, except prednisone (or equivalent) for adrenal failure or < 20mg of prednisone daily
• No prior external beam radiotherapy to >25% of active bone marrow
• More than 4 weeks since prior surgery other than diagnostic surgery
• No other concurrent myelosuppressive antineoplastic agents
• No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan or iodine I 131 monoclonal antibody tositumomab or Lym-1
• No CNS lymphoma
• No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia
• No HIV or AIDS-related lymphoma
• No pleural effusion or ascites with lymphoma cells
• No active infection
• No other serious non-malignant disease that would preclude study participation
• No other active primary malignancy
• No known human anti-mouse or human anti-chimeric antibody
• No prior skin rash (e.g., Stevens-Johnsons syndrome or toxic epidermal necrolysis) from rituximab therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 150,000/mm^3
• Total lymphocyte count < 5,000/mm^3 for patients with small lymphocytic lymphoma
• Bilirubin =< 2 mg/dL
• Creatinine =< 2 mg/dL

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Witzig

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2009-00008

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000068503

Identifier Type: -

Identifier Source: secondary_id

MC998C

Identifier Type: OTHER

Identifier Source: secondary_id

312

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00008

Identifier Type: -

Identifier Source: org_study_id

NCT01646879

Identifier Type: -

Identifier Source: nct_alias