Brief Title
Radiolabeled Monoclonal Antibody Plus Rituximab With and Without Filgrastim and Interleukin-11 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum Tolerated Dose (MTD) of Yttrium Y-90 Ibritumomab Tiuxetan (Y2B8) With and Without Filgrastim (G-CSF) and Interleukin-11 (IL-11) (Phase I)
Secondary Outcome
Association Between the Amounts of Tumor Radiation Indicated by the In2B8 Scan and Tumor Response (Phase I)
Condition
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intervention
rituximab
Study Arms / Comparison Groups
Treatment (radiolabeled monoclonal antibody therapy)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
81
Start Date
April 2001
Completion Date
April 2010
Primary Completion Date
April 2010
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Thomas Witzig, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00012298
Organization ID
NCI-2009-00008
Secondary IDs
NCI-2009-00008
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Thomas Witzig, Principal Investigator, Mayo Clinic
Verification Date
July 2018