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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00012298
First received: March 3, 2001
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
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
Biological: rituximab
Biological: yttrium Y 90 ibritumomab tiuxetan
Biological: indium In 111 ibritumomab tiuxetan
Biological: oprelvekin
Biological: filgrastim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan (Phase I) [ Time Frame: At 8 weeks ] [ Designated as safety issue: Yes ]
    If at any time 2 or more patients (of a maximum of 6) at any dose level experience DLT, then the MTD will be defined as the previous dose level.

  • Toxicity of single-dose Y2B8 radioimmunotherapy with and without the use of growth factors (Phase I) [ Time Frame: Assessed up to week 24 ] [ Designated as safety issue: Yes ]
    Evaluated using the Common Toxicity Criteria (CTC) version 2.0. Presented primarily in a descriptive fashion.

  • Proportion of patients who receive 2 sequential doses of Y2B8 immunotherapy and are progression-free (Phase II) [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    Estimated by the number of successes divided by the total number of evaluable patients. Exact binomial confidence intervals for the true success proportion will be calculated.


Secondary Outcome Measures:
  • Association between the amounts of tumor radiation indicated by the In2B8 scan and tumor response (Phase I) [ Time Frame: At week 12 ] [ Designated as safety issue: No ]
    Assessed using a correlated logistic regression model and generalized estimating equations (GEE). Covariates such as dose level and use of prophylactic cytokines may also be included in this model. A Wilcoxon test will be used to assess the equality of the distributions of the continuous levels of predicted tumor radiation from the In2B8 scans by response.

  • Association between In2B8 scan and positron emission tomography scan results (Phase I) [ Time Frame: At week 12 ] [ Designated as safety issue: No ]
    Explored using a contingency table and sensitivity and specificity will be calculated using 90% exact confidence intervals.

  • Appearance of tumor and normal organ images on the second In2B8 scan (Phase I) [ Time Frame: At week 12 ] [ Designated as safety issue: No ]
    Calculated from the serial gamma camera images. Compared using a signed-rank-test. Scatter plots will be used to further explore relationships between these residence times and Bland- Altman methods can be used to assess the agreement between the first and second In2B8 scan residence times.

  • Survival (Phase II) [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.

  • Time to disease progression (Phase II) [ Time Frame: From registration to the earliest date documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier.

  • Tumor response rate (Phase II) [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]
    Calculated by the number of tumor responses divided by the total number of evaluable patients. An exact binomial confidence interval will be calculated.


Enrollment: 73
Study Start Date: April 2001
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: rituximab
Given IV
Biological: yttrium Y 90 ibritumomab tiuxetan
Given IV
Biological: indium In 111 ibritumomab tiuxetan
Given IV
Biological: oprelvekin
Given subcutaneously
Biological: filgrastim
Given subcutaneously

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00012298

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Witzig Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00012298     History of Changes
Obsolete Identifiers: NCT01646879
Other Study ID Numbers: NCI-2009-00008, NCI-2009-00008, CDR0000068503, MC998C, 312
Study First Received: March 3, 2001
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Antibodies, Monoclonal
Lenograstim
Rituximab
Oprelvekin
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014