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Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

Phase I/II Study of Two Sequential Doses of IDEC-Y2B8 in Patients With Relapsed Low-Grade and Follicular Non-Hodgkin's Lymphoma


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.


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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan (Phase I)

Outcome Description:

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.

Outcome Time Frame:

At 8 weeks

Safety Issue:

Yes

Principal Investigator

Thomas Witzig

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00008

NCT ID:

NCT00012298

Start Date:

April 2001

Completion Date:

Related Keywords:

  • 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
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin
  • Waldenstrom Macroglobulinemia
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone

Name

Location

Mayo ClinicRochester, Minnesota  55905