Clinical trial NCT00012298: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Yttrium Y-90 Ibritumomab Tiuxetan (Y2B8) With and Without Filgrastim (G-CSF) and Interleukin-11 (IL-11) (Phase I)
timeFrame: At 8 weeks
measure: Toxicity of Single-dose Y2B8 Radioimmunotherapy With and Without the Use of Growth Factors (Phase I)
timeFrame: Assessed up to week 24
measure: Proportion of Patients Who Receive 2 Sequential Doses of Y2B8 Immunotherapy and Are Progression-free (Phase II)
timeFrame: At 3 years
Secondary outcomes:
measure: Association Between the Amounts of Tumor Radiation Indicated by the In2B8 Scan and Tumor Response (Phase I)
timeFrame: At week 12
measure: Association Between In2B8 Scan and Positron Emission Tomography Scan Results (Phase I)
timeFrame: At week 12
measure: Appearance of Tumor and Normal Organ Images on the Second In2B8 Scan (Phase I)
timeFrame: At week 12
measure: Survival (Phase II)
timeFrame: From registration to death due to any cause, assessed up to 5 years
measure: Time to Disease Progression (Phase II)
timeFrame: From registration to the earliest date documentation of>disease progression, assessed up to 5 years
measure: Tumor Response Rate (Phase II)
timeFrame: Assessed up to 5 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Thomas Witzig
role: PRINCIPAL_INVESTIGATOR
References: