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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00012298
• Collaborator: (none)
• Enrollment: 81
• Location: 1
• Arm: 1
• Duration (Months): 108
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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

Detailed Description

PRIMARY OBJECTIVES:

1. 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)
2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Apr 1, 2001
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

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; Other Names: IDEC-C2B8 IDEC-C2B8 monoclonal antibody Mabthera MOAB IDEC-C2B8 Rituxan ; Biological: yttrium Y 90 ibritumomab tiuxetan; Given IV; Other Names: 90Y ibritumomab tiuxetan IDEC Y2B8 Y90 Zevalin Y90-labeled ibritumomab tiuxetan ; Biological: indium In 111 ibritumomab tiuxetan; Given IV; Other Names: IDEC-In2B8 ; Biological: oprelvekin; Given subcutaneously; Other Names: adipogenesis inhibitory factor IL-11 interleukin 11 Neumega ; Biological: filgrastim; Given subcutaneously; Other Names: G-CSF Neupogen

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Yttrium Y-90 Ibritumomab Tiuxetan (Y2B8) With and Without Filgrastim (G-CSF) and Interleukin-11 (IL-11) (Phase I) [At 8 weeks]

   This study is a series of 3 single-arm phase-I trials designed to determine the maximum tolerated dose (MTD) of a 2-cycle combination regimen containing Rituxan + Y2B8 radioimmunotherapy with and without the use of G-CSF and IL-11. Trial 1 will determine the Y2B8 MTD in the combined regimen without growth factors. Trial 2 will evaluate the combined regimen with growth factors. Trial 3 starts IL-11 earlier (when platelet count drops below 150000) and reduces the dosing interval to twice weekly. > Dose-limiting toxicity (DLT) is defined as an adverse event in the second cycle attributed to treatment and meeting the following criteria: Grade 4 ANC or platelet decrease for 14 days, or grade 3 for 28 days, or any other grade 3 Non-Heme event. > 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 during that trial. The number of patients with a DLT are reported here.

2. Toxicity of Single-dose Y2B8 Radioimmunotherapy With and Without the Use of Growth Factors (Phase I) [Assessed up to week 24]

   Evaluated using the Common Toxicity Criteria (CTC) version 2.0. This data is presented as the number of patients reporting grade 3 or higher, grade 4 or higher, or grade 5 adverse events regardless of event attribution.

3. Proportion of Patients Who Receive 2 Sequential Doses of Y2B8 Immunotherapy and Are Progression-free (Phase II) [At 3 years]

   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

1. Association Between the Amounts of Tumor Radiation Indicated by the In2B8 Scan and Tumor Response (Phase I) [At week 12]

   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.

2. Association Between In2B8 Scan and Positron Emission Tomography Scan Results (Phase I) [At week 12]

   Explored using a contingency table and sensitivity and specificity will be calculated using 90% exact confidence intervals.

3. Appearance of Tumor and Normal Organ Images on the Second In2B8 Scan (Phase I) [At week 12]

   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.

4. Survival (Phase II) [From registration to death due to any cause, assessed up to 5 years]

   Estimated using the method of Kaplan-Meier.

5. Time to Disease Progression (Phase II) [From registration to the earliest date documentation of>disease progression, assessed up to 5 years]

   Estimated using the method of Kaplan-Meier.

6. Tumor Response Rate (Phase II) [Assessed up to 5 years]

   Calculated by the number of tumor responses divided by the total number of evaluable patients. An exact binomial confidence interval will be calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Thomas Witzig, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00012298
• Other Study ID Numbers: NCI-2009-00008; NCI-2009-00008; CDR0000068503; MC998C; 312; NCT01646879
• First Posted: Jan 27, 2003
• Last Update Posted: Aug 9, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia; Recurrence; Rituximab; Oprelvekin; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	Phase I is a series of three single-arm trials: Trial 1 will determine the Y2B8 MTD without growth factors, Trial 2 will test the regimen with G-CSF and IL-11 added to the treatment, and Trial 3 tests different levels of IL-11 in the regimen.

Arm/Group Title	Treatment: Trial 1, Dose Level 1	Treatment: Trial 1, Dose Level 2	Treatment: Trial 2, Dose Level 3	Treatment: Trial 2, Dose Level 4	Treatment: Trial 3, Dose Level 5	Treatment: Trial 3, Dose Level 6	Treatment : Phase II (Dose Level 6)
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8.	Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Period Title: Overall Study
STARTED	11	7	9	4	5	6	39
COMPLETED	11	7	9	4	5	6	39
NOT COMPLETED	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Treatment: Trial 1, Dose Level 1	Treatment: Trial 1, Dose Level 2	Treatment: Trial 2, Dose Level 3	Treatment: Trial 2, Dose Level 4	Treatment: Trial 3, Dose Level 5	Treatment: Trial 3, Dose Level 6	Treatment : Phase II (Dose Level 6)	Total
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Total of all reporting groups
Overall Participants	11	7	9	4	5	6	39	81
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	56	52	51	46	59	58	58
Sex: Female, Male (Count of Participants)
Female	4 36.4%	4 57.1%	2 22.2%	2 50%	3 60%	1 16.7%	17 43.6%	33 40.7%
Male	7 63.6%	3 42.9%	7 77.8%	2 50%	2 40%	5 83.3%	22 56.4%	48 59.3%
Region of Enrollment (participants) [Number]
Saudi Arabia	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	1 1.2%
Croatia	1 9.1%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.2%
United States	10 90.9%	7 100%	9 100%	3 75%	5 100%	6 100%	39 100%	79 97.5%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Yttrium Y-90 Ibritumomab Tiuxetan (Y2B8) With and Without Filgrastim (G-CSF) and Interleukin-11 (IL-11) (Phase I)
Description	This study is a series of 3 single-arm phase-I trials designed to determine the maximum tolerated dose (MTD) of a 2-cycle combination regimen containing Rituxan + Y2B8 radioimmunotherapy with and without the use of G-CSF and IL-11. Trial 1 will determine the Y2B8 MTD in the combined regimen without growth factors. Trial 2 will evaluate the combined regimen with growth factors. Trial 3 starts IL-11 earlier (when platelet count drops below 150000) and reduces the dosing interval to twice weekly. > Dose-limiting toxicity (DLT) is defined as an adverse event in the second cycle attributed to treatment and meeting the following criteria: Grade 4 ANC or platelet decrease for 14 days, or grade 3 for 28 days, or any other grade 3 Non-Heme event. > 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 during that trial. The number of patients with a DLT are reported here.
Time Frame	At 8 weeks

Outcome Measure Data

Analysis Population Description

DLTs were determined in the second cycle of combined treatment. Only Phase I patients that were evaluated after 2 cycles of treatment are included in this evaluation. Two patients at Dose Level 1, 1 patient at Dose Level 2, 4 patients at Dose Level 3, and 1 patient at Dose Level 5 were not evaluated for MTD.

Arm/Group Title	Treatment: Trial 1, Dose Level 1	Treatment: Trial 1, Dose Level 2	Treatment: Trial 2, Dose Level 3	Treatment: Trial 2, Dose Level 4	Treatment: Trial 3, Dose Level 5	Treatment: Trial 3, Dose Level 6
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8	Patients receive: Cycle 1: 50 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Measure Participants	9	6	5	4	4	6
Number [Patients reporting Dose-Limiting Events]	0	2	0	2	0	1

2. Primary Outcome

Title	Toxicity of Single-dose Y2B8 Radioimmunotherapy With and Without the Use of Growth Factors (Phase I)
Description	Evaluated using the Common Toxicity Criteria (CTC) version 2.0. This data is presented as the number of patients reporting grade 3 or higher, grade 4 or higher, or grade 5 adverse events regardless of event attribution.
Time Frame	Assessed up to week 24

Outcome Measure Data

Analysis Population Description

All patients that were evaluated for adverse events after at least one cycle of treatment were used in this analysis.

Arm/Group Title	Treatment: Trial 1, Dose Level 1	Treatment: Trial 1, Dose Level 2	Treatment: Trial 2, Dose Level 3	Treatment: Trial 2, Dose Level 4	Treatment: Trial 3, Dose Level 5	Treatment: Trial 3, Dose Level 6
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 12-24 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Measure Participants	11	7	9	4	5	6
Grade 3+ Adverse Event	9 81.8%	6 85.7%	8 88.9%	4 100%	5 100%	6 100%
Grade 4+ Adverse Event	2 18.2%	5 71.4%	2 22.2%	2 50%	1 20%	1 16.7%
Grade 5 Adverse Event	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Proportion of Patients Who Receive 2 Sequential Doses of Y2B8 Immunotherapy and Are Progression-free (Phase II)
Description	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.
Time Frame	At 3 years

Outcome Measure Data

Analysis Population Description

Forty-five patients were registered to Dose Level 6 (39 patients registered to the Phase II portion and 6 patients registered to Dose Level 6 in the Phase I portion). Of the 45 patients, 33 patients received 2 sequential doses of Y2B8 and were evaluable for this endpoint.

Arm/Group Title	Treatment : Dose Level 6
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Measure Participants	33
Number (95% Confidence Interval) [proportion of participants]	.45 4.1%

4. Secondary Outcome

Title	Association Between the Amounts of Tumor Radiation Indicated by the In2B8 Scan and Tumor Response (Phase I)
Description	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.
Time Frame	At week 12

Outcome Measure Data

Analysis Population Description

Not collected. Study team decision not to analyze this endpoint.

Arm/Group Title	Treatment (Radiolabeled Monoclonal Antibody Therapy)
Arm/Group 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. rituximab: Given IV yttrium Y 90 ibritumomab tiuxetan: Given IV indium In 111 ibritumomab tiuxetan: Given IV oprelvekin: Given subcutaneously filgrastim: Given subcutaneously
Measure Participants	0

5. Secondary Outcome

Title	Association Between In2B8 Scan and Positron Emission Tomography Scan Results (Phase I)
Description	Explored using a contingency table and sensitivity and specificity will be calculated using 90% exact confidence intervals.
Time Frame	At week 12

Outcome Measure Data

Analysis Population Description

Not collected. Study team decision not to analyze this endpoint.

Arm/Group Title	Treatment (Radiolabeled Monoclonal Antibody Therapy)
Arm/Group 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. rituximab: Given IV yttrium Y 90 ibritumomab tiuxetan: Given IV indium In 111 ibritumomab tiuxetan: Given IV oprelvekin: Given subcutaneously filgrastim: Given subcutaneously
Measure Participants	0

6. Secondary Outcome

Title	Appearance of Tumor and Normal Organ Images on the Second In2B8 Scan (Phase I)
Description	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.
Time Frame	At week 12

Outcome Measure Data

Analysis Population Description

Not collected. Study team decision not to analyze this endpoint.

Arm/Group Title	Treatment (Radiolabeled Monoclonal Antibody Therapy)
Arm/Group 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. rituximab: Given IV yttrium Y 90 ibritumomab tiuxetan: Given IV indium In 111 ibritumomab tiuxetan: Given IV oprelvekin: Given subcutaneously filgrastim: Given subcutaneously
Measure Participants	0

7. Secondary Outcome

Title	Survival (Phase II)
Description	Estimated using the method of Kaplan-Meier.
Time Frame	From registration to death due to any cause, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

Phase II portion of the study. One patient out of the 39 was deemed ineligible and was not included in survival analysis.

Arm/Group Title	Treatment : Dose Level 6
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Measure Participants	38
Median (95% Confidence Interval) [years]	NA

8. Secondary Outcome

Title	Time to Disease Progression (Phase II)
Description	Estimated using the method of Kaplan-Meier.
Time Frame	From registration to the earliest date documentation of>disease progression, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

All eligible phase II patients. One out of the 39 phase II patients was deemed ineligible.

Arm/Group Title	Treatment : Dose Level 6
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Measure Participants	38
Median (95% Confidence Interval) [years]	2

9. Secondary Outcome

Title	Tumor Response Rate (Phase II)
Description	Calculated by the number of tumor responses divided by the total number of evaluable patients. An exact binomial confidence interval will be calculated.
Time Frame	Assessed up to 5 years

Outcome Measure Data

Analysis Population Description

All eligible phase II patients. One of the 39 phase II patients was deemed ineligible

Arm/Group Title	Treatment : Dose Level 6
Arm/Group Description	Patients receive: Cycle 1: 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8 Cycle 2 (Cycle 2 delivered 24-36 weeks after Cycle 1): 250 mg/m^2 rituximab IV on days 1 and 8, 2 mg (5.0mCi of In-111) Indium (In-111 ibritumomab tiuxetan) IV over 10 minutes on day 1, 0.4 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8. Patients also receive: 480 mcg filgrastim (G-CSF) subcutaneously (SC) daily when ANC is less than 1500. 50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
Measure Participants	38
Number (95% Confidence Interval) [percentage of patients with response]	89.5

Adverse Events

Time Frame	Baseline to 30 days post treatment, up to 3 years
Adverse Event Reporting Description	Some of the observed Adverse Events were collected without regard to the specific Adverse Event Term, but as a general adverse event within an organ system class. These events are noted with the inclusion of "Other, specify" in the term.
Arm/Group Title	Treatment: Trial 1, Dose Level 1		Treatment: Trial 1, Dose Level 2		Treatment: Trial 2, Dose Level 3		Treatment: Trial 2, Dose Level 4		Treatment: Trial 3, Dose Level 5		Treatment: Trial 3, Dose Level 6		Treatment : Phase II (Dose Level 6)
Arm/Group Description	0.2 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8		0.3 mCi/kg Yttrium (Y-90 ibritumomab tiuxetan (IDEC-90Y2B8) IV over 10 minutes on day 8		50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.		50 micrograms/kg Interleukin-11 SC when PLT counts less than 75,000.		50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.		50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.		50 micrograms/kg Interleukin-11 SC when PLT counts less than 150,000.
All Cause Mortality
	Treatment: Trial 1, Dose Level 1		Treatment: Trial 1, Dose Level 2		Treatment: Trial 2, Dose Level 3		Treatment: Trial 2, Dose Level 4		Treatment: Trial 3, Dose Level 5		Treatment: Trial 3, Dose Level 6		Treatment : Phase II (Dose Level 6)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment: Trial 1, Dose Level 1		Treatment: Trial 1, Dose Level 2		Treatment: Trial 2, Dose Level 3		Treatment: Trial 2, Dose Level 4		Treatment: Trial 3, Dose Level 5		Treatment: Trial 3, Dose Level 6		Treatment : Phase II (Dose Level 6)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/11 (36.4%)		5/7 (71.4%)		4/9 (44.4%)		2/4 (50%)		1/5 (20%)		1/6 (16.7%)		6/39 (15.4%)
Blood and lymphatic system disorders
Anemia	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	2/4 (50%)	9	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Blood and lymphatic system disorders - Other, specify	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	12	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Cardiac disorders
Supraventricular tachycardia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/11 (9.1%)	3	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Diarrhea	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
General disorders
Fatigue	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
General disorders and administration site conditions - Other, specify	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Pain	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	6	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Infections and infestations
Infections and infestations - Other, specify	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	9	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Wound infection	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Investigations
Neutrophil count decreased	1/11 (9.1%)	3	4/7 (57.1%)	21	2/9 (22.2%)	6	0/4 (0%)	0	1/5 (20%)	3	1/6 (16.7%)	3	5/39 (12.8%)	18
Platelet count decreased	0/11 (0%)	0	2/7 (28.6%)	12	2/9 (22.2%)	6	2/4 (50%)	9	0/5 (0%)	0	1/6 (16.7%)	6	3/39 (7.7%)	15
White blood cell decreased	0/11 (0%)	0	1/7 (14.3%)	6	1/9 (11.1%)	3	0/4 (0%)	0	1/5 (20%)	3	1/6 (16.7%)	3	3/39 (7.7%)	12
Metabolism and nutrition disorders
Dehydration	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Psychiatric disorders
Confusion	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	6	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Renal and urinary disorders
Renal and urinary disorders - Other, specify	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Reproductive system and breast disorders
Vaginal hemorrhage	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/11 (9.1%)	6	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Skin and subcutaneous tissue disorders
Erythema multiforme	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Urticaria	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Vascular disorders
Hypotension	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Thromboembolic event	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Other (Not Including Serious) Adverse Events
	Treatment: Trial 1, Dose Level 1		Treatment: Trial 1, Dose Level 2		Treatment: Trial 2, Dose Level 3		Treatment: Trial 2, Dose Level 4		Treatment: Trial 3, Dose Level 5		Treatment: Trial 3, Dose Level 6		Treatment : Phase II (Dose Level 6)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		7/7 (100%)		9/9 (100%)		4/4 (100%)		5/5 (100%)		6/6 (100%)		39/39 (100%)
Blood and lymphatic system disorders
Anemia	10/11 (90.9%)	93	7/7 (100%)	90	9/9 (100%)	57	3/4 (75%)	51	5/5 (100%)	33	6/6 (100%)	72	34/39 (87.2%)	330
Blood and lymphatic system disorders - Other, specify	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	18	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Febrile neutropenia	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Cardiac disorders
Atrial flutter	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Cardiac disorders - Other, specify	1/11 (9.1%)	9	0/7 (0%)	0	4/9 (44.4%)	12	3/4 (75%)	15	4/5 (80%)	12	2/6 (33.3%)	18	9/39 (23.1%)	33
Sinus tachycardia	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Supraventricular tachycardia	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Ear and labyrinth disorders
Ear pain	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Endocrine disorders
Endocrine disorders - Other, specify	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	6	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Eye disorders
Blurred vision	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	6	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
Conjunctivitis	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Dry eye	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Extraocular muscle paresis	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Flashing lights	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Keratitis	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	0/39 (0%)	0
Watering eyes	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	0/39 (0%)	0
Gastrointestinal disorders
Abdominal pain	3/11 (27.3%)	15	1/7 (14.3%)	3	2/9 (22.2%)	9	1/4 (25%)	3	2/5 (40%)	9	0/6 (0%)	0	5/39 (12.8%)	18
Bloating	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Constipation	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Diarrhea	1/11 (9.1%)	6	1/7 (14.3%)	3	2/9 (22.2%)	9	0/4 (0%)	0	1/5 (20%)	6	0/6 (0%)	0	6/39 (15.4%)	18
Dry mouth	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Duodenal obstruction	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Dyspepsia	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Esophagitis	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	0/39 (0%)	0
Flatulence	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	2/39 (5.1%)	6
Gastrointestinal disorders - Other, specify	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Mucositis oral	2/11 (18.2%)	6	1/7 (14.3%)	3	2/9 (22.2%)	6	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	3/39 (7.7%)	9
Nausea	2/11 (18.2%)	18	5/7 (71.4%)	21	3/9 (33.3%)	9	2/4 (50%)	6	3/5 (60%)	12	2/6 (33.3%)	6	13/39 (33.3%)	48
Vomiting	0/11 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	6	0/4 (0%)	0	1/5 (20%)	3	1/6 (16.7%)	3	2/39 (5.1%)	6
General disorders
Chills	2/11 (18.2%)	6	0/7 (0%)	0	1/9 (11.1%)	3	1/4 (25%)	3	1/5 (20%)	6	1/6 (16.7%)	9	6/39 (15.4%)	18
Edema limbs	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Fatigue	2/11 (18.2%)	9	5/7 (71.4%)	18	4/9 (44.4%)	15	1/4 (25%)	3	2/5 (40%)	12	4/6 (66.7%)	18	21/39 (53.8%)	84
Fever	1/11 (9.1%)	3	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	2/5 (40%)	6	1/6 (16.7%)	3	1/39 (2.6%)	3
General disorders and administration site conditions - Other, specify	2/11 (18.2%)	6	1/7 (14.3%)	3	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Injection site reaction	0/11 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	6	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	2/39 (5.1%)	6
Non-cardiac chest pain	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	5/39 (12.8%)	15
Pain	0/11 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	6	1/4 (25%)	3	1/5 (20%)	3	1/6 (16.7%)	3	2/39 (5.1%)	6
Immune system disorders
Allergic reaction	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	9	2/6 (33.3%)	6	6/39 (15.4%)	21
Immune system disorders - Other, specify	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
Infections and infestations
Bladder infection	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Infections and infestations - Other, specify	6/11 (54.5%)	18	1/7 (14.3%)	3	3/9 (33.3%)	12	0/4 (0%)	0	2/5 (40%)	12	3/6 (50%)	9	11/39 (28.2%)	36
Skin infection	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	2/39 (5.1%)	6
Wound infection	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	0/39 (0%)	0
Injury, poisoning and procedural complications
Bruising	0/11 (0%)	0	2/7 (28.6%)	6	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Fracture	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Investigations
Alkaline phosphatase increased	3/11 (27.3%)	18	1/7 (14.3%)	6	2/9 (22.2%)	9	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	4/39 (10.3%)	15
Aspartate aminotransferase increased	2/11 (18.2%)	12	3/7 (42.9%)	12	1/9 (11.1%)	6	0/4 (0%)	0	0/5 (0%)	0	2/6 (33.3%)	9	3/39 (7.7%)	12
Blood bilirubin increased	1/11 (9.1%)	3	1/7 (14.3%)	3	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	1/6 (16.7%)	3	3/39 (7.7%)	15
Cholesterol high	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Creatinine increased	0/11 (0%)	0	2/7 (28.6%)	9	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Lymphocyte count decreased	0/11 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	12	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Neutrophil count decreased	9/11 (81.8%)	93	6/7 (85.7%)	141	9/9 (100%)	147	3/4 (75%)	105	5/5 (100%)	60	6/6 (100%)	102	32/39 (82.1%)	477
Platelet count decreased	10/11 (90.9%)	129	7/7 (100%)	117	8/9 (88.9%)	102	4/4 (100%)	84	5/5 (100%)	93	6/6 (100%)	126	39/39 (100%)	711
Weight gain	2/11 (18.2%)	6	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Weight loss	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
White blood cell decreased	11/11 (100%)	135	7/7 (100%)	192	9/9 (100%)	180	3/4 (75%)	123	5/5 (100%)	72	6/6 (100%)	93	34/39 (87.2%)	675
Metabolism and nutrition disorders
Anorexia	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	5/39 (12.8%)	21
Dehydration	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hypercalcemia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	2/39 (5.1%)	6
Hyperglycemia	8/11 (72.7%)	33	3/7 (42.9%)	12	4/9 (44.4%)	30	2/4 (50%)	9	1/5 (20%)	6	5/6 (83.3%)	18	9/39 (23.1%)	30
Hyperkalemia	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hyperuricemia	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hypocalcemia	0/11 (0%)	0	1/7 (14.3%)	6	1/9 (11.1%)	3	1/4 (25%)	6	0/5 (0%)	0	2/6 (33.3%)	6	5/39 (12.8%)	15
Hypoglycemia	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hypokalemia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hypophosphatemia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	15	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/11 (18.2%)	6	1/7 (14.3%)	3	3/9 (33.3%)	12	1/4 (25%)	6	1/5 (20%)	3	3/6 (50%)	12	10/39 (25.6%)	33
Arthritis	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Bone pain	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	2/5 (40%)	6	0/6 (0%)	0	4/39 (10.3%)	12
Myalgia	1/11 (9.1%)	3	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	2/5 (40%)	6	3/6 (50%)	18	9/39 (23.1%)	30
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Nervous system disorders
Dizziness	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	3	2/6 (33.3%)	6	0/39 (0%)	0
Dysgeusia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	0/39 (0%)	0
Extrapyramidal disorder	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
Headache	0/11 (0%)	0	1/7 (14.3%)	6	2/9 (22.2%)	6	1/4 (25%)	3	1/5 (20%)	3	1/6 (16.7%)	3	8/39 (20.5%)	27
Neuralgia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	1/39 (2.6%)	3
Peripheral sensory neuropathy	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	4/39 (10.3%)	12
Psychiatric disorders
Depression	0/11 (0%)	0	2/7 (28.6%)	6	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Insomnia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
Renal and urinary disorders
Urinary frequency	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Urinary incontinence	1/11 (9.1%)	6	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Urinary tract pain	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Reproductive system and breast disorders
Erectile dysfunction	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Gynecomastia	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	6	0/5 (0%)	0	0/6 (0%)	0	2/39 (5.1%)	6
Irregular menstruation	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	3/39 (7.7%)	12
Cough	2/11 (18.2%)	9	1/7 (14.3%)	3	0/9 (0%)	0	1/4 (25%)	3	2/5 (40%)	6	3/6 (50%)	9	4/39 (10.3%)	12
Dyspnea	0/11 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	6	0/4 (0%)	0	1/5 (20%)	3	2/6 (33.3%)	6	2/39 (5.1%)	6
Epistaxis	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	0/39 (0%)	0
Pleural effusion	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Pleuritic pain	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Pneumonitis	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Respiratory, thoracic and mediastinal disorders - Other, specify	1/11 (9.1%)	3	1/7 (14.3%)	6	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Voice alteration	0/11 (0%)	0	2/7 (28.6%)	6	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Skin and subcutaneous tissue disorders
Alopecia	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Dry skin	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Erythema multiforme	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hyperhidrosis	0/11 (0%)	0	1/7 (14.3%)	3	0/9 (0%)	0	0/4 (0%)	0	1/5 (20%)	6	0/6 (0%)	0	2/39 (5.1%)	6
Pruritus	1/11 (9.1%)	3	0/7 (0%)	0	2/9 (22.2%)	6	2/4 (50%)	6	0/5 (0%)	0	0/6 (0%)	0	6/39 (15.4%)	24
Purpura	0/11 (0%)	0	0/7 (0%)	0	2/9 (22.2%)	6	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	3	3/39 (7.7%)	9
Rash maculo-papular	2/11 (18.2%)	6	0/7 (0%)	0	3/9 (33.3%)	12	2/4 (50%)	6	1/5 (20%)	3	1/6 (16.7%)	3	5/39 (12.8%)	15
Skin and subcutaneous tissue disorders - Other, specify	1/11 (9.1%)	6	1/7 (14.3%)	3	1/9 (11.1%)	3	1/4 (25%)	12	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
Urticaria	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	1/6 (16.7%)	3	2/39 (5.1%)	9
Vascular disorders
Flushing	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Hot flashes	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Hypertension	1/11 (9.1%)	3	0/7 (0%)	0	0/9 (0%)	0	1/4 (25%)	3	0/5 (0%)	0	0/6 (0%)	0	0/39 (0%)	0
Phlebitis	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3
Thromboembolic event	0/11 (0%)	0	0/7 (0%)	0	1/9 (11.1%)	3	0/4 (0%)	0	1/5 (20%)	3	0/6 (0%)	0	0/39 (0%)	0
Vascular disorders - Other, specify	0/11 (0%)	0	0/7 (0%)	0	0/9 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/39 (2.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.