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Bortezomib, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed or Refractory Low-Grade, Follicular, or Mantle Cell Non-Hodgkin's Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
bortezomib
yttrium Y 90 ibritumomab tiuxetan
Indium 111 ibritumomab tiuxetan
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma Bone marrow biopsy required for pretreatment evaluation Unilateral bone marrow biopsy allowed Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping Relapsed or refractory disease as defined by disease progression after initial complete response (CR) or failure to achieve CR No bone marrow involvement ≥ 25% within the past 30 days No pleural effusion or significant ascites No active CNS involvement PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 AST ≤ 2.5 times upper limit of normal (ULN) Total bilirubin ≤ 2.5 times ULN Creatinine clearance ≥ 50 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Hepatitis B surface antigen negative No current infection with hepatitis B virus No HIV positivity No neuropathy or neuropathic pain ≥ grade 2 No history of allergic reaction to boron or mannitol No active serious infection or medical or psychiatric illness that would preclude study therapy No other malignancy within the past 5 years except for the following: Basal cell or squamous cell carcinoma of the skin that has been completely resected In situ malignancy that has been completely resected T1-T2a, N0, M0 prostate cancer treated with a prostatectomy or radiotherapy within the past 2 years with an undetectable PSA level No other condition, including any of the following: Myocardial infarction within the past 6 months New York Heart Association class III-IV heart failure Uncontrolled angina Severe uncontrolled ventricular arrhythmias Electrocardiographic evidence of acute ischemia or active conduction system abnormalities PRIOR CONCURRENT THERAPY: Recovered from all prior therapy More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgical resection of malignancy No limitations on the number of prior therapies More than 4 weeks since prior major surgery More than 14 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF) More than 14 days since prior and no other concurrent investigational agents Concurrent participation in a nontreatment study allowed No prior radioimmunotherapy

Sites / Locations

  • Hackensack University Medical Center Cancer Center
  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Zevalin + Velcade Single Arm Study

Arm Description

Zevalin (Ibritumomab Tiuxetan) and Velcade (Bortezomib)

Outcomes

Primary Outcome Measures

Maximum tolerated dose of bortezomib
Dose-limiting toxicity

Secondary Outcome Measures

Response rate

Full Information

First Posted
June 6, 2006
Last Updated
December 22, 2016
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00334438
Brief Title
Bortezomib, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed or Refractory Low-Grade, Follicular, or Mantle Cell Non-Hodgkin's Lymphoma
Official Title
A Phase I Study Evaluating Combined Zevalin (Ibritumomab Tiuxetan) and Valcade (Bortezomib) in Relapsed/Refractory Low-Grade or Follicular B-Cell and Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, and radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them without harming normal cells. Giving bortezomib together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan in treating patients with relapsed or refractory low-grade, follicular, or mantle cell non-Hodgkin's lymphoma.
Detailed Description
OBJECTIVES: Primary Determine the maximum tolerated dose (MTD) of bortezomib in combination with rituximab and yttrium Y 90 ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma. Determine the dose-limiting toxicity of this regimen in these patients. Secondary Determine the response rate in patients treated with this regimen. OUTLINE: This is a multicenter, open-label, nonrandomized, dose-escalation study of bortezomib. Patients receive rituximab IV over 4 hours followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 to assess biodistribution. Patients without altered biodistribution receive rituximab IV over 4 hours followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients also receive bortezomib IV over 3-5 seconds on days 4, 8, 11, and 15. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients may be treated at the MTD. After completion of study treatment, patients are followed every 3 months for 18 months and then every 6 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zevalin + Velcade Single Arm Study
Arm Type
Other
Arm Description
Zevalin (Ibritumomab Tiuxetan) and Velcade (Bortezomib)
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
250mg/m2, IV, Days 1 and 8
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 ibritumomab tiuxetan
Intervention Description
Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8
Intervention Type
Radiation
Intervention Name(s)
Indium 111 ibritumomab tiuxetan
Intervention Description
5cmCi; IV day 1
Primary Outcome Measure Information:
Title
Maximum tolerated dose of bortezomib
Time Frame
2 years
Title
Dose-limiting toxicity
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Response rate
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma Bone marrow biopsy required for pretreatment evaluation Unilateral bone marrow biopsy allowed Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping Relapsed or refractory disease as defined by disease progression after initial complete response (CR) or failure to achieve CR No bone marrow involvement ≥ 25% within the past 30 days No pleural effusion or significant ascites No active CNS involvement PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 AST ≤ 2.5 times upper limit of normal (ULN) Total bilirubin ≤ 2.5 times ULN Creatinine clearance ≥ 50 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Hepatitis B surface antigen negative No current infection with hepatitis B virus No HIV positivity No neuropathy or neuropathic pain ≥ grade 2 No history of allergic reaction to boron or mannitol No active serious infection or medical or psychiatric illness that would preclude study therapy No other malignancy within the past 5 years except for the following: Basal cell or squamous cell carcinoma of the skin that has been completely resected In situ malignancy that has been completely resected T1-T2a, N0, M0 prostate cancer treated with a prostatectomy or radiotherapy within the past 2 years with an undetectable PSA level No other condition, including any of the following: Myocardial infarction within the past 6 months New York Heart Association class III-IV heart failure Uncontrolled angina Severe uncontrolled ventricular arrhythmias Electrocardiographic evidence of acute ischemia or active conduction system abnormalities PRIOR CONCURRENT THERAPY: Recovered from all prior therapy More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgical resection of malignancy No limitations on the number of prior therapies More than 4 weeks since prior major surgery More than 14 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF) More than 14 days since prior and no other concurrent investigational agents Concurrent participation in a nontreatment study allowed No prior radioimmunotherapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas C. Shea, MD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hackensack University Medical Center Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Bortezomib, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed or Refractory Low-Grade, Follicular, or Mantle Cell Non-Hodgkin's Lymphoma

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