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

NCT ID: NCT00334438

Last Updated: 2016-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-31

Study Completion Date

2011-10-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Keywords

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recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent small lymphocytic lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Zevalin + Velcade Single Arm Study

Zevalin (Ibritumomab Tiuxetan) and Velcade (Bortezomib)

Group Type OTHER

rituximab

Intervention Type BIOLOGICAL

250mg/m2, IV, Days 1 and 8

bortezomib

Intervention Type DRUG

dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15

yttrium Y 90 ibritumomab tiuxetan

Intervention Type RADIATION

Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8

Indium 111 ibritumomab tiuxetan

Intervention Type RADIATION

5cmCi; IV day 1

Interventions

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rituximab

250mg/m2, IV, Days 1 and 8

Intervention Type BIOLOGICAL

bortezomib

dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15

Intervention Type DRUG

yttrium Y 90 ibritumomab tiuxetan

Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8

Intervention Type RADIATION

Indium 111 ibritumomab tiuxetan

5cmCi; IV day 1

Intervention Type RADIATION

Other Intervention Names

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Rituxan Velcade

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas C. Shea, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

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Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

Countries

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United States

Other Identifiers

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CDR0000550130

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 0525

Identifier Type: -

Identifier Source: org_study_id