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

December 22, 2016 updated by: UNC Lineberger Comprehensive Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Zevalin + Velcade Single Arm Study
Zevalin (Ibritumomab Tiuxetan) and Velcade (Bortezomib)
Biological: rituximab
250mg/m2, IV, Days 1 and 8
Other Names:
  • Rituxan
Drug: bortezomib
dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15
Other Names:
  • Velcade
Radiation: yttrium Y 90 ibritumomab tiuxetan
Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8
Radiation: Indium 111 ibritumomab tiuxetan
5cmCi; IV day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of bortezomib
Time Frame: 2 years
2 years
Dose-limiting toxicity
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Response rate
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Thomas C. Shea, MD, UNC Lineberger Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

October 1, 2011

Study Registration Dates

First Submitted

June 6, 2006

First Submitted That Met QC Criteria

June 6, 2006

First Posted (Estimate)

June 7, 2006

Study Record Updates

Last Update Posted (Estimate)

December 23, 2016

Last Update Submitted That Met QC Criteria

December 22, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC 0525
  • CDR0000550130 (Other Identifier: PDQ number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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