Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate 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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI UNC-LCCC-0525 LCCC 0525, NCT00334438

Objectives

Primary

1. 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.
2. Determine the dose-limiting toxicity of this regimen in these patients.

Secondary

1. Determine the response rate in patients treated with this regimen.

Entry 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

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

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Platelet count ≥ 100,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• 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

Expected Enrollment

Outcomes

Maximum tolerated dose of bortezomib
Dose-limiting toxicity

Response rate

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.

Trial Contact Information

Trial Lead Organizations

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

Thomas Shea, MD, Principal investigator		Ph: 919-966-7746 Email: sheaT@med.unc.edu

Registry Information
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
Trial Start Date		2006-07-01
Registered in ClinicalTrials.gov		NCT00334438
Date Submitted to PDQ		2007-05-04
Information Last Verified		2009-01-06
NCI Grant/Contract Number		CA16086

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