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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00334438
• Other study ID #: LCCC 0525
• Secondary ID: CDR0000550130
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2006
• Last updated: December 22, 2016
• Start date: July 2006
• Est. completion date: October 2011

Study information

• Verified date: December 2016
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2011
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Biological:
• rituximab
250mg/m2, IV, Days 1 and 8

Drug:
• bortezomib
dose escalation 1.0, 1.3, or 1.5, IVP; Days 4, 8, 11, 15

Radiation:
• yttrium Y 90 ibritumomab tiuxetan
Dose dependant upon platelet count (0.4mCi/kg) not to exceed 32mCi; Day 8
• Indium 111 ibritumomab tiuxetan
5cmCi; IV day 1

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of bortezomib		2 years	Yes
Primary	Dose-limiting toxicity		8 weeks	Yes
Secondary	Response rate		5 years	No