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

Condition(s) targeted: Lymphoma

Intervention: bortezomib (Drug); rituximab (Drug); yttrium Y 90 ibritumomab tiuxetan (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: UNC Lineberger Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Thomas C. Shea, MD, Principal Investigator, Affiliation: UNC Lineberger Comprehensive Cancer Center

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.

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 design: Treatment, Non-Randomized, Open Label

Primary outcome:

Maximum tolerated dose of bortezomib

Dose-limiting toxicity

Secondary outcome: Response rate

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States; Recruiting
Clinical Trials Office - Hackensack University Medical Center, Phone: 201-996-2879

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States; Recruiting
Clinical Trials Office - Lineberger Comprehensive Cancer Cente, Phone: 877-668-0683; 919-966-4432

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2006
Last updated: July 29, 2008