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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose of bortezomib

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Thomas C. Shea, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

LCCC 0525

NCT ID:

NCT00334438

Start Date:

July 2006

Completion Date:

October 2011

Related Keywords:

  • Lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent small lymphocytic lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Mantle-Cell

Name

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601