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A Phase II, Open-Label Study of Bortezomib (Velcade), Cladribine and Rituximab (VCR) in Advanced, Newly Diagnosed and Relapsed/Refractory Mantle Cell and Indolent Lymphomas

Phase 2
18 Years
Open (Enrolling)
Lymphoma, Mantle Cell Lymphoma, Indolent Lymphoma, SLL

Thank you

Trial Information

A Phase II, Open-Label Study of Bortezomib (Velcade), Cladribine and Rituximab (VCR) in Advanced, Newly Diagnosed and Relapsed/Refractory Mantle Cell and Indolent Lymphomas



- Determine the 2-year progression-free survival of patients with advanced mantle cell
lymphoma or indolent lymphoma treated with bortezomib, cladribine, and rituximab.


- Determine the 2-year overall survival of patients treated with this regimen.

- Determine the complete response and overall response rate in patients treated with this

- Describe the long- and short-term toxicity of this regimen in these patients.

- Determine the prognostic importance of Aurora kinase A in patients treated with this

- Determine the cytokine profiles for each lymphoma subtype and how they change with this

- Evaluate the prognostic importance of major carcinogenic pathways using tissue

OUTLINE: Patients receive bortezomib IV on days 1 and 4, cladribine IV over 2 hours on days
1-5, and rituximab IV on day 1. Treatment repeats every 28 days for up to 6 courses in the
absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and after course 1 for cytokine profile studies.
Previously collected tissue samples are obtained for analysis of Aurora kinase A and B,
Ki-67, cyclin D, Bcl-2, phosphor-HisH3, c-Met, and VEGF expression by using tissue
microarray (IHC staining), reverse transcriptase-PCR, and/or western blotting.

After completion of study therapy, patients are followed up every 3 months for 2 years.

Inclusion Criteria


- Biopsy confirmed advanced lymphoma, including any of the following subtypes:

- Mantle cell lymphoma

- Marginal zone lymphoma

- Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia)

- Small lymphocytic lymphoma

- Follicular lymphoma

- Must have received ≥ 1 prior treatment

- Newly diagnosed OR relapsed/refractory disease

- No history of disease refractory to a purine analog, defined as remission
duration of < 6 months with therapy that included fludarabine, pentostatin, or

- CD20-positive disease

- Meets ≥ 1 of the following criteria*:

- Symptomatic disease

- Cytopenia related to lymphoma

- Leukemia phase (malignant lymphocytes > 5,000/μL)

- Mass > 5 cm in greatest diameter

- Patients with lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) must
meet ≥ 1 of the following additional criteria:

- Serum viscosity ≥ 4 cp

- Serum monoclonal protein > 5 g/L

- Concurrent primary systemic AL amyloidosis

- Cold agglutinin disease NOTE: *Patients with mantle cell lymphoma are not
required to meet these criteria.

- No CNS involvement by lymphoma


- ANC ≥ 1,000/mm^3 (unless due to bone marrow infiltration with lymphoma)

- Platelet count ≥ 100,000/mm^3(unless due to bone marrow infiltration with lymphoma or
due to autoimmune thrombocytopenia secondary to lymphoma)

- Creatinine normal OR creatinine clearance ≥ 20 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No peripheral neuropathy ≥ grade 2

- None of the following:

- Myocardial infarction within the past 6 months

- NYHA class III-IV heart failure

- Uncontrolled angina

- Severe uncontrolled ventricular arrhythmias

- Evidence of acute ischemia or active conduction system abnormalities by ECG

- Any ECG abnormality at screening has to be documented by the investigator
as not medically relevant

- No hypersensitivity to bortezomib, boron, or mannitol

- No history of intolerance of bortezomib, cladribine, or rituximab

- No serious medical or psychiatric illness likely to interfere with study

- No diagnosis or treatment of another malignancy within the past 3 years except for
completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an
in situ malignancy, or curatively treated prostate cancer deemed to be low-risk

- No known HIV positivity


- See Disease Characteristics

- Prior bortezomib and/or rituximab allowed

- More than 14 days since prior investigational agents

- No other concurrent investigational agents

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 2 years

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Thomas P. Miller, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Arizona


United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

December 2013

Related Keywords:

  • Lymphoma
  • Mantle Cell Lymphoma
  • Indolent Lymphoma
  • SLL
  • recurrent mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • extranodal marginal zone BCL mucosaassoc lymphoid tissue
  • nodal marginal zone B Cell lymphoma
  • splenic marginal zone lymphoma
  • Lymphoma
  • Lymphoma, Mantle-Cell



University of Arizona Cancer Center Tucson, Arizona  85724