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Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University of Arizona
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00980395
First received: September 18, 2009
Last updated: February 6, 2013
Last verified: February 2013

September 18, 2009
February 6, 2013
July 2009
December 2013   (final data collection date for primary outcome measure)
Progression-free survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Progression-free survival at 2 years [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00980395 on ClinicalTrials.gov Archive Site
  • Overall survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Complete response and overall response rate [ Time Frame: After treatment ] [ Designated as safety issue: No ]
  • Long- and short-term toxicity [ Time Frame: During and after treatment ] [ Designated as safety issue: Yes ]
  • Cytokine profiles [ Time Frame: After treatment ] [ Designated as safety issue: No ]
  • Prognostic importance of Aurora kinase A [ Time Frame: After treatment ] [ Designated as safety issue: No ]
  • Prognostic importance of major carcinogenic pathways [ Time Frame: After treatment ] [ Designated as safety issue: No ]
  • Overall survival at 2 years [ Designated as safety issue: No ]
  • Complete response and overall response rate [ Designated as safety issue: No ]
  • Long- and short-term toxicity [ Designated as safety issue: Yes ]
  • Cytokine profiles [ Designated as safety issue: No ]
  • Prognostic importance of Aurora kinase A [ Designated as safety issue: No ]
  • Prognostic importance of major carcinogenic pathways [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma
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

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, 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. Giving bortezomib together with cladribine and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with cladribine and rituximab works in treating patients with advanced mantle cell lymphoma or indolent lymphoma.

OBJECTIVES:

Primary

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

Secondary

  • 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 regimen.
  • 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 regimen.
  • Determine the cytokine profiles for each lymphoma subtype and how they change with this regimen.
  • Evaluate the prognostic importance of major carcinogenic pathways using tissue microarray.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Lymphoma
  • Mantle Cell Lymphoma
  • Indolent Lymphoma
  • SLL
  • Drug: rituximab
    375 mg/m2 IV Day 1. Repeat every 28 days for a maximum of 6 cycles.
    Other Name: Rituxan
  • Drug: bortezomib
    1.3 mg/m2 IV Days 1 and 4. Repeat every 28 days for a maximum of 6 cycles.
    Other Name: Velcade
  • Drug: cladribine
    4 mg/m2 IV over 2 hours Days 1-5. Repeat every 28 days for a maximum of 6 cycles.
Experimental: VCR (Velcade, Cladribine and Rituximab)
  • Rituximab 375 mg/m2 IV day1
  • Cladribine 4 mg/m2 IV over 2 hours days 1-5
  • Bortezomib 1.3 mg/m2 IV days 1 and 4
  • Repeat every 28 days for a maximum of 6 cycles
Interventions:
  • Drug: rituximab
  • Drug: bortezomib
  • Drug: cladribine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
39
December 2013
December 2013   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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 cladribine
  • 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

PATIENT CHARACTERISTICS:

  • 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 participation
  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior bortezomib and/or rituximab allowed
  • More than 14 days since prior investigational agents
  • No other concurrent investigational agents
Both
18 Years and older
No
Contact: Ruth Cañamar, BA 520-626-6515 rcanamar@azcc.arizona.edu
Contact: Ellen Chase, BS 520-626-6786 echase@azcc.arizona.edu
United States
 
NCT00980395
08-1071-04, P30CA023074, UARIZ-08-1071-04, X05260, CDR0000655078
Yes
University of Arizona
University of Arizona
National Cancer Institute (NCI)
Principal Investigator: Thomas P. Miller, MD University of Arizona
University of Arizona
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP