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
  Purpose

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.


Condition Intervention Phase
Lymphoma
Mantle Cell Lymphoma
Indolent Lymphoma
SLL
Drug: rituximab
Drug: bortezomib
Drug: cladribine
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Progression-free survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 39
Study Start Date: July 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00980395

Contacts
Contact: Ruth Cañamar, BA 520-626-6515 rcanamar@azcc.arizona.edu
Contact: Ellen Chase, BS 520-626-6786 echase@azcc.arizona.edu

Locations
United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724-5024
Contact: Clinical Trials Office - Arizona Cancer Center at University o    520-626-9008      
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Thomas P. Miller, MD University of Arizona
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00980395     History of Changes
Other Study ID Numbers: 08-1071-04, P30CA023074, UARIZ-08-1071-04, X05260, CDR0000655078
Study First Received: September 18, 2009
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
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
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
nodal marginal zone B Cell lymphoma
splenic marginal zone lymphoma
Waldenstrom macroglobulinemia
extranodal marginal zone BCL mucosaassoc lymphoid tissue

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bortezomib
Cladribine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 18, 2014