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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00980395
First received: September 18, 2009
Last updated: April 13, 2016
Last verified: April 2016

September 18, 2009
April 13, 2016
July 2009
September 2014   (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.
    Other Name: Leustatin
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.
 
Active, not recruiting
39
December 2021
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Voluntary consent before performance of any study-related procedure
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.
  • Biopsy-proven mantle cell, marginal zone, lymphoplasmacytic, small lymphocytic lymphoma, or follicular lymphoma
  • CD20-positive disease
  • Patients with marginal zone, lymphoplasmacytic, small lymphocytic, or follicular lymphoma - at least one criterion for initiation of treatment must be met:

    • Symptomatic disease
    • Cytopenia related to lymphoma
    • Leukemic phase (> 5,000 malignant lymphocytes/µl)
    • Mass over 5 cm in greatest diameter
    • For lymphoplasmacytic lymphoma: additional treatment criteria are serum viscosity ≥ 4 cp, serum monoclonal protein > 5 g/L, concurrent primary systemic AL amyloidosis, cold agglutinin disease
  • Age over 18
  • Prior treatment with bortezomib and/or rituximab is acceptable
  • For follicular lymphoma only, at least one prior treatment

Exclusion Criteria:

  • Platelet count of < 100 X10 /L within 14 days before enrollment, unless due to bone marrow infiltration with lymphoma, or due to autoimmune thrombocytopenia because of lymphoma.
  • Patient has an absolute neutrophil count of < 1.0 X 10/L within 14 days before registration, unless due to bone marrow infiltration with lymphoma.
  • Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before registration. (Creatinine Clearance is indicated through the Serum Creatinine. If the Serum Creatinine is abnormal, the physician may then due a 24 hour urine to further clarify Creatinine Clearance. A 24 hour urine test is not required per study.)
  • Patient has ≥ Grade 2 peripheral neuropathy within 14 days before registration.
  • Myocardial infarction within 6 months prior to registration or has New York Heart Association (NYHA) Class III or IV heart failure. uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Hypersensitivity to bortezomib, boron or mannitol.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant
  • Patient received other investigational drugs with 14 days before registration
  • Serious medical or psychiatric illness likely to interfere with study participation
  • Diagnosed or treated for another malignancy within 3 years of registration, w/ the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • CNS involvement with lymphoma.
  • Known HIV-positive.
  • History of disease refractory to a purine analog (defined as remission duration of < 6 months to therapy that included fludarabine, pentostatin, or cladribine).
  • History of intolerance of bortezomib, boron, mannitol, cladribine, or rituximab.
  • Patient has > 1.5 X ULN Total Bilirubin
  • Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00980395
08-1071-04, P30CA023074, UARIZ-08-1071-04, X05260, CDR0000655078, 0800001071
Yes
Not Provided
Not Provided
University of Arizona
University of Arizona
National Cancer Institute (NCI)
Principal Investigator: Soham D Puvvada, MD University of Arizona
University of Arizona
April 2016

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