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:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00980395
First received: September 18, 2009
Last updated: December 4, 2014
Last verified: December 2014
  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 2015
Estimated Primary Completion Date: December 2015 (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.
Other Name: Leustatin

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

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.
  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

Locations
United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85724-5024
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Soham D Puvvada, 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, 0800001071
Study First Received: September 18, 2009
Last Updated: December 4, 2014
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
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 mucosa assoc lymphoid tissue
nodal marginal zone B Cell lymphoma
splenic marginal zone lymphoma

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

ClinicalTrials.gov processed this record on July 01, 2015