Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma
This study is currently recruiting participants.
Verified February 2013 by University of Arizona
Sponsor:
University of Arizona
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
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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)
|
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
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 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 |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Rituximab Bortezomib |
Cladribine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013