LymphomaPhase 2VCRNCT00980395
Bortezomib, Cladribine, and Rituximab in Treating Patients With Advanced Mantle Cell Lymphoma or Indolent Lymphoma
A Phase 2 study testing rituximab, bortezomib and cladribine in people with Lymphoma and Mantle Cell Lymphoma, run by University of Arizona at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Mantle Cell Lymphoma, Indolent Lymphoma
- What is being tested?
- rituximab, bortezomib and cladribine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jul 2009to 14 Aug 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Arizona Cancer Center
Tucson, Arizona, 85724-5024
About this study
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
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.
Read the 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.
- Conditions
- Lymphoma, Mantle Cell Lymphoma, Indolent Lymphoma, SLL
- Being tested
- rituximab, bortezomib, cladribine
- Keywords
- 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
- Medical subject headings
- Lymphoma, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
Also called Rituxan
375 mg/m2 IV Day 1. Repeat every 28 days for a maximum of 6 cycles.
bortezomibDrug
Also called Velcade
1.3 mg/m2 IV Days 1 and 4. Repeat every 28 days for a maximum of 6 cycles.
cladribineDrug
Also called Leustatin
4 mg/m2 IV over 2 hours Days 1-5. Repeat every 28 days for a maximum of 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| VCR (Velcade, Cladribine and Rituximab) | Experimental | * 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 Receives: Drug: rituximab; Drug: bortezomib; Drug: cladribine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival at 2 Years
PFS was calculated from the first dose of study drug to the first documentation of disease progression, death regardless of cause, or change in therapy due to disease progression, whichever occurred first. If disease progression did not occur by the end of treatment, patients were evaluated every 3 months until progression with physical examination, laboratory studies, and conventional computed tomographic imaging, up to a maximum of 2 years. The Kaplan-Meier product-limit method will be used to estimate progression-free survival in the presence of censoring.
Measured: 2 years
Secondary outcomes (3)
Overall Survival at 2 Years
Measured: 2 years
Complete Response Rate
Measured: Two years
Partial Response
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2009 (estimated)
- Study start7 Jul 2009
- Primary completion12 Sep 2014
- Study completion14 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Daniel O. Persky, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00980395
- Sponsor's protocol ID
- 0800001071
- Other IDs
- P30CA023074, UARIZ-08-1071-04, X05260, CDR0000655078, 0800001071, 08-1071-04
- Acronym
- VCR
- Status last verified
- Dec 2019
- First submitted
- 18 Sep 2009
- Last updated
- 30 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Puvvada SD, Guillen-Rodriguez J, Kumar A, Inclan L, Heard K, Rivera XI, Anwer F, Schatz JH, Mahadevan D, Persky DO. Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas. Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):58-64. doi: 10.1016/j.clml.2017.09.001. Epub 2017 Sep 19.
PubMed 29056470
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00980395
- Acronym / sponsor ID
- VCR / 0800001071
- Conditions
- Lymphoma, Mantle Cell Lymphoma, Indolent Lymphoma, SLL
- Keywords
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Jul 2009 (actual)
- Primary completion
- 12 Sep 2014 (actual)
- Study completion
- 14 Aug 2018 (actual)
- First posted
- 21 Sep 2009 (estimated)
- Results
- Posted 22 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VCR (Velcade, Cladribine and Rituximab) | Experimental | Drug: rituximab, Drug: bortezomib, Drug: cladribine* 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabAlso: Rituxan375 mg/m2 IV Day 1. Repeat every 28 days for a maximum of 6 cycles. | Drug | VCR (Velcade, Cladribine and Rituximab) |
| bortezomibAlso: Velcade1.3 mg/m2 IV Days 1 and 4. Repeat every 28 days for a maximum of 6 cycles. | Drug | VCR (Velcade, Cladribine and Rituximab) |
| cladribineAlso: Leustatin4 mg/m2 IV over 2 hours Days 1-5. Repeat every 28 days for a maximum of 6 cycles. | Drug | VCR (Velcade, Cladribine and Rituximab) |
Primary outcome
Progression-free Survival at 2 Years
Time frame: 2 years
PFS was calculated from the first dose of study drug to the first documentation of disease progression, death regardless of cause, or change in therapy due to disease progression, whichever occurred first. If disease progression did not occur by the end of treatment, patients were evaluated every 3 months until progression with physical examination, laboratory studies, and conventional computed tomographic imaging, up to a maximum of 2 years. The Kaplan-Meier product-limit method will be used to estimate progression-free survival in the presence of censoring.
3 secondary outcomes
Overall Survival at 2 Years
Time frame: 2 years
Complete Response Rate
Time frame: Two years
Partial Response
Time frame: Two years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29056470Puvvada SD, Guillen-Rodriguez J, Kumar A, Inclan L, Heard K, Rivera XI, Anwer F, Schatz JH, Mahadevan D, Persky DO. Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas. Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):58-64. doi: 10.1016/j.clml.2017.09.001. Epub 2017 Sep 19.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel O. Persky, MD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab, bortezomib and cladribine in people with Lymphoma and Mantle Cell Lymphoma, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival at 2 Years (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00980395, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2019.