Recurrent Mantle Cell LymphomaPhase 2NCT00703664
Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma
A Phase 2 study testing Bortezomib, Laboratory Biomarker Analysis and Vorinostat in people with Recurrent Mantle Cell Lymphoma and Recurrent Non-Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 12 sites in United States.
Trial summary
This phase II trial studies how well bortezomib and vorinostat work in treating patients with recurrent mantle cell lymphoma or recurrent and/or refractory diffuse large B-cell lymphoma. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Mantle Cell Lymphoma, Recurrent Non-Hodgkin Lymphoma
- What is being tested?
- Bortezomib, Laboratory Biomarker Analysis and Vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 12 sitesUnited States
- Study dates
- 9 Jul 2008to 1 Dec 2017
- 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
- Histologically confirmed mantle cell or diffuse large B-cell lymphoma; histological material must be available for central pathological review; unstained histological material -- slides or blocks -- must be available for correlative studies; archived material from previous biopsies is acceptable, unless a patient's lymphoma has been known to undergo histological transformation in the past, in which case a repeat biopsy to confirm histology prior to enrollment is required; availability of material must be confirmed at the time of registration, but material may be submitted subsequent to registration and initiation of study treatment
- Measurable disease according to the Revised Response Criteria for Malignant Lymphoma; this requires at least one lesion greater than 1.0 cm in diameter in both the long and short axis as measured by spiral computed tomography (CT) scan or physical exam
- Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
- >= 6 months have elapsed since allogeneic transplant
- No graft vs. host disease (GVHD) is present
- Not currently on immunosuppressive therapy
Show all 26Show fewer
- Prior therapy:
- Mantle cell lymphoma:
- Previously treated or untreated
- No prior bortezomib
- Diffuse large B-cell lymphoma:
- At least one prior systemic therapy
- No prior bortezomib
- Note: Not intended for patients in first relapse who are candidates for high dose therapy with stem cell support
- Life expectancy of greater than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Able to tolerate loperamide or other anti-diarrheal medications
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 75 x 10^9/L
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits or calculated creatinine clearance >= 60 mL/min according to the Cockcroft-Gault formula
- For patients with known human immunodeficiency virus (HIV) infection, a cluster of differentiation (CD)4 count >= 0.5 x 10^9/L
- For patients whose last treatment included bendamustine or fludarabine, a CD4 count >= 0.4 x 10^9/L
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and to report pregnancy or suspected pregnancy while participating in the study
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Chemotherapy or large field radiotherapy within 3 weeks prior to entering the study
- Prior histone deacetylase inhibitor as cancer treatment
- Concurrent treatment with other investigational agents
- Plans for other concurrent cancer treatment; if steroids for cancer control have been used, patients must be off these agents for >= 1 week before starting treatment; exception: maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose < 10 mg/day is permitted
- History of brain metastasis including leptomeningeal metastasis
- Grade >= 2 neuropathy, regardless of cause
Show all 12Show fewer
- Unable to take oral medications
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib or vorinostat
- Not sufficiently recovered from previous treatment
- Medical or other condition (for example: uncontrolled infection; potentially life threatening changes on electrocardiogram [EKG]) or concurrent treatment (for example, marrow suppressive agents such as zidovudine) that represents an inappropriate risk to the patient or likely would compromise achievement of the primary study objective; patients should be closely monitored when given bortezomib in combination with the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and inducers
- Pregnant women are excluded from this study; breastfeeding should be discontinued
- Active concurrent malignancy, except adequately treated non-melanoma skin cancer
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Weill Medical College of Cornell University
New York, New York, 10065
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Moffitt Cancer Center
Tampa, Florida, 33612
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
About this study
Official title: Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
This phase II trial studies how well bortezomib and vorinostat work in treating patients with recurrent mantle cell lymphoma or recurrent and/or refractory diffuse large B-cell lymphoma. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
This was a multicenter, non-randomized phase 2 trial using a Simon two-stage design with 3 cohorts.
PRIMARY OBJECTIVES:
- Estimate the response rates of mantle cell and diffuse large B-cell lymphomas to bortezomib and vorinostat combination therapy.
SECONDARY OBJECTIVES:
- Assess the safety and tolerability of the study regimen. II. Observe progression-free survival and response durations. III. Observe the relationship between pretreatment lymphoma cell nuclear v-rel reticuloendotheliosis viral oncogene homolog A (relA) and response.
OUTLINE:
Patients receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Patients also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
- Being tested
- Bortezomib, Laboratory Biomarker Analysis, Vorinostat
- Medical subject headings
- Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341
Bortezomib: 1.3 mg/m^2/d IV days 1, 4, 8, and 11.
Laboratory Biomarker AnalysisOther
Correlative studies
VorinostatDrug
Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid
Vorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12.
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vorinostat, bortezomib) | Experimental | Participants receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Participants also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Vorinostat precedes bortezomib on days of concurrent administration. Courses repeat every 3 weeks in the absence of disease progression - or unacceptable toxicity. After completion of study therapy, participants are followed periodically.
Treatment arm consists of 3 cohorts, all receiving the same treatment:
A: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
B: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
C: Diffuse Large B-Cell Lymphoma (DLBCL) - with no prior bortezomib. Receives: Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR: Complete Response (CR) + Partial Response (PR) assessed according to the Revised Response Criteria for Malignant Lymphoma.
Measured: Up to 9 years
Secondary outcomes (4)
Best Response
Number of participants per category: Partial Response (PR), Stable Disease (SD), Progressive Disease (PD). PR: Regression of measurable disease and no new sites. SD: Failure to attain Complete Response (CR), /PR or PD. Relapsed or Progressive Disease: Any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Measured: Up to 9 years
Progression-free Survival (PFS)
Median progression-free survival in months per cohort.
Measured: Up to 9 years
Duration of Partial Response
Median duration of response per cohort.
Measured: Up to 9 years
Duration of Stable Disease
Median duration of stable disease per cohort.
Measured: Up to 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2008 (estimated)
- Study start9 Jul 2008
- Primary completion1 Dec 2017
- Study completion1 Dec 2017
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.
- Other trials for Recurrent Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Beata Holkova, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00703664
- Sponsor's protocol ID
- NCI-2009-00275
- Other IDs
- NCI-2009-00275, CDR0000598308, MCC-15428, 8064, N01CM00071, N01CM00100, N01CM62201, N01CM62204
- Status last verified
- Jul 2018
- First submitted
- 20 Jun 2008
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
- ClinicalTrials.gov ID
- NCT00703664
- Acronym / sponsor ID
- NCI-2009-00275
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 9 Jul 2008 (actual)
- Primary completion
- 1 Dec 2017 (actual)
- Study completion
- 1 Dec 2017 (actual)
- First posted
- 23 Jun 2008 (estimated)
- Results
- Posted 7 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well bortezomib and vorinostat work in treating patients with recurrent mantle cell lymphoma or recurrent and/or refractory diffuse large B-cell lymphoma. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
This was a multicenter, non-randomized phase 2 trial using a Simon two-stage design with 3 cohorts.
PRIMARY OBJECTIVES:
- Estimate the response rates of mantle cell and diffuse large B-cell lymphomas to bortezomib and vorinostat combination therapy.
SECONDARY OBJECTIVES:
- Assess the safety and tolerability of the study regimen. II. Observe progression-free survival and response durations. III. Observe the relationship between pretreatment lymphoma cell nuclear v-rel reticuloendotheliosis viral oncogene homolog A (relA) and response.
OUTLINE:
Patients receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Patients also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (vorinostat, bortezomib) | Experimental | Drug: Bortezomib, Other: Laboratory Biomarker Analysis, Drug: VorinostatParticipants receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Participants also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Vorinostat precedes bortezomib on days of concurrent administration. Courses repeat every 3 weeks in the absence of disease progression - or unacceptable toxicity. After completion of study therapy, participants are followed periodically. Treatment arm consists of 3 cohorts, all receiving the same treatment: A: Mantle Cell Lymphoma (MCL) - with no prior bortezomib. B: Mantle Cell Lymphoma (MCL) - with no prior bortezomib. C: Diffuse Large B-Cell Lymphoma (DLBCL) - with no prior bortezomib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologically confirmed mantle cell or diffuse large B-cell lymphoma; histological material must be available for central pathological review; unstained histological material -- slides or blocks -- must be available for correlative studies; archived material from previous biopsies is acceptable, unless a patient's lymphoma has been known to undergo histological transformation in the past, in which case a repeat biopsy to confirm histology prior to enrollment is required; availability of material must be confirmed at the time of registration, but material may be submitted subsequent to registration and initiation of study treatment
- Measurable disease according to the Revised Response Criteria for Malignant Lymphoma; this requires at least one lesion greater than 1.0 cm in diameter in both the long and short axis as measured by spiral computed tomography (CT) scan or physical exam
- Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
- Prior therapy:
- Life expectancy of greater than 3 months
Key exclusion criteria (12 listed)
- Chemotherapy or large field radiotherapy within 3 weeks prior to entering the study
- Prior histone deacetylase inhibitor as cancer treatment
- Concurrent treatment with other investigational agents
- Plans for other concurrent cancer treatment; if steroids for cancer control have been used, patients must be off these agents for >= 1 week before starting treatment; exception: maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose < 10 mg/day is permitted
- History of brain metastasis including leptomeningeal metastasis
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 |
|---|---|---|
| BortezomibAlso: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341Bortezomib: 1.3 mg/m^2/d IV days 1, 4, 8, and 11. | Drug | Treatment (vorinostat, bortezomib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (vorinostat, bortezomib) |
| VorinostatAlso: L-001079038, MSK-390, SAHA, Suberanilohydroxamic AcidVorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12. | Drug | Treatment (vorinostat, bortezomib) |
Primary outcome
Overall Response Rate (ORR)
Time frame: Up to 9 years
ORR: Complete Response (CR) + Partial Response (PR) assessed according to the Revised Response Criteria for Malignant Lymphoma.
4 secondary outcomes
Best Response
Time frame: Up to 9 years
Progression-free Survival (PFS)
Time frame: Up to 9 years
Duration of Partial Response
Time frame: Up to 9 years
Duration of Stable Disease
Time frame: Up to 9 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Recurrent Mantle Cell Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer
RecruitingPhase 2
Testing the Anti-cancer Drug, Glofitamab, in Patients With Mantle Cell Lymphoma (A Type of Blood Cancer) Whose Disease Returned After CAR-T Cell Therapy
Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma
RecruitingPhase 2
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
RecruitingPhase 1
Phase Ib Clinical Study of Keynatinib
Lymphoma, B-Cell
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
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.
Beata Holkova principal investigator
Massey Cancer Center
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Laboratory Biomarker Analysis and Vorinostat in people with Recurrent Mantle Cell Lymphoma and Recurrent Non-Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 12 sites 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 26 inclusion and 12 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 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites 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 7 Aug 2018). 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?
Overall Response Rate (ORR) (time frame: Up to 9 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2018.