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Non-Hodgkin LymphomaPhase 2COMBOSTATNCT00837174

Relapsed and/or Refractory Non-Hodgkin Lymphoma Study

A Phase 2 study testing Vorinostat in combination with Bortezomib in people with Non-Hodgkin Lymphoma, run by The Methodist Hospital Research Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to determine the rate of response to the drugs bortezomib (Velcade) and vorinostat (Zolinza), when used in combination, in patients with relapsed (recurrent) and/or refractory (difficult to treat) non-Hodgkin Lymphoma, and to determine the safety and tolerability of this regimen. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Hodgkin Lymphoma
What is being tested?
Vorinostat in combination with Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2010to May 2012
Phase
Phase 2
Are there results?
None posted in the registry

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 non-Hodgkin Lymphoma including small lymphocytic lymphoma, lymphoplasmacytic lymphoma, follicular center cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma, anaplastic large cell lymphoma, nasal NK/T cell lymphoma, mycosis fungoides/Sezary syndrome, angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphomas not otherwise specified
  • Received 2 or > prior therapies, which may include hematopoietic cell transplant (HCT)
  • Received treatment with a nucleoside analog, or an alkylating agent, an anthracycline and/or in the case of B cell lymphomas, rituximab
  • Resistant disease to 2 regimens or resistant disease to at least 1 regimen after first relapse
  • Bi-dimensionally measurable disease documented within 30 days prior to enrollment. Bidimensionally measurable disease is defined as:
  • A lymph node or tumor mass that can be accurately measured in two dimensions by CT,MRI, medical photograph (skin or oral lesion), plain X-ray, PET scan or other conventional technique and a greatest diameter of 1 cm or >; or palpable lesions with both diameters > 2 cm (lesion measured in 2 largest perpendicular dimensions in millimeters)
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  • For the purposes of this protocol, disease should be located in an area of no prior radiation therapy or a clear progression in an area that was previously irradiated
  • Adequate organ and marrow function obtained < or = to 14 days prior to enrollment as defined by a(n):
  • ANC > or = to 1,000/microliter
  • Platelet count > or = to 100,000/microliter, or > or = to 75,000/microliter if the bone marrow is involved
  • Hemoglobin level > or = to 9 g/dL
  • Total bilirubin < or = to 1.5 x institutional upper limit of normality (ULN).(If abnormal, direct bilirubin less than or equal to 1.5 x institutional ULN)
  • ALT or AST < or = to 2.5 x institutional ULN (< or = to 5 x institutional ULN if liver involvement with lymphoma)
  • Serum creatinine < or = to 1.5 x institutional ULN
  • Zubrod (ECOG) Performance Status of 0 or 1
  • Age > than or = to 18 years
  • Life expectancy > or = to 3 months as clinically determined by referring physician
  • Female patient is either post menopausal, free from menses for > 2 years, surgically sterilized or willing to use highly effective methods of contraception (i.e., a condom in conjunction with a diaphragm, or spermicidal jelly; or oral, injectable, or implanted birth control; or abstinence ) to prevent pregnancy throughout the study, starting with visit 1
  • Female patients of childbearing potential must have a negative serum pregnancy test (beta-HCG) within 72 hours of enrollment and should not be nursing due to the potential for congenital abnormalities and of harm to nursing infants due to this treatment regimen
  • Male patient agrees to use an adequate method of contraception (i.e., a condom if female partner uses a diaphragm, spermicidal jelly; or oral, injectable, or implanted birth control; or abstinence) for the duration of the study and for 12 weeks after the last dose
  • Patient must be able to swallow capsules
  • Signed and dated IRB/ethics committee-approved informed consent before any protocol specific screening procedures are performed
  • Both men and women of all races and ethnic groups are eligible for this trial

Who cannot join

  • Prior investigational therapy within 3 weeks of enrollment. Investigational therapy is defined as treatment that is not approved for any indication
  • CNS metastases, as indicated by clinical symptoms,cerebral edema, requirement for corticosteroids and/or progressive growth (treated CNS metastases must be stable for greater than 2 weeks prior to enrollment)
  • Active second malignancy that requires treatment or that would interfere with assessment of response
  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer with < 5 years of documented disease-free status
  • Treatment with the following within the timeframe specified prior to enrollment:
  • Chemotherapy, radiotherapy, immunotherapy (active (such as vaccines) or passive (such as monoclonal antibodies or immunotoxins)) or major surgery < or = to 3 weeks;
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  • Nitrosourea, or mitomycin < or = to 6 weeks
  • Radioimmunotherapy (e.g. Bexxar or Zevalin) < or = to 12 weeks
  • Concurrent enzyme-inducing anticonvulsant agents or valproic acid in last 4 weeks
  • Prior bortezomib or any other proteasome inhibitor
  • Prior vorinostat or any other histone deacetylase inhibitor
  • Concurrent systemic corticosteroids (<10 mg/day of prednisone or equivalent for adrenal insufficiency or acute allergic reactions allowed)
  • Uncontrolled current illness including, but not limited to:
  • Clinically or laboratory determined active infection
  • Clinically limiting congestive heart failure or ejection fraction (EF) <45%
  • Clinically unstable angina pectoris (or myocardial infarction within 6 months of Day 1)
  • Clinically significant cardiac arrhythmia
  • Limiting pulmonary hypertension
  • Pre-existing neuropathy ≥ grade 2
  • Patients with pleural effusions, ascites or peripheral edema grade 2 or >
  • HIV
  • Active viral hepatitis
  • Major surgery or significant traumatic injury within 21 days prior to enrollment (this does not apply to placement of a venous access device)
  • Hypersensitivity to any of the components in vorinostat or bortezomib or agents containing boron or mannitol
  • Significant psychiatric illness/social situations that would limit compliance with study medication and requirements of the study as determined by study MD
  • Significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study

About this study

Official title: Phase II Study of Combination Vorinostat and Bortezomib in Patients With Relapsed and/or Refractory Non-Hodgkin Lymphoma

The purpose of this study is to determine the rate of response to the drugs bortezomib (Velcade) and vorinostat (Zolinza), when used in combination, in patients with relapsed (recurrent) and/or refractory (difficult to treat) non-Hodgkin Lymphoma, and to determine the safety and tolerability of this regimen.

Read the detailed description

More selective and less toxic therapeutic strategies are needed to improve cure rates and prolong survival in patients with relapsed and/or refractory non-Hodgkin Lymphoma.

Amongst the multiple new pathways recently studied two have emerged as potentially important targets for new agents in lymphoma. These include the ubiquitin proteasome pathway and the biochemical reactions that control histone acetylation. The first two agents in each class to have been studied in lymphomas are: bortezomib and vorinostat. Bortezomib has been granted FDA approval for the treatment of mantle cell lymphoma and has established activity in a variety of B-cell lymphomas including follicular, marginal zone and diffuse large B-cell lymphoma. Vorinostat or SAHA (suberoylanilide hydroxamic acid) has been FDA approved for the treatment of refractory cutaneous T-cell lymphomas and has also shown activity in other lymphomas.

Synergistic activity between vorinostat and bortezomib has been observed in different cell lines. The proposed study will be a phase II trial of the combination of vorinostat and bortezomib at the recommended dose-schedule in patients with recurrent and/or refractory lymphomas, indolent and aggressive, and B or T.

Being tested
Vorinostat in combination with Bortezomib
Keywords
non-Hodgkin Lymphoma, aggressive lymphoma, indolent lymphoma, B cell lymphoma, T cell lymphoma, Diffuse large B cell lymphoma, anaplastic large B cell lymphoma, lymphoblastic lymphoma, Burkitt's lymphoma, transformed follicular center cell lymphoma, transformed marginal zone lymphoma, transformed small lymphocytic lymphoma, grade 3 follicular center cell lymphoma, blastic form marginal zone lymphoma, transformed cutaneous T cell lymphoma, mycosis fungoides stage IV, angioimmunoblastic lymphadenopathy-like T-cell lymphoma, nasal NK/T cell lymphoma, peripheral T-cell lymphoma, small lymphocytic lymphoma
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, T-Cell, Lymphoma, Large B-Cell, Diffuse, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Mycosis Fungoides, Lymphoma, T-Cell, Peripheral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vorinostat in combination with BortezomibDrug

    Also called vorinostat (Zolinza), bortezomib (Velcade)

    Patients will be treated with oral vorinostat on days 1 through 14 followed by a 7-day rest period, for a 21-day treatment cycle for up to 6 cycles in the absence of disease progression or unacceptable toxicity. The patients will receive once-daily oral vorinostat (400 mg) with bortezomib 1.3 mg/m2 as an IV push on days 1, 4, 8, 11.

Study groups in NCT00837174
Study groupRoleWhat they receive
Combination Vorinostat + BortezomibExperimentalSix cycle combination therapy with vorinostat and bortezomib.
Receives: Drug: Vorinostat in combination with Bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine the response rate of this regimen in this patient population.

    Measured: 6 cycles

Secondary outcomes (3)

  1. Determine the progression free survival of this regimen in this patient population.

    Measured: entire length of study

  2. Determine the safety and tolerability of this regimen in this patient population.

    Measured: throughout course of study

  3. To correlate response rate and progression free survival with pre-treatment and post-treatment NFkB, TRAIL, cyclin D1, histone acetylation, EBV related proteins, and CTA expression.

    Measured: 6 cycles

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2009 (estimated)
  2. Study startJun 2010
  3. Primary completionMay 2012
  4. Study completionMay 2012

Why it stopped: Study never activated/opened as funding source and other support not available.

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00837174
Sponsor's protocol ID
Pro00002085
Other IDs
0908-0284
Acronym
COMBOSTAT
Status last verified
Sep 2017
First submitted
3 Feb 2009
Last updated
19 Sep 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided: To be determined

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vorinostat in combination with Bortezomib in people with Non-Hodgkin Lymphoma, run by The Methodist Hospital Research Institute.

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 23 inclusion and 26 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: withdrawn, as of the sponsor's last update on 19 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Determine the response rate of this regimen in this patient population. (time frame: 6 cycles). 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 NCT00837174.

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 19 Sep 2017.

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