- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00837174
Relapsed and/or Refractory Non-Hodgkin Lymphoma Study (COMBOSTAT)
Phase II Study of Combination Vorinostat and Bortezomib in Patients With Relapsed and/or Refractory Non-Hodgkin Lymphoma
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Fas
- Fas 2
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- 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)
- 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
Exclusion Criteria:
- 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;
- 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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Combination Vorinostat + Bortezomib
Six cycle combination therapy with vorinostat and bortezomib.
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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.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
---|---|
Determine the response rate of this regimen in this patient population.
Tidsram: 6 cycles
|
6 cycles
|
Sekundära resultatmått
Resultatmått |
Tidsram |
---|---|
Determine the progression free survival of this regimen in this patient population.
Tidsram: entire length of study
|
entire length of study
|
Determine the safety and tolerability of this regimen in this patient population.
Tidsram: throughout course of study
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throughout course of study
|
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.
Tidsram: 6 cycles
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6 cycles
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Samarbetspartners och utredare
Utredare
- Huvudutredare: Hector A Preti, M.D., The Methodist Hospital Research Institute
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
- Diffust storcellslymfom
- B-cells lymfom
- Burkitts lymfom
- mantelcellslymfom
- marginalzonens lymfom
- perifert T-cellslymfom
- mycosis fungoides
- litet lymfocytiskt lymfom
- lymfoblastiskt lymfom
- icke-Hodgkin lymfom
- aggressivt lymfom
- indolent lymfom
- T-cellslymfom
- lymfoplasmacytiskt lymfom
- anaplastic large B cell 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
- follicular center cell lymphoma grade 1
- follicular center cell lymphoma grade 2
Ytterligare relevanta MeSH-villkor
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Lymfatiska sjukdomar
- Immunproliferativa störningar
- Lymfom
- Lymfom, icke-Hodgkin
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antineoplastiska medel
- Histon deacetylashämmare
- Bortezomib
- Vorinostat
Andra studie-ID-nummer
- Pro00002085
- 0908-0284 (Annan identifierare: Houston Methodist Research Institute IRB)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
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