Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma
Condition: Adult Diffuse Large B-Cell Lymphoma; B-Cell Non-Hodgkin Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin Lymphoma; T-Cell Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell
Intervention: Autologous Hematopoietic Stem Cell Transplantation; Bortezomib; Carmustine; Cytarabine; Etoposide; Melphalan; Rituximab; Vorinostat
Intervention description: Undergo ASCT; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given PO
Intervention MeSH terms: Cytarabine; Rituximab; Antineoplastic Agents, Immunological; Etoposide; Etoposide phosphate; Bortezomib; Melphalan; Mechlorethamine; Vorinostat; Carmustine; Podophyllotoxin; Nitrogen Mustard Compounds; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Autologous stem cell transplant; NHL; maintenance therapy

Summary:

      This phase II trial studies the side effects and how well bortezomib and vorinostat work in
      treating patients with non-Hodgkin lymphoma (NHL) after patients' own stem cell (autologous)
      transplant. Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells
      and make them more likely to die by blocking some of the enzymes needed for cell growth.
      Giving bortezomib together with vorinostat after an autologous stem cell transplant may thus
      kill lymphoma cells that remain after transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  INCLUSION CRITERIA FOR AUTOLOGOUS TRANSPLANT

          -  Diagnosis of non-Hodgkin's lymphoma, transformed B-cell lymphoma, follicular lymphoma,
             mantle cell lymphoma, diffuse large B-cell or T-cell lymphoma, and deemed a candidate
             for autologous transplant

          -  American Heart Association class I: patients with cardiac disease but without
             resulting limitation of physical activity; ordinary physical activity does not cause
             undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients > 60
             years of age must have a left ventricular ejection fraction of at least >= 40%
             demonstrated by multi gated acquisition scan (MUGA) or echocardiogram (Echo)

          -  Total bilirubin =< 1.5 mg/dL

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x the upper
             limit of normal

          -  Creatinine clearance (CrCL) (calculated creatinine clearance is permitted) > 40 mL/min

          -  Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in
             one second (FEV1), and forced vital capacity (FVC) >= 50% of predicted (corrected for
             hemoglobin)

          -  Autologous graft with a minimum of >= 3.0 x 10^6 CD34+ cells/kg; not CD34 selected

          -  Signed informed consent

          -  Female patients of childbearing potential has a negative serum pregnancy test
             beta-human chorionic gonadotropin (hCG)

          -  Female patient is either postmenopausal, free from menses for >= 2 years, surgically
             sterilized, or willing to use 2 adequate barrier methods of contraception to prevent
             pregnancy or agrees to abstain from heterosexual activity throughout the study

          -  Male patient agrees to use an adequate method of contraception for the duration of the
             study

          -  INCLUSION CRITERIA FOR MAINTENANCE THERAPY

          -  30-120 days post ASCT for non-Hodgkin's lymphoma

          -  CrCL >= 40 ml/min

          -  Platelets (PLT) >= 75,000 cells/mm^3 for 5 days after recovery from ASCT nadir

          -  Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 for 5 days after recovery from
             ASCT nadir

          -  Total bilirubin (TB) =< 1.5 x upper limit of normal (ULN)

          -  AST/ALT =< 2.5 x ULN

        Exclusion Criteria:

          -  EXCLUSION CRITERIA FOR AUTOLOGOUS TRANSPLANT

          -  Karnofsky performance score < 70%

          -  Uncontrolled bacterial, viral, or fungal infection (currently taking medication and
             with progression or no clinical improvement)

          -  Pregnant or breastfeeding

          -  Fertile men and women unwilling to use contraceptive techniques from the time of
             transplant until one month post maintenance therapy

          -  Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)

          -  Patients with evidence of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML)
             or abnormal cytogenetics analysis indicative of MDS on the pre-transplant bone marrow
             examination

          -  Prolonged corrected QT interval (QTC) on electrocardiogram (EKG)

          -  Poorly-controlled diabetes mellitus (DM)

          -  >= grade 2 peripheral neuropathy

          -  Prior history of human immunodeficiency virus (HIV) positivity or known history of
             hepatitis B or C

          -  Previous history of hypersensitivity to bortezomib, boron, or mannitol; known
             hypersensitivity to the components of study drug or its analogs

          -  Require therapeutic anticoagulation treatment, especially with Coumadin

          -  Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days
             (42 days for nitrosoureas or mitomycin C) or who has not recovered from adverse events
             due to agents administered more than 30 days earlier

          -  Patient is currently participating or has participated in a study with an
             investigational compound or devise within 30 days of initial dosing with study drug(s)

          -  Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g.,
             romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589,
             MGCD0103, CRA024781, etc); patients who have received compounds with HDAC
             inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not
             enroll in this study; patients who have received such compounds for other indications,
             e.g. valproic acid for epilepsy, may enroll after a 30-day washout period

          -  History of central nervous system (CNS) disease

          -  Symptomatic ascites or pleural effusions

          -  Patient has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Patient is, at the time of signing informed consent, a regular user (including
             "recreational use") of any illicit drugs, substance abuse or had a recent history
             (within the last year) of drug or alcohol abuse

          -  Patient with a history of a prior malignancy with the exception of complete resection
             of basal cell carcinoma or squamous cell carcinoma or an in situ malignancy;
             adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) <
             1.0; or who has undergone potentially curative therapy with no evidence of disease for
             five years, and/or who is deemed at low risk for recurrence by his/her treating
             physician

          -  Patient has a history or current evidence of any condition, therapy, or laboratory
             (lab) abnormality that might confound the results of the study, interfere with the
             patient's participation for the full duration of the study or is not in the best
             interest of the patient to participate

          -  Patient has a history of a gastrointestinal surgery or other procedures that might, in
             the opinion of the investigator, interfere with the absorption or swallowing of the
             study drugs

          -  EXCLUSION CRITERIA FOR MAINTENANCE THERAPY

          -  >= grade 2 peripheral neuropathy within 14 days before beginning maintenance therapy

          -  Prolonged QTC

          -  Poorly-controlled DM

          -  Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT

          -  Untreated systemic infection

          -  Potassium (K) and magnesium (Mg) >= grade 2 toxicity

          -  Patient had myocardial infarction within 6 months prior to enrollment 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; prior to study entry, any
             electrocardiogram (ECG) abnormality at screening must be documented by the
             investigator as not medically relevant

          -  Patient has hypersensitivity to VELCADE (bortezomib), boron, or mannitol

          -  Female subject is pregnant or lactating; confirmation that the subject is not pregnant
             must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG)
             pregnancy test result obtained during screening; pregnancy testing is not required for
             postmenopausal or surgically sterilized women

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period, or a positive urine pregnancy test on day 1 before first dose of
             study drug, if applicable

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with 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

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and throughout the duration of
             this trial

          -  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