Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
Condition: Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large B-Cell, Diffuse; Mycosis Fungoides; Sezary Syndrome; Leukemia, T-Cell; Waldenstrom Macroglobulinemia; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Extranodal NK-T-Cell; Lymphoproliferative Disorders; Immunoblastic Lymphadenopathy; Recurrence
Intervention: panobinostat; laboratory biomarker analysis; western blotting; DNA analysis; flow cytometry; pharmacological study; immunohistochemistry staining method
Intervention description: Given orally; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Optional correlative studies
Intervention MeSH terms: Panobinostat; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for
      cell growth. This phase II trial is studying how well panobinostat works in treating patients
      with relapsed or refractory non-Hodgkin lymphoma
    

Eligibility criteria:

        Inclusion Criteria

          -  Biopsy-proven relapsed or refractory non-Hodgkin lymphoma requiring treatment, who
             have failed, unable to tolerate, or refused other available active therapies; patients
             should not have other treatment options considered curative (NOTE: for patients with
             lymphoma without CNS involvement, a re-biopsy is necessary unless the patient has had
             a previous biopsy =< 6 months prior to treatment on this protocol if there has been no
             intervening treatment; patients with biopsy-proven CNS lymphoma at any time are not
             required to have a rebiopsy to be eligible for this study); NOTE: relapsed NHL is
             defined as NHL that relapses after at least one prior therapy and does not have
             available curative therapy; refractory NHL is defined as NHL that has progressed or
             not responded to most recent therapy and has had at least one prior therapy and have
             no available curative therapies

          -  Measurable disease by CT or MRI or the CT portion of the PET/CT: must have at least
             one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x
             10^9/L; skin lesions can be used if the area is >= 2 cm in at least one diameter and
             photographed with a ruler

          -  The following disease types are eligible: transformed lymphomas: diffuse large B cell
             lymphoma, mantle cell lymphoma, follicular lymphoma grade III; precursor B
             lymphoblastic leukemia/lymphoma; mediastinal (thymic) large B-cell lymphoma; Burkitt
             lymphoma/leukemia; precursor T-lymphoblastic leukemia/lymphoma; primary cutaneous
             anaplastic large cell lymphoma; anaplastic large cell lymphoma - primary systemic
             type; small lymphocytic lymphoma/chronic lymphocytic leukemia; follicular lymphoma,
             grades 1, 2; extranodal marginal zone B-cell lymphoma of MALT type; nodal marginal
             zone B-cell lymphoma; splenic marginal zone B-cell lymphoma; peripheral T cell
             lymphoma, unspecified; anaplastic large cell lymphoma (T and null cell type);
             lymphoplasmacytic lymphoma (Waldenstrom Macroglobulinemia); CNS lymphoma; post
             transplant lymphoproliferative disorders; mycosis fungoides/Sezary syndrome; primary
             effusion lymphoma; blastic NK-cell lymphoma; adult T-cell leukemia/lymphoma;
             extranodal NK/T-cell lymphoma, nasal type; enteropathy-type T-cell lymphoma;
             hepatosplenic T-cell lymphoma; subcutaneous panniculitis-like T-cell lymphoma;
             angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma - primary cutaneous
             type

          -  For lymphoplasmacytic lymphoma patients without measurable lymphadenopathy, measurable
             disease can be defined by both of the following criteria: bone marrow
             lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets,
             lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy and
             quantitative IgM monoclonal protein > 1,000 mg/dL

          -  ANC >= 1000/uL

          -  Hgb >= 9 g/dl

          -  PLT >= 75,000/uL

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x
             ULN the direct bilirubin must be normal

          -  AST =< 3 x ULN

          -  Albumin > 3.0 g/dl

          -  Creatinine =< 2.5 x ULN

          -  Serum potassium, magnesium and phosphorus >= LLN and =< 1.2 x ULN

          -  Total serum calcium [corrected for serum albumin] or ionized calcium >= LLN

          -  Clinically euthyroid; patients are permitted to receive thyroid hormone supplements to
             treat underlying hypothyroidism

          -  Baseline MUGA or ECHO must demonstrate LVEF >= the lower limit of the institutional
             normal

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Willingness to return to Mayo Clinic

          -  Life expectancy >= 12 weeks

          -  Willingness to provide blood and tissues samples for research studies as required by
             the protocol

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  ECOG performance status (PS) 0, 1 or 2

        Exclusion Criteria

          -  Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

          -  Patients who will need valproic acid for any medical condition during the study or
             within 5 days prior to first panobinostat treatment

          -  Candidate for known standard therapy for the patient's disease that is potentially
             curative

          -  Uncontrolled infection requiring ongoing antibiotics

          -  Any prior therapy for lymphoma within the previous 2 weeks for standard treatments and
             within 4 weeks for experimental therapies unless the patient has recovered from the
             nadir of the previous treatment to a level that meets the inclusion criteria

          -  Receiving corticosteroids > 20mg of prednisone per day (or equivalent)

          -  Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy
             regardless of interval since last treatment

          -  Patients with congenital long QT syndrome

          -  History or presence of sustained ventricular tachyarrhythmia (patients with a history
             of atrial arrhythmia are eligible but should be discussed with the study PI prior to
             enrollment)

          -  Any history of ventricular fibrillation or torsade de pointes

          -  Bradycardia defined as HR < 50 bpm; patients with pacemakers are eligible if HR >= 50
             bpm

          -  Screening ECG with a QTcFredericia (QTcF) > 450 msec

          -  Right bundle branch block + left anterior hemiblock (bifascicular block)

          -  Patients with myocardial infarction or unstable angina =< 6 months prior registration

          -  Other clinically significant heart disease (e.g. CHF NY Heart Association class III or
             IV, uncontrolled hypertension, history of labile hypertension, or history of poor
             compliance with an antihypertensive regimen)

          -  Pregnant women or women of reproductive ability who are unwilling to use effective
             contraception during the study and for 3 months after stopping treatment

          -  Nursing women

          -  Men who are unwilling to use a condom (even if they have undergone a prior vasectomy)
             while having intercourse with any woman, while taking the drug and for 3 months after
             stopping treatment

          -  Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
             considered investigational (utilized for a non-FDA-approved indication and in the
             context of a research investigation); patients should have recovered from any
             immunotherapy, chemotherapy, or radiation therapy related toxicities

          -  Known positivity for human immunodeficiency virus (HIV) or hepatitis C with
             uncontrolled disease; baseline testing for HIV and hepatitis C is not required

          -  Active other malignancy requiring treatment that would interfere with the assessments
             of response of the lymphoma to protocol treatment

          -  Inability to swallow or impairment of gastrointestinal function or gastrointestinal
             disease that may significantly alter the absorption of the drugs (e.g. ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea > CTCAE Grade 2, malabsorption
             syndrome or small bowel resection) that would preclude use of oral medications

          -  Thrombolic or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months

          -  Any severe and/or uncontrolled medical conditions or other conditions that, in the
             treating physician's opinion, could adversely impact their ability to participate in
             the study; patients on chronic oxygen therapy, those with liver disease such as
             cirrhosis, chronic hepatitis or chronic persistent hepatitis, or uncontrolled
             infections will be excluded

          -  Concomitant use of strong or moderate CYP3A4 inhibitors

          -  Using medications that have a relative risk of prolonging the QT interval or inducing
             torsade de pointes if treatment cannot be discontinued or switched to a different
             medication prior to starting study drug

          -  Active bleeding tendency. NOTE: Patients on therapeutic anticoagulation should be
             monitored carefully to maintain therapeutic level of anticoagulation to avoid
             increased risk of bleeding due to concurrent drug induced thrombocytopenia. It is
             suggested that patients who require anticoagulation therapy while on therapy use low
             molecular weight heparin (LMWH).

          -  Major surgery =< 4 weeks prior to registration or have not recovered from side effects
             of such therapy

          -  History of other prior malignancies except for properly treated basal cell or squamous
             cell carcinoma of skin, in situ cervical cancer, in situ breast cancer or early stage
             prostate cancer