Intervention: Panobinostat
Trial phase: Phase 2
ATC code: L01XH03 | L01XX42
SMILES: Cc1[nH]c2ccccc2c1CCNCc1ccc(/C=C/C(=O)NO)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 41
Group description: Patients receive oral 40 mg panobinostat 3 times weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
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