Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention
Condition: Graft Versus Host Disease; GVHD
MeSH terms: Graft vs Host Disease
Intervention: Panobinostat; Sirolimus; Tacrolimus
Intervention description: Panobinostat (PANO) will begin 5 days (Day -5) before transplant day (Day 0). All participants will take PANO by mouth once a day, three times a week (48 hours apart), every week for 26 weeks (approximately 6 months). PANO will be provided by Novartis as 5-mg pink gelatin capsules.; Sirolimus will be given the day before transplant and continued daily for at least one year. SIR will be administered starting on day -1 and thereafter. Dosing will be adjusted to maintain therapeutic targets per Moffitt institutional standards.; Tacrolimus as an infusion or as a pill will begin 3 days before transplant (day -3) and following Moffitt institutional guidelines for dosing. Tacrolimus will be given for at least 50 days and participants will remain on Tacrolimus for as long as it is necessary per standard of care.
Intervention MeSH terms: Sirolimus; Panobinostat; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hematologic disorder; allogeneic hematopoietic cell transplantation

Summary:

      This study will test PANO in combination with tacrolimus/sirolimus (TAC/SIR) for acute GVHD
      prevention. The purpose of this study is to determine if Panobinostat (PANO) when used in
      combination with sirolimus and tacrolimus will help reduce the incidence of Graft-vs-host
      disease (GVHD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years or older at time of enrollment

          -  Signed informed consent

          -  Hematologic disorder requiring allogeneic hematopoietic cell transplantation

          -  Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition
             (MUGA) scan or echocardiogram

          -  Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and
             diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on
             pulmonary function tests

          -  Transaminases (AST, ALT) < 3 times upper limit of normal (ULN) values

          -  Creatinine clearance calculated ≥ 50 mL/min

          -  Karnofsky Performance Status Score ≥ 60%.

          -  Human leukocyte antigen (HLA) matched 8/8 (A, B, C, DRB1) related or unrelated donor

        Exclusion Criteria:

          -  Active infection not controlled with appropriate antimicrobial therapy

          -  HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are
             eligible), or hepatitis C infection

          -  Sorror's co-morbidity factors with total score > 4. Important modification to
             co-morbidity index calculation: DLCO adjusted will not be included in assessment of
             pulmonary risk, except those patients with DLCO adjusted < 50% who are excluded from
             the trial.

          -  Anti-thymocyte globulin (ATG) as part of the conditioning regimen

          -  Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis

          -  Pregnancy

          -  Histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment
             of cancer within 30 days

          -  Patients who will need valproic acid for any medical condition during the study or
             within 5 days prior to first PANO treatment

          -  Impaired cardiac function or clinically significant cardiac diseases, including any
             one of the following: Any history of ventricular fibrillation or torsade de pointes;
             Bradycardia defined as heart rate (HR)< 45 bpm (Patients with pacemakers are eligible
             if HR ≥ 45 bpm); Screening electrocardiogram (ECG) with a QTcF > 480 msec; Right
             bundle branch block + left anterior hemiblock (bifascicular block); Patients with
             myocardial infarction or unstable angina ≤ 12 months prior to starting study drug;
             Other clinically significant heart disease (e.g., New York Heart Association (NYHA)
             class III or IV , uncontrolled hypertension) as per discretion of principal
             investigator and/or treating physician; Patients 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 with the exception of drugs listed on Appendix B of study
             documents that are required for hematopoietic cell transplantation (HCT) patients.