Clinical Trial 18374

Cancer Type: Malignant Hematology
Interventions:Not Applicable; Panobinostat (LBH589)

Study Type: Prevention
Phase of Study: Phase II
Investigators:

  • Lia Perez

Overview

Study Title

A Phase II Trial Evaluating the use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention

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).

Objective

To prospectively determine the cumulative incidence of acute GVHD grades II-IV by day 100 when combining PANO with standard combination of TAC/SIR for GVHD prevention. It is anticipated that the combination will decrease of acute GVHD risk to 30% compared to our historical control of 50% with TAC/SIR alone. Secondary: Cumulative incidence of chronic GVHD; Engraftment, relapse, non-relapse mortality, overall and relapse-free survival at one year. Biological studies to test the pharmacodynamics of TAC/SIR/PANO combination for GVHD prevention.

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) > 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 less than 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 less than 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) 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.