This phase II trial studies how well panobinostat works in preventing graft-versus-host disease (GVHD) in patients with hematologic disorders (begins in blood-forming tissue, such as the bone marrow, or in cells of the immune system) undergoing donor stem cell transplant. GVHD is a disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Panobinostat may help suppress the immune system (cells in the body that can cause GVHD), reduce the release of proteins (cytokines) that may contribute to inflammation in GVHD and increase production of cells (T regulatory cells) that can help to protect against GVHD.
Additional locations may be listed on ClinicalTrials.gov for NCT02588339.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To prospectively determine the cumulative incidence of acute GVHD grades II-IV by day 100 when combining PANO (panobinostat) with standard combination of TAC (tacrolimus)/SIR (sirolimus) for GVHD prevention.
SECONDARY OBJECTIVES:
I. Cumulative incidence of chronic GVHD. (Clinical Objectives)
II. Engraftment, relapse, non-relapse mortality, overall and relapse-free survival at one year. (Clinical Objectives)
III. Immune reconstitution determined by flow cytometry; histone acetylation of T cells and dendritic cell (DC) subsets by western blot and flow cytometry; regulatory T cell (T reg) immune-reconstitution, Foxp3+ expression and acetylation by flow cytometry; inflammatory cytokine and biomarker expression profiling; signal transducer and activator of transcription 3 (stat-3) activation and acetylation; panobinostat pharmacokinetics. (Biological studies to test the pharmacodynamics of TAC/SIR/PANO combination for GVHD prevention)
OUTLINE:
CONDITIONING REGIMEN: Patients receive either myeloablative busulfan and fludarabine phosphate; reduced-intensity (RIC) busulfan and fludarabine phosphate; or RIC fludarabine phosphate and melphalan per physician discretion.
GVHD PROPHYLAXIS: Patients receive panobinostat orally (PO) 3 times a week (TIW) on days -5 and continuing for 26 weeks. Patients then receive tacrolimus PO or intravenously (IV) on days -3 to 50 with suggested taper and sirolimus PO daily on days -1 to 365 with suggested taper per institutional standards.
After completion of study treatment, patients are followed up weekly for 100 days for acute GVHD and on days +90 +/- 14, 120 +/- 14, 150 +/- 14, 180+/- 14, 270+/- 30, and 360 +/- 30 for chronic-GVHD assessment and adverse events toxicity assessment.
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorLia Elena Perez