Clinical trial NCT02588339: Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention
Official title: A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
GVHD
Keywords: Hematologic disorder
allogeneic hematopoietic cell transplantation
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2015-10-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Primary outcomes:
measure: Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
timeFrame: 100 days post transplant
Secondary outcomes:
measure: Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage
timeFrame: 100 days post transplant
measure: Time to Stable Engraftment
timeFrame: 100 days post transplant
measure: Number of Participants With Primary Disease Relapse
timeFrame: 1 year
measure: Number of Participants With Non-relapse Mortality
timeFrame: 1 year
measure: Percentage of Participants With Overall Survival (OS)
timeFrame: 1 year
measure: Percentage of Participants With Relapse-free Survival (RFS)
timeFrame: 1 year
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Lia Perez, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perez L, Fernandez H, Kharfan-Dabaja M, Khimani F, Betts B, Mishra A, Ayala E, Locke FL, Ochoa-Bayona L, Nieder M, Pidala J, Achille A, Powers J, Sahakian E, Thapa R, Wang X, Anasetti C. A phase 2 trial of the histone deacetylase inhibitor panobinostat for graft-versus-host disease prevention. Blood Adv. 2021 Jul 13;5(13):2740-2750. doi: 10.1182/bloodadvances.2021004225.