Graft Versus Host Disease Clinical Trial
Official title:
A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention
Verified date | July 2021 |
Source | H. Lee Moffitt Cancer Center and Research Institute |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 42 |
Est. completion date | July 13, 2021 |
Est. primary completion date | December 7, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
H. Lee Moffitt Cancer Center and Research Institute | Novartis |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage | Cumulative incidence of acute GVHD grades II-IV by day 100. Investigators will consider =43% incidence of grade II-IV aGVHD not acceptable. Investigators will use 23% incidence rate of GVHD as target. GVHD severity stage and grading and distribution will be measured weekly from day of transplant to day 90 +/- 14 using standard scoring system. Stage of GVHD will be given for each site of involvement (e.g. skin, liver, and gut), as well as a composite score for overall acute GVHD grade. Pathologic confirmation of aGVHD will be dictated by usual clinical practice, and not mandated by this protocol. | 100 days post transplant | |
Secondary | Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage | GVHD with onset after 100 days post-HCT with presence of at least one diagnostic manifestation of chronic c-GVHD or distinct manifestation confirmed by biopsy or other relevant tests (e.g., PFT). Classified as: 1- Classic chronic GVHD - meets criteria for chronic GVHD and has no features consistent with aGVHD or 2-Overlap syndrome - features of acute and chronic GVHD exist together. C-GVHD will be measured prospectively in all participants on days 90+/-14 , 120 +/- 14, 150 +/- 14, 180+/- 14, 270+/- 30, and 365 +/- 30 as per standardized scoring system. | 100 days post transplant | |
Secondary | Time to Stable Engraftment | Stable engraftment for white blood count (WBC) is defined as a sustained absolute neutrophil count > 500 over 3 days without cytokine support. Stable platelet engraftments is defined as count of > 20,000 over 7 days without transfusion support. Time to engraftment is defined as time from day 0 to day of sustained engraftment per above criteria for both platelets and WBC. | 100 days post transplant | |
Secondary | Number of Participants With Primary Disease Relapse | Incidence of primary disease relapse and non-relapse related death will be reported per standard definitions. These will be treated as competing risk events. | 1 year | |
Secondary | Number of Participants With Non-relapse Mortality | Incidence of primary disease relapse and non-relapse related death will be reported per standard definitions. These will be treated as competing risk events. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation. | 1 year | |
Secondary | Percentage of Participants With Overall Survival (OS) | Overall survival: Time from transplant date to death from any cause. Time-to-event data such as overall survival is measured from the date of transplantation. OS will be analyzed using the Kaplan-Meier method. | 1 year | |
Secondary | Percentage of Participants With Relapse-free Survival (RFS) | Relapse-free survival: Time from transplant date to death or primary disease relapse. Time-to-event data such as relapse-free survival is measured from the date of transplantation. RFS will be analyzed using the Kaplan-Meier method. | 1 year |
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