Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02588339
Other study ID # MCC-18374
Secondary ID CLBH589US100T
Status Completed
Phase Phase 2
First received
Last updated
Start date March 4, 2016
Est. completion date July 13, 2021

Study information

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

Clinical Trial 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).


Recruitment information / eligibility

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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Panobinostat
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
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
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.

Locations

Country Name City State
United States H. Lee Moffitt Cancer Center and Research Institute Tampa Florida

Sponsors (2)

Lead Sponsor Collaborator
H. Lee Moffitt Cancer Center and Research Institute Novartis

Country where clinical trial is conducted

United States, 

Outcome

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
See also
  Status Clinical Trial Phase
Recruiting NCT03357159 - Anti T-lymphocyte Immunoglobulin With Post Transplant Cyclophosphamide to Prevent GVHD Post Allogeneic Transplantation Phase 2
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Terminated NCT02877082 - Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients Phase 2
Recruiting NCT01385124 - Cannabidiol for Graft Versus Host Disease (GVHD) Prophylaxis in Allogeneic Stem Cell Transplantation Phase 1/Phase 2
Withdrawn NCT01616680 - Brentuximab Vedotin in Treating Patients With Steroid-Resistant Acute Graft-Versus-Host Disease Phase 2
Recruiting NCT01810926 - T&B Depletion Non Malignant Phase 2
Completed NCT01379209 - Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT) Phase 1/Phase 2
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Recruiting NCT00986557 - T-Lymphocyte Infusion or Standard Therapy in Treating Patients at Risk of Cytomegalovirus Infection After a Donor Stem Cell Transplant Phase 2
Enrolling by invitation NCT00972660 - Safety and Efficacy Study of Allogenic Mesenchymal Stem Cells to Treat Extensive Chronic Graft Versus Host Disease Phase 2
Terminated NCT00555048 - Alemtuzumab, Busulfan, and Cyclophosphamide Followed By a Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer Phase 1/Phase 2
Terminated NCT00373815 - Everolimus in Combination With Cyclosporine A and Prednisolone for the Treatment of Graft Versus Host Disease Phase 1
Terminated NCT00608517 - Treatment of Single or Double Umbilical Cord Trans + Graft-versus-host Disease (GVHD) Prophylaxis w/ Tacrolimus & Mycophenolate Mofetil N/A
Completed NCT00056875 - Recombinant Human Keratinocyte Growth Factor in Unrelated and Related Transplants Phase 1/Phase 2
Recruiting NCT05808985 - Intestinal Microbiome-based Research for the Prevention of Acute GVHD Phase 2
Completed NCT00813618 - Study of MEDI 507 in the Treatment of Pediatric Patients Phase 1
Completed NCT00003398 - Bone Marrow Transplantation in Treating Patients With Hematologic Cancer Phase 4
Terminated NCT00005641 - Removal of T Cells to Prevent Graft-Versus-Host Disease in Patients Undergoing Bone Marrow Transplantation Phase 2
Completed NCT02663622 - Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002) Phase 2
Completed NCT00577278 - A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan Phase 2