Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention
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|ClinicalTrials.gov Identifier: NCT02588339|
Recruitment Status : Active, not recruiting
First Posted : October 27, 2015
Last Update Posted : September 9, 2019
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease GVHD||Drug: Panobinostat Drug: Sirolimus Drug: Tacrolimus||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention|
|Actual Study Start Date :||February 23, 2016|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2020|
Experimental: Panobinostat (PANO) Therapy
Participants will be treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants will receive PANO, Sirolimus and Tacrolimus.
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 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 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.
- Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) [ Time Frame: 100 days post transplant ]Participants who receive at least one dose of the study drug (PANO) per protocol will be eligible for primary and secondary endpoints. 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.
- Cumulative Incidence of Chronic Graft Versus Host Disease (GVHD) [ Time Frame: 100 days post transplant ]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.
- Stable Engraftment [ Time Frame: 100 days post transplant ]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.
- Primary Disease Relapse [ Time Frame: 1 year ]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 Mortality [ Time Frame: 1 year ]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.
- Overall Survival (OS) [ Time Frame: 1 year ]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.
- Relapse-free Survival (RFS) [ Time Frame: 1 year ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02588339
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Lia Perez, M.D.||H. Lee Moffitt Cancer Center and Research Institute|