Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention

NCT02588339 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MCC-18374CLBH589US100T
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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).

Conditions

Graft Versus Host Disease; GVHD

Keywords

Hematologic disorder; allogeneic hematopoietic cell transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage

  100 days post transplant

• Time to Stable Engraftment

  100 days post transplant

• Number of Participants With Primary Disease Relapse

  1 year

• Number of Participants With Non-relapse Mortality

  1 year

• Percentage of Participants With Overall Survival (OS)

  1 year

Study Arms (1)

Panobinostat (PANO) Therapy

EXPERIMENTAL

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.

Drug: Panobinostat; Drug: Sirolimus; Drug: Tacrolimus

Interventions

Panobinostat DRUG

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.

Also known as: PANO, Farydak, LBH-589

Panobinostat (PANO) Therapy

Sirolimus DRUG

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.

Also known as: SIR, Rapamune

Panobinostat (PANO) Therapy

Tacrolimus DRUG

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.

Also known as: TAC, Prograf

Panobinostat (PANO) Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (2)

• Lakshmanan AP, Deola S, Terranegra A. The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease. Transplantation. 2023 Dec 1;107(12):2497-2509. doi: 10.1097/TP.0000000000004629. Epub 2023 May 16.

  PMID: 37189240 DERIVED

• 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.

  PMID: 34242388 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Diseases

Interventions

Panobinostat; Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Immune System Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones

Results Point of Contact

• Title: Lia E. Perez, MD
• Organization: Moffitt Cancer Center

Lia.Perez@moffitt.org

813-745-3665

Study Officials

• Lia Perez, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: October 27, 2015
• Study Start: March 4, 2016
• Primary Completion: December 7, 2018
• Study Completion: July 13, 2021
• Last Updated: July 21, 2021
• Results First Posted: January 3, 2020

Record last verified: 2021-07

Locations

US (1)