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

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Completed; Phase 2

Conditions: Graft Versus Host Disease; GVHD

Treatments: Drug: Sirolimus; Drug: Tacrolimus; Drug: Panobinostat

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02588339

CLBH589US100T (Other Identifier)

MCC-18374

Details and patient eligibility

About

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).

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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42 participants in 1 patient group

Panobinostat (PANO) Therapy

Experimental group

Description:

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.

Treatment:

Drug: Tacrolimus

Drug: Sirolimus

Drug: Panobinostat