This trial is active, not recruiting.

Condition graft-versus-host disease
Treatment panobinostat (lbh589)
Phase phase 1/phase 2
Sponsor H. Lee Moffitt Cancer Center and Research Institute
Collaborator Novartis
Start date April 2010
End date November 2016
Trial size 22 participants
Trial identifier NCT01111526, CLBH589BUS20T, MCC-15618


To test a new agent, LBH589, in combination with glucocorticoids as initial therapy of acute graft versus host disease (GVHD).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
panobinostat (lbh589)
Phase I, dose escalation levels for LBH589; patients treated with LBH589 PO three times a week (48 hours apart) every week for four weeks. DL -1* 5 mg PO; DL 1 10 mg PO (starting dose level); DL 2 15 mg PO; DL 3 20 mg PO; DL 4 25 mg PO ; *DL -1, represents a potential treatment dose for patients requiring a dose reduction from a higher dose level. In addition, dose level -1 may be used as a contingency dose level if the starting dose level of LBH589 is not tolerated in the initial cohort. Phase II, patients treated with LBH589 PO (MTD to be determined) three times a week (48 hours apart) every week for four weeks

Primary Outcomes

Safety of LBH589 (Phase I)
time frame: 36 +/- 3 days from initiation of LBH589
Efficacy of LBH589 (Phase II)
time frame: 36 +/- 3 days from initiation of LBH589

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Patients receiving allogeneic hematopoietic cell transplantation (HCT) with peripheral blood, bone marrow or cord blood stem cells regardless of initial diagnosis who develop a clinical diagnosis of acute GVHD as defined in Section 2 diagnosed and treated with systemic glucocorticoids within 72 hours prior to enrollment. Biopsy of involved skin and gastrointestinal tract is strongly encouraged, but not required for study entry. For patients with aspartic transaminase (AST) or alanine transaminase (ALT) or Alkaline phosphatase with gamma-glutamyltransferase (GGT) elevations without bilirubin elevation must have a liver biopsy to document GVHD diagnosis. Patients should meet one of the following criteria: If GVHD is present in an isolated organ: 1. Skin rash involvement of a minimum of 50% of body surface area in absence of documented drug allergy or infectious etiology. 2. Diarrhea with a minimum stool volume of 500 mL/day and/or a minimum of 2 stools above baseline/day in absence of enterocolitis from C. difficile or other documented pathogens. 3. Increase in bilirubin above upper limit of normal (ULN) in absence of clinically defined veno-occlusive disease. 4. Isolated increased AST and/or ALT and/or increased alkaline phosphatase above ULN with GGT elevation above ULN with documented liver GVHD biopsy. If GVHD presentation involves >/= 2 organs: GVHD Grade >/= II as defined in Table D of protocol. 2. Male or female patients aged 18 or older at time of enrollment 3. Signed informed consent 4. Absolute neutrophil count (ANC) greater than 500/μL, platelets >/= 20 x 10^9/L supported by platelet transfusion and hemoglobin >/= 8 g/dl supported by red cell transfusion. 5. Calculated creatinine clearance (CrCl) >/= 30 mL/min (MDRD Formula) 6. Serum potassium >/= lower limit of normal (LLN), Total serum calcium [corrected for serum albumin] or ionized calcium >/= LLN, Serum magnesium >/= LLN and Serum phosphorus >/= LLN on the day of LBH589 administration 7. Thyroid-stimulating hormone (TSH) /= the lower limit of the institutional normal before transplantation. Exclusion Criteria: 1. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 24 hrs of receiving the first dose of study medication if a pregnancy test was not done pre-transplant. Male patients whose sexual partners are WOCBP not using effective birth control 2. Patients requiring mechanical ventilation support. 3. Active, uncontrolled life threatening viral or fungal disease, such as cytomegalovirus (CMV) pneumonia or gastroenteritis, Aspergillus pneumonia or brain abscess. For bacterial or viral infections, patients must be receiving therapy and have no signs of progression for 48 hours prior to enrollment. For fungal infection patients must be receiving systemic anti-fungal therapy and have no signs of progression for 1 week prior to enrollment. Progressing infection is defined as hemo-dynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infections. Persisting fever without other signs of symptoms will not be interpreted as progressing infections. 4. Receipt of other investigational new drugs for GVHD including agents used for GVHD prophylaxis within 30 days. The following agents are not considered experimental and therefore are not excluded: cyclosporine, tacrolimus, sirolimus, glucocorticoids, antithymocyte globulin, replacement corticosteroid therapy for hypoadrenalism and methotrexate. 5. HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days. 6. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment. 7. Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: 1. Patients with congenital long QT syndrome. 2. History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of a controlled atrial arrhythmia are eligible). 3. Any history of ventricular fibrillation or torsade de pointes. 4. Bradycardia defined as heart rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR >/= 50 bpm. 5. Patients are excluded if the average of the QT Corrected by the Fridericia Formula (QTcF) is > 470 msec on the screening EKGs. 6. Right bundle branch block + left anterior hemiblock (bifascicular block). 7. Patients with myocardial infarction or unstable angina

Additional Information

Official title A Phase I/II Trial Evaluating the Use of Histone Deacetylase Inhibitor LBH589 in Addition to Corticosteroids in Patients With Acute Graft Versus Host Disease
Principal investigator Lia Perez, MD
Description Dose escalation study to test the safety (Phase I), pharmacology and preliminary clinical activity (Phase II) of a Novel histone deacetylase (HDAC) inhibitor, LBH589, in the treatment of the following GVHD presentations: Classic, Late-onset acute GVHD, Recurrent acute GVHD, Overlap syndrome.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by H. Lee Moffitt Cancer Center and Research Institute.