Histone Deacetylase Inhibitor LBH589 in Addition to Corticosteroids in Patients With Acute Graft Versus Host Disease (GVHD)
|ClinicalTrials.gov Identifier: NCT01111526|
Recruitment Status : Completed
First Posted : April 27, 2010
Results First Posted : December 22, 2016
Last Update Posted : May 15, 2018
|Condition or disease||Intervention/treatment||Phase|
|Graft-Versus-Host Disease||Drug: Panobinostat (LBH589)||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||April 2010|
|Actual Primary Completion Date :||October 2015|
|Actual Study Completion Date :||June 2016|
Experimental: LBH589, in Addition to Glucocorticoids
Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Drug: Panobinostat (LBH589)
Phase I Initial Treatment Plan - Intravenous (IV) Formulation: Up to 4 dose levels (DL) of LBH589 IV formulation to establish LBH589 Maximum Tolerated Dose (MTD) in acute GVHD treatment. The first 4 participants began this treatment plan, before the IV Formulation became unavailable.
DL -1: 1.25 mg/m^2 IV; DL 1: 2.5 mg/m^2 IV; DL 2: 5 mg/m^2 IV; DL 3: 7.5 mg/m^2 IV; DL 4: 10 mg/m^2 IV.
Phase I Revised Treatment Plan - Oral Formulation (to replace IV Formulation): Dose escalation levels for LBH589; participants treated with LBH589 by mouth (PO) 3 times a week (48 hours apart) every week for 4 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.
Phase II Treatment Plan: LBH589 PO at MTD, 3 times a week (48 hours apart) every week for 4 weeks.
- Phase I: Maximum Tolerated Dose (MTD) in Milligrams [ Time Frame: 2 years, 8 months ]MTD of LBH589 in addition to glucocorticoids as treatment for Graft Versus Host Disease (GVHD) manifestations. MTD in Milligrams (mg), taken by mouth (PO), 3 times per week, for 4 weeks. The oral formulation replaced the IV formulation (which became unavailable) after the first 4 participants were treated. Dose limiting toxicity (DLT) is defined by the occurrence of Common Toxicity Criteria (CTC) grade 3 or greater toxicity that is unexpected with transplantation, except for hematological toxicity, where DLT is defined as absolute neutrophil count (ANC) <750, and for those participants who were platelet transfusion independent is defined as platelets <10 K.
- Phase II: Overall Rate of Response (ORR) [ Time Frame: 1 year, 2 months ]Rate of Complete Response (CR), Partial Response (PR), Progressive Disease (PD) and Stable Disease (SD). Assessment of GVHD will include the skin, liver and gut. Other possible etiologies of organ disease such as C difficile enterocolitis, viral infection, drug reaction, veno-occlusive disease of the liver, etc., will be excluded by appropriate tests. CR is defined as resolution of GVHD in all evaluable organs with no subsequent additional treatment given for acute GVHD. PR is defined as improvement in ≥ one evaluable organ without deterioration in at least one other. PD is defined as deterioration in at least on evaluable organ. SD is defined as the absence of any difference sufficient to meet minimal criteria for improvement or deterioration in any evaluable organs.
- Incidence of GVHD Flares Requiring Increasing Immune Suppressive Therapy [ Time Frame: Up to 36 days per participant ]Number of participants with GVHD flares requiring increasing immune suppressive therapy within 36 days of study initiation. Cumulative incidence of GVHD flares requiring increasing immune suppressive therapy will be analyzed using the competing risk method by Gray (1988). GVHD flares (progressive disease (PD)) may result in discontinuation from Panobinostat.
- Overall Survival (OS) [ Time Frame: 1 year ]Overall Survival (OS) at one year post initiation of therapy.
- Occurrence of Discontinuation of All Immune Suppression [ Time Frame: 1 year ]Number of participants discontinuing all immune suppression without subsequent flare by 1 year post initiation of therapy.
- Chronic GVHD Onset [ Time Frame: Up to 1 year ]Chronic GVHD onset in participants without overlap syndrome at initiation of study therapy. Number of participants with overlap syndrome at MTD.
- Chronic GVHD Severity at MTD [ Time Frame: Up to 1 year ]Chronic GVHD maximum severity grade at MTD, in participants without overlap syndrome at initiation of study therapy. Maximum c-GVHD severity: Mild, Moderate, Severe.
- Stable or Improved Chronic GVHD Severity Score [ Time Frame: 1 year ]Stable or improved Chronic GVHD score: Improved Mild to None; Improved Severe to Moderate; Improved Moderate to None, Remained Stable at Mild.
- Occurrence of Possibly Related Adverse Events [ Time Frame: 5 years, 3 months ]Number of participants with adverse events possibly related to study treatment, per event category.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01111526
|United States, Florida|
|H Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Lia Perez, MD||H. Lee Moffitt Cancer Center and Research Institute|