Trial Outcomes & Findings for Histone Deacetylase Inhibitor LBH589 in Addition to Corticosteroids in Patients With Acute Graft Versus Host Disease (GVHD) (NCT NCT01111526)

Last Updated: 2018-05-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

22 participants

Primary outcome timeframe

2 years, 8 months

Results posted on

2018-05-15

Participant Flow

Participants were enrolled at Moffitt Cancer Center, September 2010 through December 2014.

Participant milestones

Participant milestones
Measure	Phase I Participants Not Evaluable for MTD Participants who began treatment before the formulation change.	Phase I Participants Evaluable for MTD Participants treated after the formulation change.	Phase II Participants Treated at MTD All participants enrolled during Phase II.
Overall Study STARTED	4	8	10
Overall Study COMPLETED	4	7	8
Overall Study NOT COMPLETED	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Participants Not Evaluable for MTD Participants who began treatment before the formulation change.	Phase I Participants Evaluable for MTD Participants treated after the formulation change.	Phase II Participants Treated at MTD All participants enrolled during Phase II.
Overall Study GVHD Disease Progression	0	1	2

Baseline Characteristics

Histone Deacetylase Inhibitor LBH589 in Addition to Corticosteroids in Patients With Acute Graft Versus Host Disease (GVHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LBH589, in Addition to Glucocorticoids n=22 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=99 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants
Age, Continuous	55 years n=99 Participants
Sex: Female, Male Female	8 Participants n=99 Participants
Sex: Female, Male Male	14 Participants n=99 Participants
Region of Enrollment United States	22 participants n=99 Participants

PRIMARY outcome

Timeframe: 2 years, 8 months

Population: All participants treated with Oral Formulation LBH589, during Phase I Dose Escalation.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=8 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Phase I: Maximum Tolerated Dose (MTD) in Milligrams	5 MTD of oral LBH589 in milligrams

PRIMARY outcome

Timeframe: 1 year, 2 months

Population: All participants treated at maximum tolerated dose (MTD) of Oral Formulation LBH589, and evaluable at planned time of analysis.

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.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=16 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Phase II: Overall Rate of Response (ORR) Complete Response	13 participants
Phase II: Overall Rate of Response (ORR) Partial Response	2 participants
Phase II: Overall Rate of Response (ORR) Progressive Disease	1 participants
Phase II: Overall Rate of Response (ORR) Stable Disease	0 participants

SECONDARY outcome

Timeframe: Up to 36 days per participant

Population: All participants that received Oral Formulation LBH589 at MTD (5 mg) 3 times per week, for 4 weeks.

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.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=16 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Incidence of GVHD Flares Requiring Increasing Immune Suppressive Therapy	1 participants

SECONDARY outcome

Timeframe: 1 year

Population: All participants that received Oral Formulation LBH589 at MTD (5 mg) 3 times per week, for 4 weeks.

Overall Survival (OS) at one year post initiation of therapy.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=16 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Overall Survival (OS) OS at 1 year	11 participants
Overall Survival (OS) Death before 1 year: sepsis	1 participants
Overall Survival (OS) Death before 1 year: relapse	2 participants
Overall Survival (OS) Death before 1 year: GVHD	1 participants
Overall Survival (OS) Death before 1 year: Cardiogenic shock	1 participants

SECONDARY outcome

Timeframe: 1 year

Population: All participants that received Oral Formulation LBH589 at MTD (5 mg) 3 times per week, for 4 weeks and were evaluable at 365 days.

Number of participants discontinuing all immune suppression without subsequent flare by 1 year post initiation of therapy.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=11 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Occurrence of Discontinuation of All Immune Suppression	0 participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: All participants that received Oral Formulation LBH589 at MTD (5 mg) 3 times per week, for 4 weeks.

Chronic GVHD onset in participants without overlap syndrome at initiation of study therapy. Number of participants with overlap syndrome at MTD.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=16 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Chronic GVHD Onset	6 participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: All participants that received Oral Formulation LBH589 at MTD (5 mg) 3 times per week, for 4 weeks, had overlap syndrome at MTD and were evaluable at time of analysis.

Chronic GVHD maximum severity grade at MTD, in participants without overlap syndrome at initiation of study therapy. Maximum c-GVHD severity: Mild, Moderate, Severe.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=5 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Chronic GVHD Severity at MTD Mild	2 participants
Chronic GVHD Severity at MTD Moderate	1 participants
Chronic GVHD Severity at MTD Severe	1 participants

SECONDARY outcome

Timeframe: 1 year

Population: All participants that received Oral Formulation LBH589 at MTD (5 mg) 3 times per week, for 4 weeks, had overlap syndrome at MTD and were evaluable at 1 year.

Stable or improved Chronic GVHD score: Improved Mild to None; Improved Severe to Moderate; Improved Moderate to None, Remained Stable at Mild.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=5 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Stable or Improved Chronic GVHD Severity Score Improved: Mild to None	1 participants
Stable or Improved Chronic GVHD Severity Score Improved: Severe to Moderate	1 participants
Stable or Improved Chronic GVHD Severity Score Improved: Moderate to None	1 participants
Stable or Improved Chronic GVHD Severity Score Stable: Remained Stable at Mild	1 participants

SECONDARY outcome

Timeframe: 5 years, 3 months

Population: All participants

Number of participants with adverse events possibly related to study treatment, per event category.

Outcome measures

Outcome measures
Measure	LBH589, in Addition to Glucocorticoids n=22 Participants Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Occurrence of Possibly Related Adverse Events Thrombocytopenia	11 participants
Occurrence of Possibly Related Adverse Events Leukopenia	6 participants
Occurrence of Possibly Related Adverse Events Anemia	2 participants
Occurrence of Possibly Related Adverse Events Hypertriglyceridemia	5 participants
Occurrence of Possibly Related Adverse Events Hypercholesterolemia	3 participants
Occurrence of Possibly Related Adverse Events Fatigue	1 participants
Occurrence of Possibly Related Adverse Events Hepatobiliary disorders	1 participants

Adverse Events

LBH589, in Addition to Glucocorticoids

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LBH589, in Addition to Glucocorticoids n=22 participants at risk Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Blood and lymphatic system disorders Anemia	13.6% 3/22 • Number of events 3 • 5 years, 3 months All participants. All events are listed regardless of causality.
Blood and lymphatic system disorders Thrombocytopenia	13.6% 3/22 • Number of events 4 • 5 years, 3 months All participants. All events are listed regardless of causality.
Blood and lymphatic system disorders Pancytopenia	9.1% 2/22 • Number of events 2 • 5 years, 3 months All participants. All events are listed regardless of causality.
Blood and lymphatic system disorders Hyponatremia	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Atrial fibrillation	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Atrial flutter	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Cardiac disorders - Other, Hypotension	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Heart failure	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Gastrointestinal disorders Gastrointestinal disorders - Other, severe diarrhea	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Gastrointestinal disorders Gastrointestinal disorders - Other, GVHD/VOD	4.5% 1/22 • Number of events 2 • 5 years, 3 months All participants. All events are listed regardless of causality.
Gastrointestinal disorders Gastrointestinal disorders - Other, Severe GVHD	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Gastrointestinal disorders Gastrointestinal pain	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Hepatobiliary disorders Hepatic failure	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Hepatobiliary disorders Hepatobiliary disorders - Other, suspected drug toxicity to liver	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Infections and infestations Infections and infestations - Other, cellulitis	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Infections and infestations Sepsis	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Metabolism and nutrition disorders Hypertriglyceridemia	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Renal and urinary disorders Renal and urinary disorders - Other, put on dialysis	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Skin and subcutaneous tissue disorders Toxic epidermal necrolysis	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.

Other adverse events

Other adverse events
Measure	LBH589, in Addition to Glucocorticoids n=22 participants at risk Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Investigations Platelet count decreased	86.4% 19/22 • Number of events 43 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations White blood cell decreased	54.5% 12/22 • Number of events 21 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Cholesterol high	50.0% 11/22 • Number of events 17 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Alkaline phosphatase increased	22.7% 5/22 • Number of events 5 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Neutrophil count decreased	22.7% 5/22 • Number of events 6 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Blood bilirubin increased	13.6% 3/22 • Number of events 3 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Alkaline aminotransferase increased	22.7% 5/22 • Number of events 6 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Aspartate aminotransferase increased	9.1% 2/22 • Number of events 2 • 5 years, 3 months All participants. All events are listed regardless of causality.
Investigations Creatinine increased	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Vascular disorders Hypertension	72.7% 16/22 • Number of events 35 • 5 years, 3 months All participants. All events are listed regardless of causality.
Vascular disorders Hypotension	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Metabolism and nutrition disorders Hypertriglyceridemia	63.6% 14/22 • Number of events 36 • 5 years, 3 months All participants. All events are listed regardless of causality.
Metabolism and nutrition disorders Hyperglycemia	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Blood and lymphatic system disorders Anemia	31.8% 7/22 • Number of events 10 • 5 years, 3 months All participants. All events are listed regardless of causality.
Gastrointestinal disorders Diarrhea	9.1% 2/22 • Number of events 3 • 5 years, 3 months All participants. All events are listed regardless of causality.
Gastrointestinal disorders Nausea	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
General disorders Edema limbs	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
General disorders Fatigue	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Cardiac disorders - Other, cardiac arrhythmia	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Sinus tachycardia	9.1% 2/22 • Number of events 4 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Ventricular arrhythmia	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Renal and urinary disorders Acute kidney injury	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.1% 2/22 • Number of events 2 • 5 years, 3 months All participants. All events are listed regardless of causality.
Psychiatric disorders Anxiety	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Psychiatric disorders Insomnia	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.
Cardiac disorders Cardiovascular toxicity	4.5% 1/22 • Number of events 1 • 5 years, 3 months All participants. All events are listed regardless of causality.

Additional Information

Dr. Lia Perez

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-3665

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place