Trial Outcomes & Findings for Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention (NCT NCT02588339)
NCT ID: NCT02588339
Last Updated: 2021-07-21
Results Overview
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.
COMPLETED
PHASE2
42 participants
100 days post transplant
2021-07-21
Participant Flow
Participants recruited between March 2016 and August 2018
Participant milestones
| Measure |
Panobinostat (PANO) Therapy
Participants treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants received PANO, Sirolimus and Tacrolimus. GVHD graded using NIH criteria, scores of 0-3 per area of involvement (e.g; skin, liver and gut) 0 being no symptoms and 3 being symptomatic, over 50% of waking hours in bed, ECOG 3-4.
|
|---|---|
|
Overall Study
STARTED
|
42
|
|
Overall Study
COMPLETED
|
39
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Panobinostat (PANO) Therapy
Participants treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants received PANO, Sirolimus and Tacrolimus. GVHD graded using NIH criteria, scores of 0-3 per area of involvement (e.g; skin, liver and gut) 0 being no symptoms and 3 being symptomatic, over 50% of waking hours in bed, ECOG 3-4.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
GVHD Progression prior to treatment
|
2
|
Baseline Characteristics
Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention
Baseline characteristics by cohort
| Measure |
Panobinostat (PANO) Therapy
n=42 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=99 Participants
|
|
Age, Continuous
|
58 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
42 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 100 days post transplantCumulative 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.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=7 Participants
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.
|
|---|---|
|
Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
Grade II GVHD
|
6 Participants
|
|
Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
Grade III GVHD
|
1 Participants
|
SECONDARY outcome
Timeframe: 100 days post transplantGVHD with onset after 100 days post-HCT with presence of at least one diagnostic manifestation of chronic c-GVHD or distinct manifestation confirmed by biopsy or other relevant tests (e.g., PFT). Classified as: 1- Classic chronic GVHD - meets criteria for chronic GVHD and has no features consistent with aGVHD or 2-Overlap syndrome - features of acute and chronic GVHD exist together. C-GVHD will be measured prospectively in all participants on days 90+/-14 , 120 +/- 14, 150 +/- 14, 180+/- 14, 270+/- 30, and 365 +/- 30 as per standardized scoring system.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=12 Participants
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.
|
|---|---|
|
Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage
Mild GVHD
|
10 Participants
|
|
Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage
Moderate GVHD
|
2 Participants
|
SECONDARY outcome
Timeframe: 100 days post transplantPopulation: Participants with stable engraftment were analyzed
Stable engraftment for white blood count (WBC) is defined as a sustained absolute neutrophil count \> 500 over 3 days without cytokine support. Stable platelet engraftments is defined as count of \> 20,000 over 7 days without transfusion support. Time to engraftment is defined as time from day 0 to day of sustained engraftment per above criteria for both platelets and WBC.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=38 Participants
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.
|
|---|---|
|
Time to Stable Engraftment
ANC engraftment
|
15 days
Interval 12.0 to 21.0
|
|
Time to Stable Engraftment
Platelet engraftment
|
16 days
Interval 9.0 to 31.0
|
SECONDARY outcome
Timeframe: 1 yearIncidence of primary disease relapse and non-relapse related death will be reported per standard definitions. These will be treated as competing risk events.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=39 Participants
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.
|
|---|---|
|
Number of Participants With Primary Disease Relapse
|
7 Participants
|
SECONDARY outcome
Timeframe: 1 yearIncidence of primary disease relapse and non-relapse related death will be reported per standard definitions. These will be treated as competing risk events. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=39 Participants
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.
|
|---|---|
|
Number of Participants With Non-relapse Mortality
|
1 Participants
|
SECONDARY outcome
Timeframe: 1 yearOverall survival: Time from transplant date to death from any cause. Time-to-event data such as overall survival is measured from the date of transplantation. OS will be analyzed using the Kaplan-Meier method.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=39 Participants
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.
|
|---|---|
|
Percentage of Participants With Overall Survival (OS)
|
87 percentage of participants
|
SECONDARY outcome
Timeframe: 1 yearRelapse-free survival: Time from transplant date to death or primary disease relapse. Time-to-event data such as relapse-free survival is measured from the date of transplantation. RFS will be analyzed using the Kaplan-Meier method.
Outcome measures
| Measure |
Panobinostat (PANO) Therapy
n=39 Participants
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.
|
|---|---|
|
Percentage of Participants With Relapse-free Survival (RFS)
|
77 percentage of participants
|
Adverse Events
Panobinostat (PANO) Therapy
Serious adverse events
| Measure |
Panobinostat (PANO) Therapy
n=39 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Chest pain - cardiac
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Vascular disorders
Hypertension
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Infections and infestations
Upper respiratory infection
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Cardiac disorders
Atrial fibrillation
|
2.6%
1/39 • Number of events 2 • 3 years, 6 months
|
|
Metabolism and nutrition disorders
Anorexia
|
2.6%
1/39 • Number of events 2 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Sinus disorder
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders -Other
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Psychiatric disorders
Confusion
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Infections and infestations
Sepsis
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Gastrointestinal disorders
Enterocolitis
|
7.7%
3/39 • Number of events 3 • 3 years, 6 months
|
|
Gastrointestinal disorders
Nausea
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Immune system disorders
Immune system disorders -Other
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Infections and infestations
Sinusitis
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Immune system disorders
Allergic reaction
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
12.8%
5/39 • Number of events 5 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Nervous system disorders
Akathisia
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
General disorders
Edema limbs
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Renal and urinary disorders
Urinary frequency
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Hepatobiliary disorders
Portal hypertension
|
2.6%
1/39 • Number of events 2 • 3 years, 6 months
|
|
Investigations
Aspartate aminotransferase increased -Transiminitis
|
2.6%
1/39 • Number of events 2 • 3 years, 6 months
|
|
Hepatobiliary disorders
Hepatobiliary disorders - other
|
5.1%
2/39 • Number of events 3 • 3 years, 6 months
|
|
Infections and infestations
Appendicitis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
Other adverse events
| Measure |
Panobinostat (PANO) Therapy
n=39 participants at risk
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.
|
|---|---|
|
Infections and infestations
Lung Infection
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Infections and infestations
Sinusitis
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
10.3%
4/39 • Number of events 4 • 3 years, 6 months
|
|
Cardiac disorders
Atrial fibrillation
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Infections and infestations
Encephalitis infection
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Infections and infestations
Sepsis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Psychiatric disorders
Confusion
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Psychiatric disorders
Hallucinations
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Investigations
Neutrophil count decreased
|
25.6%
10/39 • Number of events 12 • 3 years, 6 months
|
|
General disorders
Non-cardiac chest pain
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Investigations
Platelet count decreased
|
17.9%
7/39 • Number of events 9 • 3 years, 6 months
|
|
Metabolism and nutrition disorders
Anorexia
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Vascular disorders
Hypertension
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
General disorders
Fever
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Infections and infestations
Papulopustular rash
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Nervous system disorders
Headache
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Nervous system disorders
Syncope
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Nervous system disorders
Myelitis
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.3%
4/39 • Number of events 5 • 3 years, 6 months
|
|
Eye disorders
Floaters
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Investigations
Weight loss
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
General disorders
Edema limbs
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Renal and urinary disorders
Acute kidney injury
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Bullous dermatitis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Nervous system disorders
Akathisia
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Periorbital edema
|
5.1%
2/39 • Number of events 2 • 3 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Infections and infestations
Appendicitis
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
|
Immune system disorders
Immune system disorders -Other
|
2.6%
1/39 • Number of events 1 • 3 years, 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place