Trial Outcomes & Findings for Panobinostat (LBH589): Multiple Myeloma - Autologous Hematopoietic Cell Transplantation (HCT) (NCT NCT02722941)

Last Updated: 2022-11-01

Results Overview

Investigators will calculate RDI for each cohort. Relative dose intensity (RDI) represents the ratio of the amount of a drug actually delivered \[actual dose intensity (DI)\] to the amount planned (planned DI). The purpose of calculating RDI is to evaluate whether the planned DI of a chemotherapy treatment was actually achieved which may suggest the feasibility of planned treatment regimen. There are multitude of reports demonstrating a correlation between RDI and survival in cancer treatment. RDI = (total dose received by the patient = mg)/(planned full dose of drug = mg).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2022-11-01

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A: Maintenance Therapy Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
Overall Study STARTED	15	15
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Panobinostat (LBH589): Multiple Myeloma - Autologous Hematopoietic Cell Transplantation (HCT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome measures
Measure	Cohort A: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
Relative Dose Intensity (RDI) Per Cohort	97.9 percentage of dose Interval 77.1 to 100.0	89.6 percentage of dose Interval 63.1 to 100.0

SECONDARY outcome

Timeframe: Up to 5 years

Complete Response (CR) rate to panobinostat maintenance therapy after autologous HCT. CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow.

Outcome measures

Outcome measures
Measure	Cohort A: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
Complete Response Rate	73.33 percentage Interval 44.9 to 92.2	66.6 percentage Interval 38.4 to 88.2

SECONDARY outcome

Timeframe: at 2 years

Progressive Disease (PD) according to Uniform Response Reporting Criteria for Multiple Myeloma by the International Myeloma Working Group (IMWG). Increase of 25% from lowest response value in any of the following: * Serum M- component (absolute increase must be ≥ 0.5 g/dL) * Urine M-component (absolute increase must be ≥ 200 mg/24 h) * Only in patients without measurable serum and urine M protein levels and without measurable disease by free light chain (FLC) levels, bone marrow plasma cell percentage (absolute percentage must be ≥ 10% ) * Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas * Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder

Outcome measures

Outcome measures
Measure	Cohort A: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
Progression Free Survival (PFS)	71.8 percentage of participants Interval 41.1 to 88.4	53.3 percentage of participants Interval 26.3 to 74.4

SECONDARY outcome

Timeframe: at 2 years

OS: The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.

Outcome measures

Outcome measures
Measure	Cohort A: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 Participants Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
Overall Survival (OS)	100 percentage of participants first OS event occurred after 24 months	100 percentage of participants first OS event occurred after 24 months

Adverse Events

Cohort A: Maintenance Therapy

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Cohort B: Maintenance Therapy

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: Maintenance Therapy n=15 participants at risk Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 participants at risk Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
General disorders Flu like symptoms	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Colitis	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Nervous system disorders Headache	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
General disorders Fever	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Infections and infestations Lung infection	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Bone pain	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Cholecystitis	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.

Other adverse events

Additional Information

Taiga Nishihori, MD

Moffitt Cancer Center

Phone: 813-745-8156

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A: Maintenance Therapy n=15 participants at risk Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.	Cohort B: Maintenance Therapy n=15 participants at risk Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule. Panobinostat: Maintenance therapy dosing as outlined in Cohorts A and B.
Metabolism and nutrition disorders Hypercalcemia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations Creatinine increased	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Renal and urinary disorders Chronic kidney disease	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations Lymphocyte count decreased	26.7% 4/15 • Number of events 4 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations White blood cell decreased	40.0% 6/15 • Number of events 14 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	20.0% 3/15 • Number of events 5 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations Platelet count decreased	26.7% 4/15 • Number of events 6 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	26.7% 4/15 • Number of events 4 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Diarrhea	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Nervous system disorders Headache	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Vascular disorders Hypertension	33.3% 5/15 • Number of events 5 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	33.3% 5/15 • Number of events 5 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations Thrombocytopenia	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hyperglycemia	33.3% 5/15 • Number of events 6 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Blood and lymphatic system disorders Anemia	33.3% 5/15 • Number of events 5 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	33.3% 5/15 • Number of events 5 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Gastroesophageal reflux disease	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Back Pain	26.7% 4/15 • Number of events 4 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	20.0% 3/15 • Number of events 3 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Neck pain	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
General disorders Fatigue	33.3% 5/15 • Number of events 5 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Nervous system disorders Peripheral motor neuropathy	26.7% 4/15 • Number of events 4 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hypokalemia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations Cholesterol high	40.0% 6/15 • Number of events 6 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Infections and infestations Upper respiratory infection	26.7% 4/15 • Number of events 4 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hypophosphatemia	20.0% 3/15 • Number of events 6 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hypocalcemia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hyperkalemia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Bone pain	20.0% 3/15 • Number of events 3 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Nausea	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Respiratory, thoracic and mediastinal disorders Productive cough	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Fracture	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Renal and urinary disorders Polyuria and nocturia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations INR increased	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders -Other	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Hepatobiliary disorders Cholecystitis	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Cholecystectomy	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Investigations Neutrophil count decreased	26.7% 4/15 • Number of events 7 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Cardiac disorders Atrial fibrilation	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Arthalgia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Arthritis	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Psychiatric disorders Insomnia	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Nervous system disorders Fibromyalgia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hypertriglyceridemia	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	13.3% 2/15 • Number of events 2 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Metabolism and nutrition disorders Hypoglycemia	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Renal and urinary disorders Renal calculi	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.
Ear and labyrinth disorders Ottis externa	0.00% 0/15 • Adverse events collected from date of consent until off study date, 4 years, 2 months.	6.7% 1/15 • Number of events 1 • Adverse events collected from date of consent until off study date, 4 years, 2 months.