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

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02722941
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 77.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to learn more about ways to prevent or delay relapse of multiple myeloma (MM). This study will determine the best dosing schedule of LBH589 maintenance therapy as well as the safety (side effects) and tolerability of LBH589 maintenance therapy after autologous hematopoietic cell transplant (HCT).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Panobinostat	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Panobinostat (LBH589) as Maintenance Therapy in Multiple Myeloma Following Autologous Hematopoietic Cell Transplantation
• Actual Study Start Date: Jun 10, 2016
• Actual Primary Completion Date: Jun 7, 2020
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cohort A: Maintenance Therapy Panobinostat (LBH589): 20 mg by mouth three (3) times per week, every other week, of a 28-day schedule.	Drug: Panobinostat; Maintenance therapy dosing as outlined in Cohorts A and B.; Other Names: LBH589
Active Comparator: Cohort B: Maintenance Therapy Panobinostat (LBH589): 10 mg by mouth daily for seven (7) days, every other week, of a 28-day schedule.	Drug: Panobinostat; Maintenance therapy dosing as outlined in Cohorts A and B.; Other Names: LBH589

Outcome Measures

Primary Outcome Measures

1. Relative Dose Intensity (RDI) Per Cohort [Up to 2 years]

   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).

Secondary Outcome Measures

1. Complete Response Rate [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.

2. Progression Free Survival (PFS) [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

3. Overall Survival (OS) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients, age ≥ 18 years old

• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

• Histologically confirmed diagnosis of multiple myeloma

• Meeting the Criteria for Symptomatic Multiple Myeloma (CRAB criteria) before the initiation of systemic chemotherapy

• Received high-dose melphalan (≥ 140 mg/m^2) followed by autologous HCT based on the institutional guidelines and within +45 and +180 after autologous HCT at the time of panobinostat maintenance initiation

• Must have achieved at least partial response (PR) prior to autologous HCT and must not have progressive disease (PD) prior to the initiation of maintenance therapy

• Must meet the following laboratory criteria (prior to the initiation of panobinostat maintenance): Absolute neutrophil count (ANC) ≥ 1 x 10^{9/L; Hemoglobin ≥ 8 g/dl; Platelets ≥ 50 x 10}9/L (without transfusion support); Creatinine clearance ≥ 40 ml/min or serum creatinine ≤ 2.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum bilirubin ≤ 1.5 x ULN; Albumin > 3.0 g/dl; Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

• Baseline (pre-HCT) multigated acquisition (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the limit of normal (LLN) of the institutional normal

• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 or Karnofsky performance status ≥ 70%

• Prior histone deacetylase (HDAC), deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer is allowed

Exclusion Criteria:

• Potential participants who have purely non-secretory multiple myeloma (i.e., the absence of a measurable protein in serum by electrophoresis and immunofixation and the absence of Bence-Jones protein in the urine defined by use of electrophoresis and immunofixation)

• Prior allogeneic HCT

• Prior solid organ transplant requiring immunosuppressive therapy

• Potential participants who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment

• Impaired cardiac function or clinically significant cardiac diseases

• Diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2

• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol

• Using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug

• Have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.

• Have received either immunotherapy within < 8 weeks; chemotherapy within < 4 weeks; or radiation therapy to > 30% of marrow-bearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies

• Have undergone major surgery ≤ 4 weeks prior to starting study drug or have not recovered from side effects of such therapy

• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP must have a negative serum pregnancy test within 24 hours of receiving the first dose of study medication.

• Male patients whose sexual partners are WOCBP not using effective birth control

• A prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)

• Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required

• Any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Taiga Nishihori, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 13, 2017

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT02722941
• Other Study ID Numbers: MCC-18430; CLBH589DUS97T
• First Posted: Mar 30, 2016
• Last Update Posted: Jun 2, 2022
• Last Verified: May 1, 2022

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: autologous hematopoietic cell transplant (HCT); autologous
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Panobinostat

Study Results

Participant Flow

Arm/Group Title	Cohort A: Maintenance Therapy	Cohort B: Maintenance Therapy
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cohort A: Maintenance Therapy	Cohort B: Maintenance Therapy	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 73.3%	8 53.3%	19 63.3%
>=65 years	4 26.7%	7 46.7%	11 36.7%
Sex: Female, Male (Count of Participants)
Female	6 40%	5 33.3%	11 36.7%
Male	9 60%	10 66.7%	19 63.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 20%	0 0%	3 10%
Not Hispanic or Latino	12 80%	15 100%	27 90%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 13.3%	2 13.3%	4 13.3%
White	13 86.7%	13 86.7%	26 86.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Relative Dose Intensity (RDI) Per Cohort
Description	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).
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A: Maintenance Therapy	Cohort B: Maintenance Therapy
Arm/Group Description	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.	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.
Measure Participants	15	15
Median (Full Range) [percentage of dose]	97.9	89.6

2. Secondary Outcome

Title	Complete Response Rate
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A: Maintenance Therapy	Cohort B: Maintenance Therapy
Arm/Group Description	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.	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.
Measure Participants	15	15
Number (95% Confidence Interval) [percentage]	73.33	66.6

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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
Time Frame	at 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A: Maintenance Therapy	Cohort B: Maintenance Therapy
Arm/Group Description	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.	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.
Measure Participants	15	15
Median (95% Confidence Interval) [percentage of participants]	71.8 478.7%	53.3 355.3%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	at 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A: Maintenance Therapy	Cohort B: Maintenance Therapy
Arm/Group Description	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.	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.
Measure Participants	15	15
Median (95% Confidence Interval) [percentage of participants]	100 666.7%	100 666.7%

Adverse Events

Time Frame	Adverse events collected from date of consent until off study date, 4 years, 2 months.
Arm/Group Title	Cohort A: Maintenance Therapy		Cohort B: Maintenance Therapy
Arm/Group Description	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.		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.
All Cause Mortality
	Cohort A: Maintenance Therapy		Cohort B: Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Cohort A: Maintenance Therapy		Cohort B: Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		3/15 (20%)
Gastrointestinal disorders
Colitis	1/15 (6.7%)	1	0/15 (0%)	0
Cholecystitis	1/15 (6.7%)	1	0/15 (0%)	0
General disorders
Flu like symptoms	0/15 (0%)	0	1/15 (6.7%)	1
Fever	0/15 (0%)	0	1/15 (6.7%)	1
Infections and infestations
Lung infection	0/15 (0%)	0	2/15 (13.3%)	2
Musculoskeletal and connective tissue disorders
Bone pain	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Headache	1/15 (6.7%)	1	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort A: Maintenance Therapy		Cohort B: Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/15 (66.7%)		11/15 (73.3%)
Blood and lymphatic system disorders
Anemia	5/15 (33.3%)	5	5/15 (33.3%)	5
Cardiac disorders
Atrial fibrilation	1/15 (6.7%)	1	0/15 (0%)	0
Ear and labyrinth disorders
Ottis externa	0/15 (0%)	0	1/15 (6.7%)	1
Gastrointestinal disorders
Diarrhea	2/15 (13.3%)	2	2/15 (13.3%)	2
Gastroesophageal reflux disease	2/15 (13.3%)	2	2/15 (13.3%)	2
Nausea	1/15 (6.7%)	1	1/15 (6.7%)	1
Cholecystectomy	1/15 (6.7%)	1	0/15 (0%)	0
Vomiting	0/15 (0%)	0	1/15 (6.7%)	1
General disorders
Fatigue	5/15 (33.3%)	5	2/15 (13.3%)	2
Hepatobiliary disorders
Cholecystitis	1/15 (6.7%)	1	0/15 (0%)	0
Infections and infestations
Upper respiratory infection	4/15 (26.7%)	4	0/15 (0%)	0
Investigations
White blood cell decreased	6/15 (40%)	14	3/15 (20%)	5
Platelet count decreased	4/15 (26.7%)	6	4/15 (26.7%)	4
Thrombocytopenia	0/15 (0%)	0	1/15 (6.7%)	1
Creatinine increased	1/15 (6.7%)	1	0/15 (0%)	0
Lymphocyte count decreased	4/15 (26.7%)	4	1/15 (6.7%)	1
Cholesterol high	6/15 (40%)	6	0/15 (0%)	0
INR increased	1/15 (6.7%)	1	0/15 (0%)	0
Neutrophil count decreased	4/15 (26.7%)	7	0/15 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	5/15 (33.3%)	6	2/15 (13.3%)	2
Hypercalcemia	1/15 (6.7%)	1	0/15 (0%)	0
Hypokalemia	1/15 (6.7%)	1	0/15 (0%)	0
Hypophosphatemia	3/15 (20%)	6	1/15 (6.7%)	1
Hypocalcemia	1/15 (6.7%)	1	0/15 (0%)	0
Hyperkalemia	1/15 (6.7%)	1	1/15 (6.7%)	1
Hypertriglyceridemia	0/15 (0%)	0	2/15 (13.3%)	2
Hypoglycemia	1/15 (6.7%)	1	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	4/15 (26.7%)	4	3/15 (20%)	3
Neck pain	1/15 (6.7%)	1	0/15 (0%)	0
Bone pain	3/15 (20%)	3	1/15 (6.7%)	1
Fracture	1/15 (6.7%)	1	0/15 (0%)	0
Musculoskeletal and connective tissue disorders -Other	1/15 (6.7%)	1	0/15 (0%)	0
Arthalgia	1/15 (6.7%)	1	0/15 (0%)	0
Arthritis	2/15 (13.3%)	2	0/15 (0%)	0
Osteoporosis	0/15 (0%)	0	1/15 (6.7%)	1
Myalgia	0/15 (0%)	0	1/15 (6.7%)	1
Nervous system disorders
Headache	1/15 (6.7%)	1	0/15 (0%)	0
Peripheral motor neuropathy	4/15 (26.7%)	4	2/15 (13.3%)	2
Peripheral sensory neuropathy	0/15 (0%)	0	1/15 (6.7%)	1
Fibromyalgia	1/15 (6.7%)	1	0/15 (0%)	0
Psychiatric disorders
Insomnia	2/15 (13.3%)	2	2/15 (13.3%)	2
Renal and urinary disorders
Chronic kidney disease	1/15 (6.7%)	1	0/15 (0%)	0
Polyuria and nocturia	1/15 (6.7%)	1	0/15 (0%)	0
Renal calculi	0/15 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Productive cough	1/15 (6.7%)	1	0/15 (0%)	0
Vascular disorders
Hypertension	5/15 (33.3%)	5	5/15 (33.3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.