ACY-1215 (Ricolinostat) in Combination With Pomalidomide... | NCT01997840

Label	Type	Description	Intervention Names
ACY-1215 in combination with pomalidomide and dexamethasone	Experimental	ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone	Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone

Name	Type	Description	Arm Group Labels	Other Names
ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone	Drug	ACY-1215 (Ricolinostat) 160mg QD Days 1-21 with pomalidomide 4mg QD Days 1-21 and dexamethasone 40mg QD Days 1,8,15,22 of a 28-day cycle

Measure	Description	Time Frame
Maximum Tolerated Dose (MTD) of ACY-1215- Phase 1b	The maximum tolerated dose (MTD) was defined as the highest dose level at which no more than 1 of 6 patients experienced a dose-limiting toxicity (DLT) within the first 28-day cycle. If no more than 1 of these 6 patients experienced a DLT within the first 28-day cycle, then the last dose level enrolled to meet these criteria was identified as the recommended dose for the Phase 2 segment of the study.	From first dose until the end of Phase 1b (up to a maximum of approximately 50 weeks).
Overall Response Rate (ORR) Per Investigator - Phase 2	Overall response rate (ORR) is defined as the percentage of participants with a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR: No detectable myeloma cells in the bone marrow. Normal free light chain ratio. Absence of clonal cells in the bone marrow. CR: Negative immunofixation on the serum and urine. Disappearance of any soft tissue plasmacytomas. Less than 5% plasma cells in the bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis, or At least a 90% reduction in serum M-protein plus urine M-protein level less than 100 mg per 24 hours. PR: At least a 50% reduction in serum M-protein. Reduction in 24-hour urinary M-protein by at least 90% or to less than 200 mg per 24 hours. For patients with non-secretory myeloma, a reduction of at least 50% in the size of soft tissue plasmacytomas is required.	From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

Measure	Description	Time Frame
Time to Response (TTR)	Time to response (TTR) was defined as the time from first dose of study treatment to the first documentation of response (either partial response (PR) or complete response (CR)). CR: Negative immunofixation on the serum and urine. Disappearance of any soft tissue plasmacytomas. Less than 5% plasma cells in the bone marrow. PR: At least a 50% reduction in serum M-protein. Reduction in 24-hour urinary M-protein by at least 90% or to less than 200 mg per 24 hours. For patients with non-secretory myeloma, a reduction of at least 50% in the size of soft tissue plasmacytomas is required.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Must have a documented diagnosis of multiple myeloma and have relapsed-and-refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease (SD) for at least one cycle of treatment to at least one prior regimen and then developed progressive disease (PD). Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)
Must not be a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT
Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g/24 hours)
Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to, and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods,and Education and Counseling Guidance must be followed per protocol
Must be able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation. Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended. Coumadin will be allowed provided the patient is fully anticoagulated, with an international normalized ratio (INR) of 2 to 3

Exclusion Criteria:

Pregnant or lactating females
Prior therapy with HDAC inhibitor
Any of the following laboratory abnormalities:
- ANC < 1,000/µL
- Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; and < 50,000/ µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
- Hemoglobin < 8g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion is permitted)
- Creatine clearance < 45mL/min according to Cockcroft-Gault formula. If creatine clearance calculated from the 24-hour urine sample is ≥ 45 mL/min, patient will qualify for the study
- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST), or serum glutamic pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT) > 3.0 × ULN
- Serum total bilirubin > 2.0 mg/dL
Prior history of malignancies, other than MM, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix or breast
- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
Corrected QT interval using Fridericia's formula (QTcF) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)
Positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection
Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (such as Steven Johnson Syndrome). Hypersensitivity, such as rash, that can be medically managed is allowable
Peripheral neuropathy ≥ Grade 2 despite supportive therapy
Radiotherapy or systemic therapy (standard or an investigational or biologic anticancer agent) within 14 days of initiation of study drug treatment
Current enrollment in another clinical trial involving treatment and/or is receiving an investigational agent for any reason
Inability or unwillingness to comply with birth control requirements or regional REMS/RevAid programs

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Local Institution - 201		Boston	Massachusetts	02215	United States
Cleveland Clinic

Label	URL
BMS Clinical Trial Information	View source
BMS Clinical Trial Patient Recruiting	View source

ID	Title	Description
FG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
FG001	Phase 1b - ACY-1215 Dose Level 3

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 12, 2016

ID	Title	Description
BG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
BG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
BG002	Phase 2 - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
BG003	Phase 2 - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0014 BG00285 BG00311 BG004103

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD) of ACY-1215- Phase 1b

The maximum tolerated dose (MTD) was defined as the highest dose level at which no more than 1 of 6 patients experienced a dose-limiting toxicity (DLT) within the first 28-day cycle. If no more than 1 of these 6 patients experienced a DLT within the first 28-day cycle, then the last dose level enrolled to meet these criteria was identified as the recommended dose for the Phase 2 segment of the study.

All treated participants in Phase 1b. Prespecified to be reported as combined for Phase 1b only.

Posted

Number

mg/day

From first dose until the end of Phase 1b (up to a maximum of approximately 50 weeks).

ID	Title	Description
OG000	Phase 1b - ACY-1215	Participants received either 160 mg ACY-1215 once per day (Dose Level 1) or 160 mg ACY-1215 twice per day (Dose Level 3) and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Units	Counts
Participants	OG0007

Title

Denominators

Categories

Title	Measurements
	OG000320

Primary

Overall Response Rate (ORR) Per Investigator - Phase 2

Overall response rate (ORR) is defined as the percentage of participants with a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

sCR:

No detectable myeloma cells in the bone marrow.
Normal free light chain ratio.
Absence of clonal cells in the bone marrow.

CR:

Negative immunofixation on the serum and urine.
Disappearance of any soft tissue plasmacytomas.
Less than 5% plasma cells in the bone marrow.

VGPR:

Serum and urine M-protein detectable by immunofixation but not on electrophoresis, or
At least a 90% reduction in serum M-protein plus urine M-protein level less than 100 mg per 24 hours.

PR:

At least a 50% reduction in serum M-protein.
Reduction in 24-hour urinary M-protein by at least 90% or to less than 200 mg per 24 hours.
For patients with non-secretory myeloma, a reduction of at least 50% in the size of soft tissue plasmacytomas is required.

All treated participants in Phase 2 Efficacy evaluable population. Prespecified to be reported for Phase 2 only.

Posted

Number

95% Confidence Interval

Percent of Participants

From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

ID	Title	Description
OG000	Phase 2 - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Time to Response (TTR)

Time to response (TTR) was defined as the time from first dose of study treatment to the first documentation of response (either partial response (PR) or complete response (CR)).

CR:

Negative immunofixation on the serum and urine.
Disappearance of any soft tissue plasmacytomas.
Less than 5% plasma cells in the bone marrow.

PR:

At least a 50% reduction in serum M-protein.
Reduction in 24-hour urinary M-protein by at least 90% or to less than 200 mg per 24 hours.
For patients with non-secretory myeloma, a reduction of at least 50% in the size of soft tissue plasmacytomas is required.

All treated participants in the Efficacy Evaluable population with a best response of PR or CR.

Posted

Mean

Full Range

Weeks

From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Duration of Response (DoR)

Duration of Response (DOR) was defined as the time from first partial response (PR) or complete response (CR) to the first documentation of progressive disease (PD) or death.

PR:

>= 50% reduction in serum M-protein.
Reduction in 24-hour urinary M-protein by >= 90% or to less than 200 mg per 24 hours.
For non-secretory myeloma, a reduction of >= 50% in size of soft tissue plasmacytomas.

CR:

Negative immunofixation on the serum and urine.
Disappearance of any soft tissue plasmacytomas.
< 5% plasma cells in the bone marrow.

PD:

Increase of 25% or more from nadir in serum M-protein, absolute increase of >= 0.5 g/dL.
Increase of 25% or more from nadir in 24-hour urinary M-protein, absolute increase of >=200 mg/24 hours.
Increase of 25% or more in the percentage of bone marrow plasma cells, absolute increase of >=10%.

Calculated using Kaplan-Meier estimates.

All treated participants in the Efficacy Evaluable population with a best response of PR or CR.

Posted

Median

95% Confidence Interval

Weeks

From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3

Secondary

Time to Progression (TTP)

Time to progression (TTP) was defined as the time from the date of first dose to the date of first documentation of progressive disease (PD).

PD:

Increase of 25% or more from nadir in serum M-protein, absolute increase of >= 0.5 g/dL.
Increase of 25% or more from nadir in 24-hour urinary M-protein, absolute increase of >=200 mg/24 hours.
Increase of 25% or more in the percentage of bone marrow plasma cells, absolute increase of >=10%.
New bone lesions or soft tissue plasmacytomas or increase size of existing bone lesions or soft tissue plasmacytomas.
Hypercalcemia attributed to myeloma.

All treated participants in the Efficacy Evaluable population who had PD.

Posted

Mean

Full Range

Weeks

From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Progression-free Survival (PFS)

Progression-free survival (PFS) was defined as the time from first dose of study treatment to the first documentation of progressive disease (PD) or death from any cause during study

PD:

Increase of 25% or more from nadir in serum M-protein, absolute increase of >= 0.5 g/dL.
Increase of 25% or more from nadir in 24-hour urinary M-protein, absolute increase of >=200 mg/24 hours.
Increase of 25% or more in the percentage of bone marrow plasma cells, absolute increase of >=10%.
New bone lesions or soft tissue plasmacytomas or increase size of existing bone lesions or soft tissue plasmacytomas.
Hypercalcemia attributed to myeloma. Calculated using Kaplan-Meier estimates.

All treated participants in the Efficacy Evaluable population.

Posted

Median

95% Confidence Interval

Weeks

From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Overall Response Rate (ORR) Per Central Adjudication Committee

Overall response rate (ORR) per Central Adjudication Committee is the percentage of participants with a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

sCR:

No detectable myeloma cells in the bone marrow.
Normal free light chain ratio.
Absence of clonal cells in the bone marrow.

CR:

Negative immunofixation on the serum and urine.
Disappearance of any soft tissue plasmacytomas.
Less than 5% plasma cells in the bone marrow.

VGPR:

Serum and urine M-protein detectable by immunofixation but not on electrophoresis, or
At least a 90% reduction in serum M-protein plus urine M-protein level less than 100 mg per 24 hours.

PR:

At least a 50% reduction in serum M-protein.
Reduction in 24-hour urinary M-protein by at least 90% or to less than 200 mg per 24 hours.
For patients with non-secretory myeloma, a reduction of at least 50% in the size of soft tissue plasmacytomas is required

All treated participants in the Efficacy Evaluable population. Data not collected.

Posted

From first dose until disease progression, study drug toxicity, end of study, or death due to any cause (up to approximately 120 months).

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001

Secondary

Number of Participants With Adverse Events (AEs)

An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.

All treated participants in the Safety population.

Posted

Count of Participants

Participants

From first dose until 30 days after last dose of study drug (assessed for an average of approximately 55 weeks to a maximum of approximately 456 weeks)

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Number of Participants With Serious Adverse Events (SAEs)

A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that:

Results in death;
Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE);
Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay).
Results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions);
Is a congenital anomaly/birth defect;
Constitutes an important medical event. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.

All treated participants in the Safety population.

Posted

Count of Participants

Participants

From first dose until 30 days after last dose of study drug (assessed for an average of approximately 55 weeks to a maximum of approximately 456 weeks)

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Number of Participants With Adverse Events (AEs) Leading to Discontinuation

All treated participants in the Safety population.

Posted

Count of Participants

Participants

From first dose until 30 days after last dose of study drug (assessed for an average of approximately 55 weeks to a maximum of approximately 456 weeks)

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Number of Participants With Adverse Events (AEs) Related to Study Drug

All treated participants in the Safety population.

Posted

Count of Participants

Participants

From first dose until 30 days after last dose of study drug (assessed for an average of approximately 55 weeks to a maximum of approximately 456 weeks)

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Secondary

Plasma Levels of ACY-1215 and Pomalidomide - Phase 1b

All treated participants with available PK results. Prespecified to be reported for Phase 1b only. Data not collected.

Posted

Cycle 1 day 1, Cycle 1 Day 2, Cycle 1 Day 8

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Anti-Drug Antibodies (ADA) - Phase 1b

All treated participants with available ADA results. Prespecified to be reported for Phase 1b only. Data not collected.

Posted

Cycle 1 day 1, Cycle 1 Day 2, Cycle 1 Day 8

ID	Title	Description
OG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.
OG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG0030 affected11 at risk
Neutropenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Atrial fibrillation	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Atrioventricular block complete	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Bradycardia	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Cardiac failure chronic	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Cardiac failure congestive	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Coronary artery occlusion	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Nausea	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Vomiting	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Chest pain	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
General physical health deterioration	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Sudden death	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Drug hypersensitivity	Immune system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Bronchitis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Cellulitis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Corona virus infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Escherichia sepsis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Haemophilus infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Implant site infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Influenza	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Lower respiratory tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Meningitis bacterial	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Pneumonia	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0026 affected85 at risk EG003
Pneumonia parainfluenzae viral	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Pneumonia viral	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Respiratory tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Sepsis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Septic shock	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Streptococcal bacteraemia	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Upper respiratory tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Urinary tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Urosepsis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Lumbar vertebral fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
White blood cell count decreased	Investigations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Dehydration	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Tumour lysis syndrome	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Acute lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Cholangiocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Cerebrovascular accident	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Embolic stroke	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Radiculopathy	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Spinal cord compression	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Confusional state	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Delirium	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Haematuria	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Renal failure	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Renal failure acute	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Aortic aneurysm	Vascular disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG00231 affected85 at risk EG0032 affected11 at risk
Febrile neutropenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Leukopenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Neutropenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00229 affected85 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00217 affected85 at risk EG003
Atrial fibrillation	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Cardiac failure congestive	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Palpitations	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Sinus bradycardia	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Sinus tachycardia	Cardiac disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0021 affected85 at risk EG003
Tricuspid valve disease	Cardiac disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Deafness	Ear and labyrinth disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Ear pain	Ear and labyrinth disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Tinnitus	Ear and labyrinth disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Cushingoid	Endocrine disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Cataract	Eye disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Dacryostenosis acquired	Eye disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Diplopia	Eye disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Dry eye	Eye disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Ectropion	Eye disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Lacrimation increased	Eye disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Vision blurred	Eye disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0023 affected85 at risk EG003
Abdominal distension	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0027 affected85 at risk EG003
Abdominal pain	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0027 affected85 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0026 affected85 at risk EG003
Aphthous stomatitis	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Constipation	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0013 affected4 at risk EG00214 affected85 at risk EG003
Diarrhoea	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0014 affected4 at risk EG00232 affected85 at risk EG003
Dyspepsia	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Dysphagia	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Flatulence	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Gastrointestinal disorder	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Gingival pain	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Nausea	Gastrointestinal disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG00219 affected85 at risk EG003
Oral disorder	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Oral pain	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Sensitivity of teeth	Gastrointestinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Vomiting	Gastrointestinal disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0029 affected85 at risk EG003
Asthenia	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0027 affected85 at risk EG003
Chest discomfort	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Chest pain	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0024 affected85 at risk EG003
Chills	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0024 affected85 at risk EG003
Fatigue	General disorders	16.1	Systematic Assessment	EG0002 affected3 at risk EG0012 affected4 at risk EG00249 affected85 at risk EG003
Feeling jittery	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Influenza like illness	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0025 affected85 at risk EG003
Instillation site pain	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0024 affected85 at risk EG003
Local swelling	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Oedema	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0025 affected85 at risk EG003
Oedema peripheral	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00213 affected85 at risk EG003
Pyrexia	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00218 affected85 at risk EG003
Vessel puncture site bruise	General disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Hypogammaglobulinaemia	Immune system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Bronchitis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0023 affected85 at risk EG003
Gastroenteritis	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Herpes simplex	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Herpes virus infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Influenza	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Localised infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Pneumonia	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0028 affected85 at risk EG003
Upper respiratory tract infection	Infections and infestations	16.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG00221 affected85 at risk EG003
Urinary tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0026 affected85 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Fall	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0022 affected85 at risk EG003
Periorbital contusion	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Scar	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Alanine aminotransferase increased	Investigations	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0027 affected85 at risk EG003
Aspartate aminotransferase increased	Investigations	16.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected4 at risk EG0026 affected85 at risk EG003
Blood alkaline phosphatase increased	Investigations	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Blood cholesterol increased	Investigations	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Blood creatinine increased	Investigations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0027 affected85 at risk EG003
Blood glucose increased	Investigations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Gamma-glutamyltransferase increased	Investigations	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Haematocrit decreased	Investigations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Haemoglobin decreased	Investigations	16.1	Systematic Assessment	EG0003 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Lymphocyte count decreased	Investigations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Neutrophil count decreased	Investigations	16.1	Systematic Assessment	EG0002 affected3 at risk EG0011 affected4 at risk EG00212 affected85 at risk EG003
Platelet count decreased	Investigations	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0026 affected85 at risk EG003
Weight decreased	Investigations	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
White blood cell count decreased	Investigations	16.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0029 affected85 at risk EG003
Dehydration	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0022 affected85 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0027 affected85 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected85 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0025 affected85 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00211 affected85 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0023 affected85 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0002 affected3 at risk EG0011 affected4 at risk EG0027 affected85 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0027 affected85 at risk EG003
Polydipsia	Metabolism and nutrition disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00213 affected85 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Arthropathy	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00213 affected85 at risk EG003
Bone disorder	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00211 affected85 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00217 affected85 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0029 affected85 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Osteoporosis	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0029 affected85 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Tenosynovitis	Musculoskeletal and connective tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Balance disorder	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Dizziness	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00211 affected85 at risk EG003
Dizziness postural	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Dysgeusia	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00211 affected85 at risk EG003
Headache	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0027 affected85 at risk EG003
Hypoaesthesia	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Memory impairment	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Neuropathy peripheral	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0024 affected85 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected85 at risk EG003
Somnolence	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected85 at risk EG003
Syncope	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Tremor	Nervous system disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00210 affected85 at risk EG003
VIth nerve paralysis	Nervous system disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Anxiety	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Confusional state	Psychiatric disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Delirium	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Depression	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0026 affected85 at risk EG003
Insomnia	Psychiatric disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00216 affected85 at risk EG003
Mood altered	Psychiatric disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Renal failure	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Renal failure acute	Renal and urinary disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0022 affected85 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected85 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG00215 affected85 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0028 affected85 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0029 affected85 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0028 affected85 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0024 affected85 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0028 affected85 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0025 affected85 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0023 affected85 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0024 affected85 at risk EG003
Actinic keratosis	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Hair growth abnormal	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Hair texture abnormal	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0025 affected85 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0022 affected85 at risk EG003
Rash	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG00210 affected85 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0021 affected85 at risk EG003
Skin disorder	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Swelling face	Skin and subcutaneous tissue disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected85 at risk EG003
Aortic arteriosclerosis	Vascular disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Flushing	Vascular disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0025 affected85 at risk EG003
Hypertension	Vascular disorders	16.1	Systematic Assessment	EG0002 affected3 at risk EG0010 affected4 at risk EG0022 affected85 at risk EG003
Hypotension	Vascular disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0023 affected85 at risk EG003
Orthostatic hypotension	Vascular disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003
Peripheral coldness	Vascular disorders	16.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected85 at risk EG003

ID	Term
D009101	Multiple Myeloma
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D001796	Blood Protein Disorders
D006402	Hematologic Diseases

ID	Term
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
C572255	ricolinostat
C467566	pomalidomide
D003907	Dexamethasone

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1b - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.	2	3	0	3	3	3
EG001	Phase 1b - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.	1	4	2	4	4	4
EG002	Phase 2 - ACY-1215 Dose Level 1	Participants received 160 mg ACY-1215 and 4 mg pomalidomide daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.	39	85	37	85	82	85
EG003	Phase 2 - ACY-1215 Dose Level 3	Participants received 160 mg ACY-1215 twice daily in combination with 4 mg pomalidomide once daily on Days 1-21 of each 28-day cycle. Participants also received 40 mg (<=75 years) or 20 mg (>75 years) dexamethasone on Days 1, 8, 15, and 22 of each 28-day treatment cycle.	3	11	7	11	11	11