Japanese Phase 2 Study to Evaluate the Efficacy and Safety of Pomalidomide in Subjects With Relapsed and Refractory Multiple Myeloma

• Sponsor: Celgene Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02011113
• Collaborator: (none)
• Enrollment: 36
• Locations: 14
• Arm: 1
• Duration (Months): 21
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of pomalidomide in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pomalidomide; Drug: Dexamethasone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Single-arm, Open-label Study in Japan to Evaluate the Efficacy and Safety of Pomalidomide (CC-4047) in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pomalidomide plus dexamethasone	Drug: Pomalidomide; 4 mg oral pomalidomide once daily Days 1-21 of each 28-day cycle; Other Names: CC-4047 ; Drug: Dexamethasone; 40 mg or 20 mg oral dexamethasone once daily on Days 1, 8, 15, 22 of each 28-day cycle; Other Names: LenaDex

Outcome Measures

Primary Outcome Measures

1. Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria [From the first dose until the data cut-off date of 03 Sept 2014; Maximum time in follow-up was 36.0 weeks.]

   Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

2. Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria (Later Cut-off Date) [From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks]

   Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

Secondary Outcome Measures

1. Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria [From first dose until the data cut-off date of 03 September 2014; maximum time in follow-up was 36.0 weeks]

   Myeloma response was defined as a best overall response of complete response (CR) or partial response (PR) CR is defined as: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.

2. Time to Response [From the first dose until the data cut-off date of 03 September 2014. Maximum time on follow-up was 36.0 weeks.]

   Time to response was calculated as the time from the first dose to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.

3. Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria (Later Cut-off Date) [From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks]

   Myeloma response was defined as a best overall response of complete response (CR) or partial response (PR) CR is defined as: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.

4. Time to Response (Later Cut-off Date) [From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks]

   Time to response was calculated as the time from the first dose to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.

5. Kaplan-Meier Estimates of Duration of Response [From first dose until the data cut-off date of 03 September 2014; maximum time for follow-up was 36 weeks]

   Duration of response (calculated for responders only) was defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria.

6. Kaplan-Meier Estimates of Duration of Response (Later Cut-off Date) [From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks]

   Duration of response (calculated for responders only) was defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria.

7. Kaplan-Meier Estimates of Progression-free Survival (PFS) [From the first dose until the data cut-off date of 03 September 2014; maximum time on treatment was 36.0 weeks]

   PFS was calculated as the time from the first dosing to the first documented progressive disease, as determined by the investigators based on the IMWG Uniform Response criteria, or death, whichever occurred earlier

8. Kaplan-Meier Estimates of PFS (Later Cut-off Date) [From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks]

   PFS was calculated as the time from the first dosing to the first documented progressive disease, as determined by the investigators based on the IMWG Uniform Response criteria, or death, whichever occurred earlier

9. Number of Participants With Adverse Events [From first dose of study drug to final data cut-off date of 25 Sept 2015, maximum duration on treatment was 80.9 weeks]

   Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. Serious AEs (SAEs) were those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring on or after the first treatment of the study medication and within 28 days after the last dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Must be ≥ 20 years of age at the time of signing the informed consent document.

1. The subject must understand and voluntarily sign an informed consent document before any study related assessments/procedures are conducted.

2. Must be able to adhere to the study visit schedule and other protocol requirements.

3. Have a documented diagnosis of multiple myeloma and have relapsed and refractory disease. Subjects must have received at least 2 prior therapies. Subjects must have relapsed after having achieved at least stable disease for at least one cycle of treatment to at least one prior regimen and then developed progressive disease(PD). Subjects must also have documented evidence of progressive disease(PD) during or within 60 days (measured from the end of the last cycle) of completing treatment with the last antimyeloma drug regimen used just prior to study entry (refractory disease).

4. Subjects must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen).

5. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).

6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

8.Must agree to comply to pomalidomide Pregnancy Prevention Risk Management Plan.

Exclusion Criteria:

• 1. Pregnant or breastfeeding females 2. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone 3. ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy 4. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study 5. Any of the following laboratory abnormalities:

• Absolute neutrophil count < 1,000/µL

• Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells

• Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula

Cockcroft-Gault estimation of Creatinine Clearance:

• Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)

• Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior Red blood cell transfusion or recombinant human erythropoietin use is permitted)

• Serum glutamic oxaloacetic transaminase(SGOT)/aspartate aminitransferase(AST) or serum glutamic pyruvic transaminase(SGPT)/alanine aminotransferase(ALT) > 3.0 x upper limit of normal(ULN)

• Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or ≥ 3.0 x upper limit of normal (ULN) for subjects with hereditary benign hyperbilirubinemia.

1. Subjects with any one of the following:

• Congestive heart failure (New York Heart Association Class III or IV)

• Myocardial infarction within 12 months prior to starting study treatment

• Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris 7. Peripheral neuropathy ≥ Grade 2. 8. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 5 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) 9. Known infection with human immunodeficiency virus (HIV) antibody positive, hepatitis B virus surface antigen (HBsAg) positive or hepatitis C virus antibody (HCVAb) positive. If negative for hepatitis B virus surface antigen (HBsAg) but hepatitis B core antibody (HBcAb) and/or hepatitis B surface antibody (HBsAb) positive status, a hepatitis B virus DNA test will be performed and if positive the subject will be excluded.

1. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide.

2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

3. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

4. Any condition that confounds the ability to interpret data from the study. 14. Previous therapy with pomalidomide. 15. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment.

5. Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment.

6. Subjects who received any of the following within the last 14 days of initiation of study treatment:

• Plasmapheresis

• Major surgery (kyphoplasty is not considered major surgery)

• Radiation therapy

• Use of any antimyeloma drug therapy. 18. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment.

1. Subjects who are planning for or who are eligible for stem cell transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celgene Trial Site	Nagoya	Aichi	Japan	467-8602
2	Celgene Trial Site	Kamogawa	Chiba	Japan	298-8602
3	Celgene Trial Site	Mito	Ibaragi	Japan	311-3193
4	Celgene Trial Site	Isehara	Kanagawa	Japan	259-1193
5	Celgene Trial Site	Fukuoka		Japan	812-8582
6	Celgene Trial Site	Hiroshima		Japan	734-8551
7	Celgene Trial Site	Kyoto		Japan	602-8566
8	Celgene Trial Site	Niigata		Japan	951-8566
9	Celgene Trial Site	Okayama		Japan	701-1192
10	Celgene Trial Site	Osaka		Japan	543-8555
11	Celgene Trial Site	Tokyo		Japan	104-0045
12	Celgene Trial Site	Tokyo		Japan	150-8935
13	Celgene Trial Site	Tokyo		Japan	160-8582
14	Celgene Trial Site	Tokyo		Japan	162-8655

Sponsors and Collaborators

• Celgene Corporation

Investigators

• Study Director: Toru Sasaki, Director, Celgene K.K.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT02011113
• Other Study ID Numbers: CC-4047-MM-011
• First Posted: Dec 13, 2013
• Last Update Posted: Nov 1, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Celgene Corporation: Pomalidomide,; CC-4047,; Dexamethasone,; Relapsed and refractory multiple myeloma,; phase 2
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Pomalidomide

Study Results

Participant Flow

Recruitment Details	All study participants who were on pomalidomide were transferred to the post-marketing study and continued the study treatment when pomalidomide became commercially available.
Pre-assignment Detail	Treatment phase discontinuation occurred when a participant had confirmed progressive disease, development of unacceptable toxicity, voluntary withdrawal or met other criteria for treatment discontinuation.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Pomalidomide 4 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Dexamethasone 40 mg PO once daily on Days 1, 8, 15, 22 of each 28-day cycle for those who are ≤ 75 years of age Dexamethasone 20 mg PO once daily on Days 1, 8, 15, 22 of each 28-day cycle for those who are > 75 years of age
Period Title: Overall Study
STARTED	36
COMPLETED	0
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Pomalidomide: 4 mg oral pomalidomide once daily Days 1-21 of each 28-day cycle Dexamethasone: 40 mg or 20 mg oral dexamethasone once daily on Days 1, 8, 15, 22 of each 28-day cycle
Overall Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.5
Age, Customized (participants) [Number]
≤ 75 Years Old	32 88.9%
> 75 Years Old	4 11.1%
Sex: Female, Male (Count of Participants)
Female	20 55.6%
Male	16 44.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	36 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Time from first diagnosis (years) [Median (Full Range) ]
Median (Full Range) [years]	4.65
Durie-Salmon Multiple myeloma staging at screening (participants) [Number]
Stage I	7 19.4%
Stage II	16 44.4%
Stage III	13 36.1%
Eastern Cooperative Oncology Group Performance Status] (ECOG) (participants) [Number]
0 = (Asymptomatic)	17 47.2%
1 = (Symptomatic but completely ambulatory)	16 44.4%
2 = (Ambulatory but unable to work)	3 8.3%
3 = (Limited self-care)	0 0%
4 = (Completely disabled)	0 0%
Prior Chemotherapy Regimens (regimens) [Median (Full Range) ]
Median (Full Range) [regimens]	6.0
Prior Stem Cell Transplant for Myeloma (participants) [Number]
Yes	19 52.8%
No	17 47.2%
Durie-Salmon Multiple Myeloma staging at screening (participants) [Number]
Stage I	7 19.4%
Stage II	16 44.4%
Stage III	13 36.1%

Outcome Measures

1. Primary Outcome

Title	Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria
Description	Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Time Frame	From the first dose until the data cut-off date of 03 Sept 2014; Maximum time in follow-up was 36.0 weeks.

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants responding]	25.0 69.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pomalidomide Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments	Based on one sample binomial test for dichotomized response proportion against the null hypothesis(H0: p = 0.1)
	Method	Binomial test for dichotomized response
	Comments

2. Secondary Outcome

Title	Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria
Description	Myeloma response was defined as a best overall response of complete response (CR) or partial response (PR) CR is defined as: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.
Time Frame	From first dose until the data cut-off date of 03 September 2014; maximum time in follow-up was 36.0 weeks

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants responding]	22.2 61.7%

3. Secondary Outcome

Title	Time to Response
Description	Time to response was calculated as the time from the first dose to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.
Time Frame	From the first dose until the data cut-off date of 03 September 2014. Maximum time on follow-up was 36.0 weeks.

Outcome Measure Data

Analysis Population Description

Included participants with at least a PR or better based on Assessment using IMWG criteria.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	9
Median (Full Range) [weeks]	4.10

4. Primary Outcome

Title	Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria (Later Cut-off Date)
Description	Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Time Frame	From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population (EEP) includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants responding]	41.7 115.8%

5. Secondary Outcome

Title	Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria (Later Cut-off Date)
Description	Myeloma response was defined as a best overall response of complete response (CR) or partial response (PR) CR is defined as: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.
Time Frame	From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

Outcome Measure Data

Analysis Population Description

EEP includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants responding]	38.9 108.1%

6. Secondary Outcome

Title	Time to Response (Later Cut-off Date)
Description	Time to response was calculated as the time from the first dose to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.
Time Frame	From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

Outcome Measure Data

Analysis Population Description

Included participants with at least a PR or better based on Assessment using IMWG criteria; EPP includes all participants who meet eligibility criteria, take at least one dose of study medication, and have a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	15
Median (Full Range) [weeks]	8.10

7. Secondary Outcome

Title	Kaplan-Meier Estimates of Duration of Response
Description	Duration of response (calculated for responders only) was defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria.
Time Frame	From first dose until the data cut-off date of 03 September 2014; maximum time for follow-up was 36 weeks

Outcome Measure Data

Analysis Population Description

Duration of Response was not analyzed as there was insufficient data available at Cycle 2, Day 1 of study treatment. There was limited data evaluated and data were not analyzed.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	0

8. Secondary Outcome

Title	Kaplan-Meier Estimates of Duration of Response (Later Cut-off Date)
Description	Duration of response (calculated for responders only) was defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria.
Time Frame	From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	15
Median (95% Confidence Interval) [weeks]	NA

9. Secondary Outcome

Title	Kaplan-Meier Estimates of Progression-free Survival (PFS)
Description	PFS was calculated as the time from the first dosing to the first documented progressive disease, as determined by the investigators based on the IMWG Uniform Response criteria, or death, whichever occurred earlier
Time Frame	From the first dose until the data cut-off date of 03 September 2014; maximum time on treatment was 36.0 weeks

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	36
Median (95% Confidence Interval) [weeks]	19.0

10. Secondary Outcome

Title	Kaplan-Meier Estimates of PFS (Later Cut-off Date)
Description	PFS was calculated as the time from the first dosing to the first documented progressive disease, as determined by the investigators based on the IMWG Uniform Response criteria, or death, whichever occurred earlier
Time Frame	From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population includes all participants who met eligibility criteria, took at least one dose of study medication, and had a baseline and a post-baseline efficacy assessment.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.
Measure Participants	36
Median (95% Confidence Interval) [weeks]	32.10

11. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. Serious AEs (SAEs) were those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring on or after the first treatment of the study medication and within 28 days after the last dose.
Time Frame	From first dose of study drug to final data cut-off date of 25 Sept 2015, maximum duration on treatment was 80.9 weeks

Outcome Measure Data

Analysis Population Description

Safety population includes all participants who took at least one dose of study medication.

Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression or pomalidomide discontinuation for any reason.
Measure Participants	36
Any 1 TEAE	36 100%
TEAE related to any study drugs	33 91.7%
TEAE related to Pomalidomide	33 91.7%
TEAE related to Dexamethasone(Dex)	27 75%
TEAE with ≥ Grade (GR) 3	33 91.7%
≥ 1TEAE ≥ GR 3 related to any study drug	30 83.3%
TEAE ≥ GR 3 related to Pomalidomide	30 83.3%
TEAE ≥ GR 3 related to Dexamethasone	11 30.6%
≥ 1 serious TEAE	16 44.4%
Serious TEAE related to any study drug	8 22.2%
Serious TEAE related to Pomalidomide	8 22.2%
Serious TEAE related to Dexamethasone	6 16.7%
TEAE leading to stopping of any study drug	5 13.9%
TEAE leading to discontinuation of Pomalidomide	5 13.9%
TEAE leading to discontinuation of Dexamethasone	5 13.9%
Related TEAE leading to stopping of study drug	4 11.1%
Related TEAE leading to stopping of Pomalidomide	4 11.1%
Related TEAE leading to stopping Dexamethasone	4 11.1%
TEAE leading to dose reduction of any study drug	19 52.8%
TEAE leading to dose reduction of Pomalidomide	10 27.8%
TEAE leading to dose reduction of Dexamethasone	15 41.7%
TEA leading to dose interruption of any study drug	20 55.6%
TEAE leading to dose interruption of Pomalidomide	18 50%
TEAE leading to dose interruption of Dexamethasone	11 30.6%
Related TEAE leading to dose reduction of any drug	18 50%
Related TEAE causing a dose reduction Pomalidomide	10 27.8%
≥1 related TEAE causing a dose reduction: Dex	14 38.9%
Related TEAE leading to interruption of drugs	16 44.4%
Related TEAE causing an interruption Pomalidomide	15 41.7%
Related TEAE causing an interruption to Dex	8 22.2%
TEAE Grade 5	3 8.3%

Adverse Events

Time Frame	From the start of study drug through 28 days after the last dose of study drug. Maximum duration of study treatment was 80.9 weeks; up to 25 September 2015 data cut-off
Arm/Group Title	Pomalidomide Plus Dexamethasone
Arm/Group Description	Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression or pomalidomide discontinuation for any reason.
All Cause Mortality
	Pomalidomide Plus Dexamethasone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pomalidomide Plus Dexamethasone
	Affected / at Risk (%)	# Events
Total	16/36 (44.4%)
Blood and lymphatic system disorders
ANAEMIA	5/36 (13.9%)
NEUTROPENIA	2/36 (5.6%)
THROMBOCYTOPENIA	1/36 (2.8%)
Cardiac disorders
CARDIAC FAILURE	1/36 (2.8%)
Gastrointestinal disorders
CONSTIPATION	2/36 (5.6%)
General disorders
MULTI-ORGAN FAILURE	1/36 (2.8%)
PYREXIA	1/36 (2.8%)
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL	1/36 (2.8%)
Infections and infestations
PNEUMONIA	5/36 (13.9%)
PNEUMONIA PNEUMOCOCCAL	1/36 (2.8%)
BRONCHITIS	1/36 (2.8%)
MENINGITIS	1/36 (2.8%)
PNEUMOCYSTIS JIROVECII PNEUMONIA	1/36 (2.8%)
SEPSIS	1/36 (2.8%)
Injury, poisoning and procedural complications
SPINAL COMPRESSION FRACTURE	1/36 (2.8%)
Investigations
BLOOD FIBRINOGEN DECREASED	1/36 (2.8%)
C-REACTIVE PROTEIN INCREASED	1/36 (2.8%)
Metabolism and nutrition disorders
DECREASED APPETITE	1/36 (2.8%)
HYPONATRAEMIA	1/36 (2.8%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/36 (2.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	2/36 (5.6%)
Renal and urinary disorders
URINARY RETENTION	1/36 (2.8%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	2/36 (5.6%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/36 (2.8%)
HYPOXIA	1/36 (2.8%)
PLEURAL EFFUSION	1/36 (2.8%)
INTERSTITIAL LUNG DISEASE	1/36 (2.8%)
Vascular disorders
SHOCK HAEMORRHAGIC	1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	Pomalidomide Plus Dexamethasone
	Affected / at Risk (%)	# Events
Total	36/36 (100%)
Blood and lymphatic system disorders
NEUTROPENIA	26/36 (72.2%)
THROMBOCYTOPENIA	16/36 (44.4%)
ANAEMIA	17/36 (47.2%)
LYMPHOPENIA	8/36 (22.2%)
LEUKOPENIA	6/36 (16.7%)
Endocrine disorders
HYPOTHYROIDISM	2/36 (5.6%)
Gastrointestinal disorders
CONSTIPATION	9/36 (25%)
DIARRHOEA	7/36 (19.4%)
NAUSEA	7/36 (19.4%)
ABDOMINAL PAIN UPPER	2/36 (5.6%)
HAEMORRHOIDS	2/36 (5.6%)
PROCTALGIA	2/36 (5.6%)
VOMITING	2/36 (5.6%)
General disorders
PYREXIA	9/36 (25%)
OEDEMA PERIPHERAL	7/36 (19.4%)
MALAISE	6/36 (16.7%)
FATIGUE	4/36 (11.1%)
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL	3/36 (8.3%)
Immune system disorders
HYPOGAMMAGLOBULINAEMIA	2/36 (5.6%)
Infections and infestations
NASOPHARYNGITIS	9/36 (25%)
UPPER RESPIRATORY TRACT INFECTION	4/36 (11.1%)
BRONCHITIS	2/36 (5.6%)
PNEUMONIA	3/36 (8.3%)
HERPES ZOSTER	3/36 (8.3%)
CYSTITIS	2/36 (5.6%)
GASTROENTERITIS	2/36 (5.6%)
Pharyngitis	3/36 (8.3%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	2/36 (5.6%)
ASPARTATE AMINOTRANSFERASE INCREASED	2/36 (5.6%)
BLOOD ALKALINE PHOSPHATASE INCREASED	2/36 (5.6%)
WEIGHT DECREASED	2/36 (5.6%)
WEIGHT INCREASED	2/36 (5.6%)
Metabolism and nutrition disorders
DECREASED APPETITE	4/36 (11.1%)
HYPERURICAEMIA	4/36 (11.1%)
HYPOALBUMINAEMIA	4/36 (11.1%)
HYPERCALCAEMIA	2/36 (5.6%)
HYPERGLYCAEMIA	3/36 (8.3%)
HYPOCALCAEMIA	2/36 (5.6%)
HYPOKALAEMIA	4/36 (11.1%)
HYPONATRAEMIA	2/36 (5.6%)
HYPOPHOSPHATAEMIA	3/36 (8.3%)
DIABETES MELLITUS	2/36 (5.6%)
INCREASED APPETITE	2/36 (5.6%)
Musculoskeletal and connective tissue disorders
MYALGIA	3/36 (8.3%)
MUSCLE SPASMS	2/36 (5.6%)
Nervous system disorders
DYSGEUSIA	5/36 (13.9%)
HYPERSOMNIA	2/36 (5.6%)
PERIPHERAL SENSORY NEUROPATHY	2/36 (5.6%)
SOMNOLENCE	2/36 (5.6%)
HEADACHE	2/36 (5.6%)
NEUROPATHY PERIPHERAL	2/36 (5.6%)
TREMOR	2/36 (5.6%)
Psychiatric disorders
ANXIETY	3/36 (8.3%)
INSOMNIA	6/36 (16.7%)
RESTLESSNESS	2/36 (5.6%)
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	4/36 (11.1%)
HYPOXIA	3/36 (8.3%)
DYSPHONIA	2/36 (5.6%)
DYSPNOEA	2/36 (5.6%)
PLEURAL EFFUSION	2/36 (5.6%)
HICCUPS	2/36 (5.6%)
Skin and subcutaneous tissue disorders
RASH	7/36 (19.4%)
RASH MACULO-PAPULAR	3/36 (8.3%)
DECUBITUS ULCER	2/36 (5.6%)
Vascular disorders
HYPOTENSION	2/36 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Disclosure agreements varied; the Investigators shall not disclose any material/information disclosed by the Sponsor (Celgene KK) with the clinical trial or information obtained by conducting the clinical trial to third parties without Sponsor's prior written approval.