Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01324947
• Collaborator: (none)
• Enrollment: 74
• Locations: 91
• Arm: 1
• Actual Duration (Months): 41
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of pomalidomide monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in study CC-4047-MM-003 (NCT01311687) and discontinued treatment with high-dose dexamethasone due to disease progression.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: pomalidomide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Multi-center, Single Arm Study For The Safety And Efficacy Of Pomalidomide Monotherapy For Subjects With Refractory Or Relapsed And Refractory Multiple Myeloma. A Companion Study For Clinical Trial CC-4047-MM003
• Actual Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jul 31, 2014
• Actual Study Completion Date: Jul 31, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pomalidomide Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity	Drug: pomalidomide; Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity; Other Names: CC-4047

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment [From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.]

   Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment. 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. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Secondary Outcome Measures

1. Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment [From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.]

   Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following: 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.

2. Number of Participants With Adverse Events and Type of Adverse Events [From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.]

   An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: Results in death; Is life-threatening; Requires or prolongs existing inpatient hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death

3. Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG [From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.]

   Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl) Urine M-component (absolute increase ≥ 200 mg/24 hours) In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) Bone marrow plasma cell percentage (absolute % ≥ 10%) Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.

4. Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria [From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to progression follow-up was 90.3 weeks.]

   Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl) Urine M-component (absolute increase ≥ 200 mg/24 hours) In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) Bone marrow plasma cell percentage (absolute % ≥ 10%) Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

5. Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria [From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum duration of response follow-up was 90.3 weeks.]

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

6. Kaplan-Meier Estimate for Overall Survival [From randomization through the follow-up phase; Maximum time on follow-up was 141.1 weeks.]

   Overall survival was calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

7. Time to Response Based on IMWG and Assessed by the Investigator [From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to response was 23.1 weeks]

   Time to Response was calculated as the time from enrollment to the initial response (PR or better) based on IMWG and assessed by the investigator.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in Study CC-4047-MM-003 and discontinued study therapy with dexamethasone alone (Treatment Arm B) after at least starting the second cycle of dexamethasone treatment and due to development of documented disease progression according to the International Myeloma Working Group (IMWG) criteria and as decided by an Independent Review Adjudication Committee (IRAC).

2. Must be ≥ 18 years at the time of signing the informed consent form.

3. The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. The only exception is if a skeletal survey was performed within 90 days prior to the start of Cycle 1, then a new survey will not be required.

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

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

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

7. Females of childbearing potential (FCBP†) must agree to utilize two reliable forms of contraception simultaneously or practice true abstinence [when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception]from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe.

8. Females must agree to abstain from breastfeeding during study participation and 28 days after study discontinuation.

9. Males must agree to either use a latex condom during any sexual contact with FCBP or practice true abstinence [when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception] while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy. .

10. Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study treatment.

11. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.

12. All subjects must agree not to share study medication

Exclusion Criteria

• The presence of any of the following will exclude a subject from enrollment:

1. Subjects with multiple myeloma who were not treated as a part of Study CC-4047-MM-003 (Arm B).

2. Subjects who received any anti-myeloma or anti-cancer therapies within the last 14 days of wash-out period before initiation of study treatment.

3. Subjects who discontinued CC-4047-MM-003 study ≥120 days.

4. Subjects who initiate another anti-myeloma therapy from the time of disease progression on study CC-4047-MM-003 to the time of treatment initiation in the companion study.

5. Any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) < 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 (If creatinine clearance calculated from the 24-hour urine sample is ≥45 ml/min, patient will qualify for the trial)

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

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

• Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)

• Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects with hereditary benign hyperbilirubinaemia

1. Prior history of malignancies, other than Multiple Myeloma (MM), 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)

1. Hypersensitivity to thalidomide or lenalidomide. (This includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy).

2. Peripheral neuropathy ≥ Grade 2.

3. 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.

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

5. Subjects with any one of the following:

• Congestive heart failure (NY 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

1. 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

1. Use of any investigational agents within 28 days or 5 half lives (whichever is longer) of treatment.

2. Subjects with chronic conditions such as rheumatoid arthritis, multiple sclerosis and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment.

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

5. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.

6. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

7. Pregnant or breastfeeding females.

8. Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B or C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Adelaide Hospital - SA Pathology Haematology	Adelaide		Australia	5000
2	Princess Alexandra Hospital - Haematology	Brisbane		Australia	4102
3	Royal Prince Alfred Hospital - Institute of Haematology	Camperdown		Australia	2050
4	Peter McCallum Cancer Institute - Directorate of Cancer Medicine	East Melbourne		Australia	3002
5	Frankston Hospital-Peninsula Health - Oncology Day Unit	Frankston		Australia	3199
6	The Alfred Hospital - Malignant Haematology & Stem Cell Transplantation	Melbourne		Australia	3004
7	Calvary Mater Newcastle - Haematology	Waratah		Australia	2298
8	Border Medical Oncology	Wodonga		Australia	3690
9	Wollongong Hospital - Haematology	Wollongong		Australia	2500
10	UZ Gent - Hematology	Gent		Belgium	9000
11	University Hospital Leuven - Hematology	Leuven		Belgium	3000
12	Cliniques Universitaires ULC de Mont-Godinne - Hematology	Yvoir		Belgium	5530
13	Tom Baker Cancer Center	Calgary	Alberta	Canada	T2N 4N2
14	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
15	British Columbia Cancer Agency, Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 1M9
16	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
17	London Health Sciences Centre	London	Ontario	Canada	N6A 5W9
18	Princess Margaret Hospital, University Health Network	Toronto	Ontario	Canada	M5G 2M9
19	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4
20	Royal Victoria Hospital	Montreal	Quebec	Canada	H3A1 A1
21	Charles University Hospital - Internal Medicine	Prague		Czechia	12808
22	Aalborg Sygemus - Haematology	Aalborg		Denmark	9000
23	Aarhus University Hospital	Aarhus		Denmark	8000
24	Odense University Hospital	Odense		Denmark	5000
25	Vejle Hospital - Hematology	Vejle		Denmark	7100
26	CHU Angers - Service des maladies du sang	Angers		France	49033
27	Centre Hospitalier de la côte basque - Hematologie	Bayonne		France	64019
28	Centre Hospitalier Départemental Vendée - Onco-hematologie	La Roche		France	85925
29	CHRU de Lille - Service des maladies du sang	Lille		France	59037
30	Institut Paoli Calmette - Hematology 1	Marseille		France	13009
31	CHU Hôtel-Dieu - Hematologie	Nantes		France	44093
32	Hôpital Saint Louis - Immuno-hematologie	Paris		France	75010
33	CHU Saint Antoine - Service des maladies du sang	Paris		France	75012
34	CHRU - Hôpital du Haut Lévêque - Centre François Magendie Service des maladies du sang	Pessac		France	33604
35	Centre Hospitalier Lyon sud - Hematologie	Pierre-Benite		France	69495
36	CHRU Hôpital Purpan - Hematologie	Toulouse		France	31059
37	Hôpital Bretonneau - Hématologie & Thérapie cellulaire	Tours		France	37044
38	CHU Nancy - Hematologie	Vandoeuvre-les-Nancy		France	54511
39	Universitatsklinikum Carl Gustav Carus-Medizinische Klinik und Poliklinik I	Dresden		Germany	01307
40	Universitätsklinikum Essen, Klinik für Hämatologie Westdeutsches Tumorzentrum	Essen		Germany	45122
41	Askepios Klinik Altona-Abteilung Hamatologie und Internistische Onkologie	Hamburg		Germany	22763
42	Universitätsklinikum Heidelberg - Medizinische Klinik und Poliklinik V	Heidelberg		Germany	69120
43	Universitätsklinikum Jena - Klinik fur Innere Medizin II-Hamatologie/Onkologie	Jena		Germany	07740
44	Universitätsklinikum Leipzig - Medizinische Klinik und Poliklinik II	Leipzig		Germany	04103
45	Universitätsklinikum Münster - Medizinische Klinik und Poliklinik A	Münster		Germany	48149
46	Universitätsklinikum Tübingen - Medizinische Klinik und Poliklinik - Abteilung II	Tübingen		Germany	72076
47	Universitätsklinikum Ulm - Klinik fur Innere Medizin III	Ulm		Germany	89081
48	Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II	Würzburg		Germany	97080
49	University of Athens - Alexandra Hospital	Athens		Greece	14572
50	Università degli Studi di Bologna - Policlinico S. Orsola - Hematology	Bologna		Italy	40138
51	AO Universitaria San Martino - hematooncology	Genova		Italy	16132
52	Fondazione "G. Pascale" - Hematology	Napoli		Italy	80131
53	Ospedale San Luigi AO Luigi Gonzaga - Hematology	Orbassano		Italy	10043
54	Universita degli Studi di Padova - Clinical & Experimental Medicine	Padova		Italy	35128
55	Ospedale Guglielmo da Saliceto - hematooncology	Piacenza		Italy	29100
56	Unità di Ematologia Arcispedale S. Maria Nuova - Haematology	Reggio Emilia		Italy	42100
57	Policlinico Umberto I, Università "La Sapienza" di Roma - Hematology	Roma		Italy	00161
58	A.O.U. San Giovanni Battista - Hematology	Torino		Italy	10126
59	VUMC - Hematology	Amsterdam		Netherlands	1081 HV
60	Erasmus Medical Center - Hematology	Rotterdam		Netherlands	3015 CE
61	University Medical Center - Hematology	Utrecht		Netherlands	3584 CX
62	Hematological Research Center under the Russian Academy of Medical Sciences - Hematology & BMT	Moscow		Russian Federation	125167
63	Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin - Hematology	Moscow		Russian Federation	125284
64	Russian Research Institute of Hematology and Blood Transfusion - Hematology	St. Petersburg		Russian Federation	191024
65	State Higher Educational Institution St. Petersburg State Medical University - Onco-hematology	St. Petersburg		Russian Federation	197341
66	Hospital Germans Trias i Pujol - Hematology	Badalona		Spain	08916
67	Hospital Clinic i Provincial de Barcelona - Hematology	Barcelona		Spain	08036
68	Hospital de Donostia - Hematology	Guipúzcoa		Spain	20014
69	Hospital de La Princesa - Hematology	Madrid		Spain	28006
70	Hospital 12 de Octubre - Hematology	Madrid		Spain	28041
71	Hospital de Salamanca - Hematology	Salamanca		Spain	37007
72	Hospital Universitario Marqués de Valdecilla - Hematology	Santander		Spain	39008
73	Hospital La Fe - Hematology	Valencia		Spain	46009
74	Sahlgrenska Hospital, University of Goteborg - Hematology	Goteborg		Sweden	S-41345
75	Karolinska University Hospital Huddinge - Center of hematology	Stockholm		Sweden	14152
76	Karolinska University Hospital-medicine	Stockholm		Sweden	14186
77	Karolinska University Hospital Solna- medicine	Stockholm		Sweden	17176
78	Overlakare Medocomcentrum - Hematology	Uppsala		Sweden	75185
79	Inselspital, Institut für Medizinische Onkologie	Bern		Switzerland	3010
80	Hôpitaux Universitaire de Genève - Oncologie	Genève		Switzerland	1211
81	Klinik und Poliklinik für Onkologie - UniversitätsSpital Zürich	Zürich		Switzerland	8091
82	Royal Bournemouth Hospital - Haematology	Bournemouth		United Kingdom	BH7 7DW
83	St James's University Hospital - Haematology	Leeds		United Kingdom	LS9 7TF
84	St Bartholomew's Hospital - Medical Oncology	London		United Kingdom	EC1A 7BE
85	King's College Hospital - Haematology Clinical Trials	London		United Kingdom	SE5 9RS
86	Freeman Hospital - Northern Centre for Cancer Care	Newcastle Upon Tyne		United Kingdom	NE7 7DN
87	Nottingham City Hospital - Centre for Clinical Haematology	Nottingham		United Kingdom	NG5 1PB
88	Derriford Hospital - Haematology	Plymouth		United Kingdom	PL6 8DH
89	Royal hallamshire Hospital - Haematology	Sheffield		United Kingdom	S10 2JF
90	Royal Marsden NHS Foundation Trust - Haematology	Surrey		United Kingdom	SM2 5PT
91	Royal Wolverhampton Hospitals Trust - Research and Development	Wolverhampton		United Kingdom	WV10 OQP

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Mohamed Zaki, MD, PhD, Celgene Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

• Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.
• Moreau P, Weisel KC, Song KW, Gibson CJ, Saunders O, Sternas LA, Hong K, Zaki MH, Dimopoulos MA. Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS). Leuk Lymphoma. 2016 Dec;57(12):2839-2847. Epub 2016 May 13.
• Morgan G, Palumbo A, Dhanasiri S, Lee D, Weisel K, Facon T, Delforge M, Oriol A, Zaki M, Yu X, Sternas L, Jacques C, Akehurst R, Offner F, Dimopoulos MA. Overall survival of relapsed and refractory multiple myeloma patients after adjusting for crossover in the MM-003 trial for pomalidomide plus low-dose dexamethasone. Br J Haematol. 2015 Mar;168(6):820-3. doi: 10.1111/bjh.13227. Epub 2014 Nov 18.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT01324947
• Other Study ID Numbers: CC-4047-MM-003/C; 2010-023343-16
• First Posted: Mar 29, 2011
• Last Update Posted: Nov 19, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Celgene: Myeloma; Multiple Myeloma; Relapsed Multiple Myeloma; Relapsed and Refractory Multiple Myeloma; Refractory Myeloma; Resistant Multiple Myeloma; Treatment-resistant Multiple Myeloma; Pomalidomide; Lenalidomide-resistant; Bortezomib-resistant; Companion
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Pomalidomide

Study Results

Participant Flow

Pre-assignment Detail	CC-4047-MM003C is a companion study for the trial CC-4047-MM-003 (NCT01311687). CC-4047-MM-003C enrolled those who discontinued treatment with dexamethasone alone (Treatment Arm B) in the CC-4047-MM-003 trial due to disease progression; those who had discontinued treatment with pomalidomide plus dexamethasone (Arm A) were not eligible to enroll

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Period Title: Overall Study
STARTED	74
Safety Population	73
Efficacy Evaluable Population (EEP)	64
COMPLETED	0
NOT COMPLETED	74

Baseline Characteristics

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Overall Participants	74
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (9.25)
Sex: Female, Male (Count of Participants)
Female	32 43.2%
Male	42 56.8%
Race (participants) [Number]
American Indian or Alaska Native	0 0%
Asian	0 0%
Black or African American	1 1.4%
Native Hawaiian or Other Pacific Islanders	0 0%
White	52 70.3%
Other	2 2.7%
Not Collected	19 25.7%
Ethnicity (participants) [Number]
Hispanic or Latino	6 8.1%
Not Hispanic or Latino	49 66.2%
Not Collected	19 25.7%
Participants with Prior Anti-Myeloma (MM) Therapies (participants) [Number]
Number [participants]	74 100%
Durie-Salmon Multiple Myeloma Stage before Study Entry (participants) [Number]
Stage I	8 10.8%
Stage II	15 20.3%
Stage III	50 67.6%
Missing	1 1.4%
Time From First Pathologic Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.6 (3.72)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment
Description	Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment. 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. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame	From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.

Outcome Measure Data

Analysis Population Description

Intent to Treat Population was defined as all enrolled participants.

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	74
Number [percentage of participants]	23.0 31.1%

2. Secondary Outcome

Title	Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment
Description	Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following: 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.
Time Frame	From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.

Outcome Measure Data

Analysis Population Description

Intent to treat population includes all participants enrolled.

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity pomalidomide: Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	74
Number [percentage of participants]	20.3 27.4%

3. Secondary Outcome

Title	Number of Participants With Adverse Events and Type of Adverse Events
Description	An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: Results in death; Is life-threatening; Requires or prolongs existing inpatient hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death
Time Frame	From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.

Outcome Measure Data

Analysis Population Description

Safety population includes all participants who received at least one dose of study drug.

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	73
Any adverse event	73 98.6%
Grade 3-4 adverse event	64 86.5%
AE related to pomalidomide	51 68.9%
Grade 3-4 AE related to pomalidomide	33 44.6%
Grade 5 AE	19 25.7%
≥1 Serious AE (SAE)	52 70.3%
≥1 SAE related to pomalidomide	15 20.3%
≥1 SAE leading to stopping pomalidomide	6 8.1%
≥AE leading to discontinuation of pomalidomide	8 10.8%
≥1 study drug related AE leading to stopping POM	1 1.4%
≥1 AE leading to reduction of pomalidomide	11 14.9%
≥1 study drug related AE leading to reducing POM	9 12.2%
≥1 AE leading to interruption of pomalidomide	41 55.4%
≥ 1 study drug related interruption of POM	25 33.8%

4. Secondary Outcome

Title	Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG
Description	Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl) Urine M-component (absolute increase ≥ 200 mg/24 hours) In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) Bone marrow plasma cell percentage (absolute % ≥ 10%) Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
Time Frame	From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.

Outcome Measure Data

Analysis Population Description

Intent to Treat included all participants enrolled.

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	74
Median (95% Confidence Interval) [weeks]	16.0

5. Secondary Outcome

Title	Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria
Description	Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl) Urine M-component (absolute increase ≥ 200 mg/24 hours) In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) Bone marrow plasma cell percentage (absolute % ≥ 10%) Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Time Frame	From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to progression follow-up was 90.3 weeks.

Outcome Measure Data

Analysis Population Description

Intent to Treat includes all participants enrolled

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	74
Median (95% Confidence Interval) [weeks]	19.0

6. Secondary Outcome

Title	Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria
Description	Duration of Response (calculated for responders only) is defined as the time from the initial documented response (partial response or better) to confirmed disease progression by the investigator based on IMWG criteria.
Time Frame	From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum duration of response follow-up was 90.3 weeks.

Outcome Measure Data

Analysis Population Description

Includes those who had a partial response or better.

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity pomalidomide: Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	17
Median (95% Confidence Interval) [weeks]	28.3

7. Secondary Outcome

Title	Kaplan-Meier Estimate for Overall Survival
Description	Overall survival was calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Time Frame	From randomization through the follow-up phase; Maximum time on follow-up was 141.1 weeks.

Outcome Measure Data

Analysis Population Description

Intent to Treat population included all participants enrolled into the study

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	74
Median (95% Confidence Interval) [weeks]	33.6

8. Secondary Outcome

Title	Time to Response Based on IMWG and Assessed by the Investigator
Description	Time to Response was calculated as the time from enrollment to the initial response (PR or better) based on IMWG and assessed by the investigator.
Time Frame	From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to response was 23.1 weeks

Outcome Measure Data

Analysis Population Description

Includes those who had at least a partial response or better; Intent to Treat

Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
Measure Participants	17
Median (Full Range) [weeks]	8.3

Adverse Events

Time Frame	From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.
Arm/Group Title	Pomalidomide
Arm/Group Description	Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity
All Cause Mortality
	Pomalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pomalidomide
	Affected / at Risk (%)	# Events
Total	52/73 (71.2%)
Blood and lymphatic system disorders
Anaemia	10/73 (13.7%)
Neutropenia	3/73 (4.1%)
Febrile neutropenia	2/73 (2.7%)
Thrombocytopenia	1/73 (1.4%)
Cardiac disorders
Atrial fibrillation	1/73 (1.4%)
Cardiac failure	1/73 (1.4%)
Cardiac failure congestive	1/73 (1.4%)
Sinus tachycardia	1/73 (1.4%)
Gastrointestinal disorders
Abdominal pain	1/73 (1.4%)
Diarrhoea	4/73 (5.5%)
Dysphagia	1/73 (1.4%)
Gastrointestinal haemorrhage	1/73 (1.4%)
Intestinal infarction	1/73 (1.4%)
Vomiting	1/73 (1.4%)
General disorders
Fatigue	2/73 (2.7%)
General physical health deterioration	8/73 (11%)
Asthenia	2/73 (2.7%)
Pyrexia	1/73 (1.4%)
Infections and infestations
Pneumonia	11/73 (15.1%)
Bronchitis	1/73 (1.4%)
Bronchopneumonia	2/73 (2.7%)
Neutropenic sepsis	2/73 (2.7%)
Sepsis	2/73 (2.7%)
Enterocolitis infectious	2/73 (2.7%)
Septic shock	2/73 (2.7%)
Cellulitis	1/73 (1.4%)
Clostridium difficile colitis	1/73 (1.4%)
Erysipelas	1/73 (1.4%)
Gastroenteritis	1/73 (1.4%)
Infection	1/73 (1.4%)
Lower respiratory tract infection	1/73 (1.4%)
Meningitis cryptococcal	1/73 (1.4%)
Otitis media	1/73 (1.4%)
Pneumonia streptococcal	1/73 (1.4%)
Respiratory tract infection	1/73 (1.4%)
Subcutaneous abscess	1/73 (1.4%)
Injury, poisoning and procedural complications
Hip fracture	1/73 (1.4%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/73 (1.4%)
Hypokalaemia	2/73 (2.7%)
Hypomagnesaemia	1/73 (1.4%)
Hypercalcaemia	4/73 (5.5%)
Decreased appetite	2/73 (2.7%)
Cachexia	1/73 (1.4%)
Dehydration	1/73 (1.4%)
Hyperglycaemic hyperosmolar nonketotic syndrome	1/73 (1.4%)
Hyperproteinaemia	1/73 (1.4%)
Musculoskeletal and connective tissue disorders
Osteolysis	2/73 (2.7%)
Back pain	1/73 (1.4%)
Musculoskeletal chest pain	1/73 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of bladder	1/73 (1.4%)
Multiple myeloma	1/73 (1.4%)
Prostate cancer	1/73 (1.4%)
Nervous system disorders
Spinal cord compression	1/73 (1.4%)
Psychiatric disorders
Confusional state	2/73 (2.7%)
Renal and urinary disorders
Renal failure acute	4/73 (5.5%)
Renal failure	3/73 (4.1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	4/73 (5.5%)
Lung disorder	2/73 (2.7%)
Dyspnoea	1/73 (1.4%)
Pleural effusion	1/73 (1.4%)
Pulmonary oedema	1/73 (1.4%)
Vascular disorders
Hypotension	1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	Pomalidomide
	Affected / at Risk (%)	# Events
Total	68/73 (93.2%)
Blood and lymphatic system disorders
Anaemia	36/73 (49.3%)
Neutropenia	35/73 (47.9%)
Thrombocytopenia	16/73 (21.9%)
Leukopenia	9/73 (12.3%)
Gastrointestinal disorders
Constipation	16/73 (21.9%)
Diarrhoea	11/73 (15.1%)
Nausea	9/73 (12.3%)
Vomiting	5/73 (6.8%)
General disorders
Fatigue	16/73 (21.9%)
Pyrexia	13/73 (17.8%)
Asthenia	7/73 (9.6%)
Oedema peripheral	6/73 (8.2%)
Infections and infestations
Bronchitis	6/73 (8.2%)
Gastroenteritis	5/73 (6.8%)
Upper respiratory tract infection	5/73 (6.8%)
Urinary tract infection	5/73 (6.8%)
Nasopharyngitis	4/73 (5.5%)
Investigations
Weight decreased	6/73 (8.2%)
Blood creatinine increased	4/73 (5.5%)
Metabolism and nutrition disorders
Hypokalaemia	13/73 (17.8%)
Hypercalcaemia	11/73 (15.1%)
Decreased appetite	7/73 (9.6%)
Musculoskeletal and connective tissue disorders
Back pain	13/73 (17.8%)
Bone pain	12/73 (16.4%)
Arthralgia	5/73 (6.8%)
Muscle spasms	5/73 (6.8%)
Nervous system disorders
Headache	7/73 (9.6%)
Psychiatric disorders
Insomnia	4/73 (5.5%)
Renal and urinary disorders
Renal failure	4/73 (5.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	15/73 (20.5%)
Cough	9/73 (12.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	6/73 (8.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Institution may publish the results of its findings if a multicenter publication is not forthcoming within 18 months after study completion. Institution shall provide Celgene with a copy of the papers prior to submission; Celgene shall complete its review within 60 days after receipt. Upon Celgene's request, proposed publication or presentation will be delayed up to 60 additional days to enable Celgene to secure adequate intellectual property protection of patentable material.