A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Patients With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study (NIMBUS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01311687
First received: March 8, 2011
Last updated: March 28, 2014
Last verified: March 2014
Results First Received: March 28, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: pomalidomide
Drug: dexamethasone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Results are reported up to the data cut-off date of 1 March 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in a 2:1 ratio. Treatment phase discontinuation occurred when a participant had confirmed progressive disease. Participants who did not progress but who were intolerant to treatment, or no longer wished to receive study treatment entered the progression-free survival (PFS) follow-up period until disease progression.

Reporting Groups
  Description
Pomalidomide Plus Low-Dose Dexamethasone 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.
High-Dose Dexamethasone Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.

Participant Flow for 2 periods

Period 1:   Treatment Phase
    Pomalidomide Plus Low-Dose Dexamethasone     High-Dose Dexamethasone  
STARTED     302     153  
Received Study Treatment     300     150  
COMPLETED     242 [1]   142 [1]
NOT COMPLETED     60     11  
On treatment at data cut-off                 60                 11  
[1] Completed represents participants who discontinued from study treatment

Period 2:   PFS Follow-up Phase
    Pomalidomide Plus Low-Dose Dexamethasone     High-Dose Dexamethasone  
STARTED     8     8  
COMPLETED     5     7  
NOT COMPLETED     3     1  
On PFS follow-up at data cut-off                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat population (all participants who were randomized, regardless of whether they received study treatment or not)

Reporting Groups
  Description
Pomalidomide Plus Low-Dose Dexamethasone 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.
High-Dose Dexamethasone Participants received 40 mg dexamethasone (participants > 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.
Total Total of all reporting groups

Baseline Measures
    Pomalidomide Plus Low-Dose Dexamethasone     High-Dose Dexamethasone     Total  
Number of Participants  
[units: participants]
  302     153     455  
Age  
[units: years]
Mean ± Standard Deviation
  63.6  ± 9.33     63.7  ± 9.56     63.6  ± 9.40  
Age, Customized [1]
[units: participants]
     
≤ 75 Years Old     278     141     419  
> 75 Years Old     24     12     36  
Gender  
[units: participants]
     
Female     121     66     187  
Male     181     87     268  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     27     14     41  
Not Hispanic or Latino     228     104     332  
Unknown or Not Reported     47     35     82  
Race/Ethnicity, Customized  
[units: participants]
     
Asian     4     0     4  
Black or African American     4     3     7  
White     244     113     357  
Other     2     2     4  
Not collected     48     35     83  
Participants with Prior Anti-Myeloma (MM) Therapies  
[units: participants]
  302     153     455  
Stratification Factor 2: Disease Population [2]
[units: participants]
     
Disease Population Group 1     249     125     374  
Disease Population Group 2     8     5     13  
Disease Population Group 3     45     23     68  
Stratification Factor 3: Number of Prior Anti-MM Therapies  
[units: participants]
     
2 Prior Anti-MM Therapies     17     8     25  
>2 Prior Anti-MM Therapies     285     145     430  
Time from First Pathologic Diagnosis  
[units: years]
Mean ± Standard Deviation
  6.2  ± 4.02     6.5  ± 3.63     6.3  ± 3.89  
Multiple Myeloma Stage before Study Entry [3]
[units: participants]
     
Stage I     81     36     117  
Stage II     115     56     171  
Stage III     92     53     145  
Missing     14     8     22  
[1] Stratification Factor 1
[2]

Disease Population Group 1 is defined as refractory patients who have progressed on or within 60 days of both lenalidomide and bortezomib based treatments.

Disease Population Group 2 is defined as relapsed and refractory patients who achieved at least a partial response (PR) and progressed within 6 months after stopping treatment with lenalidomide and/or bortezomib.

Disease Population Group 3 is defined as refractory/intolerant patients who developed intolerance/toxicity after a minimum of 2 cycles of bortezomib.

[3]

The International Staging System divides myeloma into 3 stages based only on the serum beta-2 microglobulin and serum albumin levels.

Stage I: Serum beta-2 microglobulin is less than 3.5 (mg/L) and the albumin level is above 3.5 (g/L);

Stage II: Neither stage I or III, meaning that either:

  • The beta-2 microglobulin level is between 3.5 and 5.5 (with any albumin level), OR
  • The albumin is below 3.5 while the beta-2 microglobulin is less than 3.5

Stage III: Serum beta-2 microglobulin is greater than 5.5.




  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS)   [ Time Frame: From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks. ]

2.  Primary:   Progression-free Survival (PFS) With a Later Cut-off Date   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks. ]

3.  Secondary:   Number of Participants With Adverse Events (AEs)   [ Time Frame: From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 01 March 2013. Maximum time on treatment was 93 weeks. ]

4.  Secondary:   Overall Survival   [ Time Frame: From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks. ]

5.  Secondary:   Overall Survival With a Later Cut-off Date   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks. ]

6.  Secondary:   Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

7.  Secondary:   Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

8.  Secondary:   Time to Progression   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

9.  Secondary:   Time to Response   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

10.  Secondary:   Duration of Response   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

11.  Secondary:   Time to the First Hemoglobin Improvement   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

12.  Secondary:   Time to Improvement in Bone Pain   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

13.  Secondary:   Time to Improvement in Renal Function   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

14.  Secondary:   Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status   [ Time Frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. ]

15.  Secondary:   Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

16.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

17.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

18.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Fatigue Domain   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

19.  Secondary:   Change From Baseline in the EORTC QLQ-C30 Pain Domain   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

20.  Secondary:   Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

21.  Secondary:   Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

22.  Secondary:   Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score   [ Time Frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 ]

23.  Secondary:   Time to First Worsening of Quality of Life (QOL) Domains   [ Time Frame: Assessed on Day 1 of the first 6 treatment cycles. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Associate Director, Clinical Trials Disclosure
Organization: Celgene Corporation
phone: 1-888-260-1599


Publications of Results:

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01311687     History of Changes
Other Study ID Numbers: CC-4047-MM-003, 2010-019820-30
Study First Received: March 8, 2011
Results First Received: March 28, 2014
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency