MTD, Safety, and Efficacy of Pomalidomide (CC-4047) Alone or With Low-dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00833833
First received: January 30, 2009
Last updated: May 1, 2013
Last verified: May 2013
Results First Received: March 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: Pomalidomide
Drug: Dexamethasone
Drug: Aspirin

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Phase 2: Participants were stratified by age (≤ 75 vs. > 75), prior number of treatments (2 vs. > 2), and prior thalidomide exposure (yes vs. no).

Reporting Groups
  Description
Phase 1: 2 mg Pomalidomide Pomalidomide 2 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 1: 3 mg Pomalidomide Pomalidomide 3 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 1: 4 mg Pomalidomide Pomalidomide 4 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 1: 5 mg Pomalidomide Pomalidomide 5 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 2: Pomalidomide + Dexamethasone Combination therapy of 4 mg pomalidomide given once per day on Days 1-21 of each 28-day cycle and the starting dose of dexamethasone (either 40mg or 20 mg) on days 1, 8, 15, and 22 of each 28-day cycle.
Phase 2: Pomalidomide 4 mg pomalidomide was given once per day on Days 1-21 of each 28-day cycle until PD. Participants in the single agent pomalidomide treatment arm who developed confirmed PD at any time had the option to receive oral dexamethasone at the starting dose in addition to their current dose of pomalidomide, or to discontinue treatment.

Participant Flow for 2 periods

Period 1:   Phase 1 (as of 01 April 2011)
    Phase 1: 2 mg Pomalidomide     Phase 1: 3 mg Pomalidomide     Phase 1: 4 mg Pomalidomide     Phase 1: 5 mg Pomalidomide     Phase 2: Pomalidomide + Dexamethasone     Phase 2: Pomalidomide  
STARTED     6     8     14     10     0     0  
COMPLETED     2 [1]   3 [1]   5 [1]   4 [1]   0     0  
NOT COMPLETED     4     5     9     6     0     0  
Still active in study                 0                 0                 2                 2                 0                 0  
Withdrawal by Subject                 1                 1                 2                 2                 0                 0  
Adverse Event                 1                 0                 2                 1                 0                 0  
Death                 0                 1                 2                 0                 0                 0  
Disease progression - unconfirmed                 1                 0                 1                 0                 0                 0  
Unspecified                 1                 3                 0                 1                 0                 0  
[1] Confirmed progressive disease

Period 2:   Phase 2 (as of 01 April 2011)
    Phase 1: 2 mg Pomalidomide     Phase 1: 3 mg Pomalidomide     Phase 1: 4 mg Pomalidomide     Phase 1: 5 mg Pomalidomide     Phase 2: Pomalidomide + Dexamethasone     Phase 2: Pomalidomide  
STARTED     0     0     0     0     113     108  
Safety Population     0     0     0     0     112     107  
COMPLETED     0     0     0     0     58 [1]   47 [1]
NOT COMPLETED     0     0     0     0     55     61  
Still active in study                 0                 0                 0                 0                 23                 22  
Adverse Event                 0                 0                 0                 0                 8                 13  
Death                 0                 0                 0                 0                 8                 9  
Disease progression - unconfirmed                 0                 0                 0                 0                 7                 6  
Withdrawal by Subject                 0                 0                 0                 0                 5                 7  
Unspecified                 0                 0                 0                 0                 4                 3  
Lost to Follow-up                 0                 0                 0                 0                 0                 1  
[1] Confirmed progressive disease



  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 from both phases

Reporting Groups
  Description
Phase 1: 2 mg Pomalidomide Pomalidomide 2 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 1: 3 mg Pomalidomide Pomalidomide 3 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 1: 4 mg Pomalidomide Pomalidomide 4 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 1: 5 mg Pomalidomide Pomalidomide 5 mg daily on days 1-21 of each 28-day cycle. Upon PD, participants had the option of discontinuing treatment or adding dexamethasone.
Phase 2: Pomalidomide + Dexamethasone Combination therapy of 4 mg pomalidomide given once per day on Days 1-21 of each 28-day cycle and the starting dose of dexamethasone (either 40mg or 20 mg) on days 1, 8, 15, and 22 of each 28-day cycle.
Phase 2: Pomalidomide 4 mg pomalidomide was given once per day on Days 1-21 of each 28-day cycle until PD. Participants in the single agent pomalidomide treatment arm who developed confirmed PD at any time had the option to receive oral dexamethasone at the starting dose in addition to their current dose of pomalidomide, or to discontinue treatment.
Total Total of all reporting groups

Baseline Measures
    Phase 1: 2 mg Pomalidomide     Phase 1: 3 mg Pomalidomide     Phase 1: 4 mg Pomalidomide     Phase 1: 5 mg Pomalidomide     Phase 2: Pomalidomide + Dexamethasone     Phase 2: Pomalidomide     Total  
Number of Participants  
[units: participants]
  6     8     14     10     113     108     259  
Age  
[units: years]
Mean ± Standard Deviation
  64.7  ± 6.83     70.4  ± 6.63     67.5  ± 8.98     61.3  ± 14.06     64.4  ± 9.24     62.9  ± 10.35     64.1  ± 9.86  
Age, Customized  
[units: participants]
             
<=75 years     6     6     11     9     99     95     226  
>75 years     0     2     3     1     14     13     33  
Gender  
[units: participants]
             
Female     5     5     4     6     51     51     122  
Male     1     3     10     4     62     57     137  
Race/Ethnicity, Customized  
[units: participants]
             
Asian     0     0     0     2     2     3     7  
Black or African American     1     0     0     0     17     16     34  
White     5     8     14     8     92     86     213  
Other     0     0     0     0     2     3     5  
Baseline Electrocardiogram Findings  
[units: participants]
             
Normal     3     3     3     4     53     44     110  
Abnormal, not clinically significant     3     5     11     6     56     59     140  
Abnormal, clinically significant     0     0     0     0     0     1     1  
Missing     0     0     0     0     4     4     8  
Eastern Cooperative Oncology Group Performance Status [1]
[units: participants]
             
0     1     0     3     2     32     24     62  
1     1     8     10     5     68     71     163  
2     4     0     1     3     13     11     32  
3     0     0     0     0     0     2     2  
Baseline Multiple Myeloma Stage [2]
[units: participants]
             
Stage I     1     1     3     2     8     8     23  
Stage II     0     1     4     1     29     29     64  
Stage III     5     6     7     7     76     71     172  
Prior Anti-Myeloma Therapies  
[units: participants]
             
Yes     6     8     14     10     113     108     259  
No     0     0     0     0     0     0     0  
Prior Thalidomide Exposure  
[units: participants]
             
Yes     4     6     11     9     76     72     178  
No     2     2     3     1     37     36     81  
Prior Stem Cell Transplant  
[units: participants]
             
Yes     4     4     11     6     84     82     191  
No     2     4     3     4     29     26     68  
[1]

The ECOG scale is as follows:

Grade 0: Fully active, able to carry on all pre-disease activities without restriction; Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair.

[2] Multiple myeloma has three stages, which are known as stage I, stage II and stage III. Staging in myeloma is done on the basis of the value of serum albumin and beta-2 microglobulin level. Stage I has the best prognosis and stage III the worst prognosis.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase 1: Participants With Dose-Limiting Toxicities (DLT) in Cycle 1   [ Time Frame: Up to Day 28 (Cycle 1) ]

2.  Primary:   Phase 2: Kaplan-Meier Estimates of Progression-free Survival (PFS) as of the 01 April 2011 Cut-off   [ Time Frame: up to 67 weeks ]

3.  Primary:   Phase 2: Percentage of Participants With Progression-Free Survival (PFS) Events as of the 01 April 2011 Cut-off   [ Time Frame: up to 67 weeks ]

4.  Secondary:   Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Single-Agent Pomalidomide as of the 01 April 2011 Cut-off   [ Time Frame: Up to week 104 ]

5.  Secondary:   Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Pomalidomide and Dexamethasone as of the 01 April 2011 Cut-off   [ Time Frame: Up to week 126 ]

6.  Secondary:   Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as of the 01 April 2011 Cut-off   [ Time Frame: Up to week 70 ]

7.  Secondary:   Phase 2: Summary of Best Myeloma Response As Assessed by Independent Response Adjudication Committee (IRAC) Using European Group for Blood and Bone Marrow Transplant (EBMT) Criteria as of the 01 April 2011 Cut-off   [ Time Frame: up to 70 weeks ]

8.  Secondary:   Phase 2: Kaplan-Meier Estimates of Duration of Response as of the 01 April 2011 Cut-off   [ Time Frame: up to 70 weeks ]

9.  Secondary:   Phase 2: Time to Response as of the 01 April 2011 Cut-off   [ Time Frame: up to 70 weeks ]

10.  Secondary:   Phase 2: Kaplan-Meier Estimates of Overall Survival as of the 01 April 2011 Cut-off   [ Time Frame: up to 70 weeks ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Associate Director, Clinical Trials Disclosure
Organization: Celgene Corporation
phone: 1-888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com


No publications provided by Celgene Corporation

Publications automatically indexed to this study:

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00833833     History of Changes
Other Study ID Numbers: CC-4047-MM-002
Study First Received: January 30, 2009
Results First Received: March 8, 2013
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board