Dasatinib in Combination With Revlimid (and Dexamethasone)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00560391
First received: November 16, 2007
Last updated: November 14, 2013
Last verified: November 2013
Results First Received: June 15, 2012  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mg
Drug: Dasatinib, 70 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg
Drug: Dasatinib, 100 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg
Drug: Dasatinib, 100 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg
Drug: Dasatinib, 140 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg

  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
Of 39 participants were enrolled in this study, 4 never received treatment due to screening failure. A total of 35 participants received treatment.

Reporting Groups
  Description
Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 70 mg QD for 28 days and lenalidomide 15 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 70 mg QD for 28 days and lenalidomide 20 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 100 mg QD for 28 days and lenalidomide 20 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 100 mg QD for 28 days and lenalidomide 25 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 140 mg QD for 28 days and lenalidomide 25 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22). Cohort includes 4 participants treated for dose -finding phase and 13 participants treated in dose expansion phase.

Participant Flow:   Overall Study
    Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg     Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg     Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg     Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg     Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg  
STARTED     6 [1]   3 [1]   3 [1]   6 [1]   17 [1]
COMPLETED     6 [2]   3 [3]   3 [4]   5 [5]   15 [6]
NOT COMPLETED     0     0     0     1     2  
Still on treatment                 0                 0                 0                 1                 2  
[1] Participants who received treatment
[2] Completed=off treatment;Disease progression-1;Death-1;Max. clinical benefit-2;Study drug toxicity-2
[3] Completed=off treatment; Disease progression-1;Death-1; Unrelated AE-1
[4] Completed=off treatment; Disease progression-1;Maximum clinical benefit-1; Unrelated AE-1
[5] Completed=off treatment; Disease progression-2; Unrelated AE 1 and Subject request 2
[6] Completed=offtreatment;Disease progression-6;Study drug toxicity-7; Unrelated AE-1,Subject request-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.
No text entered.

Reporting Groups
  Description
Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 70 mg QD for 28 days and lenalidomide 15 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 70 mg QD for 28 days and lenalidomide 20 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 100 mg QD for 28 days and lenalidomide 20 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 100 mg QD for 28 days and lenalidomide 25 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22).
Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg Participants were treated with a combination of dasatinib, lenalidomide and dexamethasone in 28 day cycles (dasatinib 140 mg QD for 28 days and lenalidomide 25 mg QD for 21 days, along with 40 mg QD of dexamethasone given weekly on Days 1, 8, 15, and 22). Cohort includes 4 participants treated for dose –finding phase and 13 participants treated in dose expansion phase.
Total Total of all reporting groups

Baseline Measures
    Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg     Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg     Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg     Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg     Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg     Total  
Number of Participants  
[units: participants]
  6     3     3     6     17     35  
Age  
[units: years]
Mean ± Standard Deviation
  66.2  ± 11.75     69.3  ± 4.73     63.0  ± 11.14     69.7  ± 5.92     59.3  ± 8.06     63.4  ± 9.19  
Age, Customized  
[units: participants]
           
21 - 45 years     0     0     0     0     1     1  
46 - 65 years     3     1     2     1     13     20  
66 - 75 years     1     2     1     5     3     12  
>75 years     2     0     0     0     0     2  
Gender  
[units: participants]
           
Female     4     2     1     4     7     18  
Male     2     1     2     2     10     17  
Race/Ethnicity, Customized  
[units: participants]
           
White     6     3     3     6     16     34  
Asian     0     0     0     0     1     1  
International Staging System (ISS) [1]
[units: participants]
           
Stage I     1     0     1     0     4     6  
Stage II     1     0     0     3     2     6  
Stage III     1     2     0     1     1     5  
Not assessed     3     1     2     2     10     18  
Durie-Salmon Staging System [2]
[units: participants]
           
Stage IA     3     1     2     1     2     9  
Stage IB     0     0     0     0     0     0  
Stage IIA     0     0     1     3     3     7  
Stage IIB     0     0     0     0     0     0  
Stage IIIA     3     2     0     0     6     11  
Stage IIIB     0     0     0     0     0     0  
Not Assessed     0     0     0     2     6     8  
Time from diagnosis to first dosing  
[units: years]
Median ( Full Range )
  4.9  
  ( 2 to 18 )  
  4.0  
  ( 1 to 5 )  
  7.5  
  ( 7 to 11 )  
  5.2  
  ( 1 to 6 )  
  3.7  
  ( 1 to 16 )  
  4.4  
  ( 1 to 18 )  
[1] The ISS is an updated staging system for multiple myeloma. ISS divides multiple myeloma into three stages, which indicate the effect the disease is having on the body and how quickly or slowly it may develop. The ISS is based on the levels of blood proteins beta-2 microglobulin (β2M) and albumin. Stage I= β2M: <3.5 mg/L, albumin: >=3.5 g/dL; Stage II= β2M level: < 3.5 mg/L and albumin: < 3.5 g/dL, or β2M =3.5 to 5.5 mg/dL; Stage III: β2M level: >=5.5 mg/L.
[2] Myeloma is classified into 3 stages. Stage I: hemoglobin (Hb) >10g/dL, normal calcium levels, normal skeletal survey or single plasmacytoma or osteoporosis, serum paraprotein level<5g/dL if immunoglobulin G(IgG), <3g/dL if IgA, urinary light chain excretion<4g/24h. Stage II: fulfilling the criteria of neither I nor III. Stage III: Hb<8.5g/dL, high calcium >12mg/dL, Skeletal survey of 3 or more lytic bone lesions, serum paraprotein >7g/dL if IgG,>5g/dL if IgA, urinary light chain excretion >12g/24h. Each stage further subdivided: A= serum creatinine <2mg/dL and B= serum creatinine >2mg/dL.



  Outcome Measures
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1.  Primary:   Recommended Phase II Dose (RP2D) of the Combination (Dasatinib + Lenalidomide + Dexamethasone)   [ Time Frame: From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]

2.  Primary:   Number of Participants With Dose-limiting Toxicity (DLT)   [ Time Frame: From the date of first dose until at least 30 days after the last dose of study drug (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]

3.  Primary:   Number of Participants in the Dose Escalation Phase Who Reached Maximum Tolerated Dose (MTD) of Dasatinib With Lenalidomide and Dexamethasone   [ Time Frame: From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]

4.  Primary:   Number of Participants Who Died, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation   [ Time Frame: Baseline (pretreatment), from the date of first dose until at least 30 days after the last dose of study drug (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]

5.  Primary:   Number of Participants With Hematology Abnormalities (Worst On-study Grade vs Baseline): Leukopenia, Neutropenia, Thrombocytopenia, and Anemia   [ Time Frame: Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo]) ]

6.  Primary:   Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin (TB), and Serum Creatinine (SC)   [ Time Frame: Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo]) ]

7.  Primary:   Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): High Calcium, Low Calcium, Low Magnesium, and Low Phosphorus   [ Time Frame: Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo]) ]

8.  Secondary:   Number of Participants With Complete Response and Very Good Partial Response   [ Time Frame: Baseline, At the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]

9.  Secondary:   Number of Participants With Partial Response   [ Time Frame: Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]

10.  Secondary:   Number of Participants With Minimal Response   [ Time Frame: Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]). ]


  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: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00560391     History of Changes
Other Study ID Numbers: CA180-180
Study First Received: November 16, 2007
Results First Received: June 15, 2012
Last Updated: November 14, 2013
Health Authority: United States: Food and Drug Administration
France: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Australia: Department of Health and Ageing Therapeutic Goods Administration