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Trial record 19 of 372 for:    LENALIDOMIDE AND Dexamethasone

Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01029054
Recruitment Status : Completed
First Posted : December 9, 2009
Results First Posted : November 20, 2014
Last Update Posted : January 30, 2017
Sponsor:
Collaborators:
Onyx Therapeutics, Inc.
Celgene
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Health Services Research
Condition Multiple Myeloma
Intervention Drug: carfilzomib, lenalidomide plus dexamethasone
Enrollment 53
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dose Escalation Cohort 1 Dose Escalation Cohort 2 Dose Escalation Cohort 3
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Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance) at dose level 20 mg/m^2.

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance) at dose level 27 mg/m^2.

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance) at dose level 36 mg/m^2.

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Period Title: Phase I
Started 4 13 18
Completed 4 13 18
Not Completed 0 0 0
Period Title: Phase II
Started 0 0 18 [1]
Completed 0 0 18
Not Completed 0 0 0
[1]
35 participants were enrolled in Ph I. 18 additional participants were enrolled in Ph II at the MTD.
Arm/Group Title Carfilzomib, Lenalidomide w/Dexamethasone
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Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Overall Number of Baseline Participants 53
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[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 53 participants
59
(35 to 81)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants
Female
14
  26.4%
Male
39
  73.6%
1.Primary Outcome
Title The Maximum Tolerated Dose (MTD) of Carfilzomib
Time Frame 6 Months
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Of the 53 patients enrolled, 35 were entered into the Phase I portion of the study.
Arm/Group Title Carfilzomib, Lenalidomide w/Dexamethasone
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Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: mg/m^2
36
2.Primary Outcome
Title The Percentage of Patients That Achieve a Response to Treatment
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The percentage of patients that achieve at least a sCR (Stringent Complete Response), at least a VGPR (Very Good Partial Response) and at least a PR (Partial Response) will be determined.

sCR is defined as:

  • Negative immunofixation on the serum and urine and
  • Disappearance of any soft tissue plasmacytomas and
  • < 5% plasma cells in bone marrow and
  • Normal SFLC ratio and
  • Absence of clonal cells in bone marrow

VGPR is defined as:

  • Serum and urine M-protein detectable by immunofixation but not on electrophoresis or
  • ≥ 90% reduction in serum M-component with urine M-component < 100 mg per 24 hours

PR is defined as:

  • ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours
  • If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required
Time Frame 4 Months After Treatment Start
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[Not Specified]
Arm/Group Title Carfilzomib, Lenalidomide w/Dexamethasone
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Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: percentage of patients
% of patients that achieve at least a sCR 42
% of patients that achieve at least a VGPR 81
% of patients that achieve at least a PR 98
3.Secondary Outcome
Title The Percentage of Patients Alive Without Progression
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The Progression Free Survival (PFS) rate will be determined at 12 and 24 months post treatment.

Progressive Disease (PD) is defined as an increase of greater than or equal to 25% from lowest response level in serum M-component and/ or urine M-component and/ or the difference between involved or uninvolved SFLC levels and/ or bone marrow % plasma cells. PD may also be the development of new bone lesions or soft tissue plasmacytomas or the increase in size of existing lesions. PD may also be the development of hypercalcemia.

Time Frame 12 Months and 24 Months Post Treatment
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[Not Specified]
Arm/Group Title Carfilzomib, Lenalidomide w/Dexamethasone
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Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

Overall Number of Participants Analyzed 53
Measure Type: Number
Unit of Measure: percentage of patients
Percentage of Patients Without Progression at 12 m 97
Percentage of Patients Without Progression at 24 m 92
Time Frame All Adverse Events (AEs) that occurred after the subject signed consent were documented.
Adverse Event Reporting Description A Serious Adverse Event (SAE) is defined as: death, a life-threatening experience, hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of an exposed subject, important medical events based upon appropriate medical judgment, pregnancy.
 
Arm/Group Title Carfilzomib, Lenalidomide w/Dexamethasone
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Carfilzomib will be administered as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

All-Cause Mortality
Carfilzomib, Lenalidomide w/Dexamethasone
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Carfilzomib, Lenalidomide w/Dexamethasone
Affected / at Risk (%)
Total   23/53 (43.40%) 
Blood and lymphatic system disorders   
Febrile Neutropenia  1/53 (1.89%) 
Anemia  2/53 (3.77%) 
Methemoglobinemia  1/53 (1.89%) 
Cardiac disorders   
Atrial Fibrillation  1/53 (1.89%) 
Rapid Ventricular Response  1/53 (1.89%) 
Gastrointestinal disorders   
Colitis  1/53 (1.89%) 
Constipation  1/53 (1.89%) 
Gastroenteritis  1/53 (1.89%) 
General disorders   
Fever  1/53 (1.89%) 
Infections and infestations   
Appendicitis  1/53 (1.89%) 
Clostridium Difficile  1/53 (1.89%) 
Pneumonia  4/53 (7.55%) 
Influenza  1/53 (1.89%) 
Urinary Tract Infection  3/53 (5.66%) 
Metabolism and nutrition disorders   
Hyperglycemia  2/53 (3.77%) 
Musculoskeletal and connective tissue disorders   
Compression Fracture  1/53 (1.89%) 
Nervous system disorders   
Acute Mental Status Change  1/53 (1.89%) 
Confusion  1/53 (1.89%) 
Grand Mal Seizure  1/53 (1.89%) 
Seizure  1/53 (1.89%) 
Renal and urinary disorders   
Acute Renal Failure  2/53 (3.77%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  2/53 (3.77%) 
Pulmonary Edema  1/53 (1.89%) 
Pulmonary Toxicity  1/53 (1.89%) 
Pulmonary Embolism  1/53 (1.89%) 
Vascular disorders   
Intracranial Hemorrhage  1/53 (1.89%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Carfilzomib, Lenalidomide w/Dexamethasone
Affected / at Risk (%)
Total   53/53 (100.00%) 
Blood and lymphatic system disorders   
Thrombocytopenia  36/53 (67.92%) 
Anemia  32/53 (60.38%) 
Neutropenia  16/53 (30.19%) 
Gastrointestinal disorders   
Diarrhea  14/53 (26.42%) 
Nausea  7/53 (13.21%) 
Constipation  5/53 (9.43%) 
General disorders   
Edema  25/53 (47.17%) 
Fatigue  20/53 (37.74%) 
Infections and infestations   
Infection  12/53 (22.64%) 
Investigations   
Elevated Liver Function Test  15/53 (28.30%) 
Metabolism and nutrition disorders   
Hyperglycemia  38/53 (71.70%) 
Hypophosphatemia  24/53 (45.28%) 
Musculoskeletal and connective tissue disorders   
Muscle Cramping  17/53 (32.08%) 
Nervous system disorders   
Peripheral Neuropathy  12/53 (22.64%) 
Psychiatric disorders   
Mood Alterations  5/53 (9.43%) 
Renal and urinary disorders   
Renal  5/53 (9.43%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  8/53 (15.09%) 
Pulmonary Embolism  3/53 (5.66%) 
Skin and subcutaneous tissue disorders   
Rash  15/53 (28.30%) 
Vascular disorders   
Phlebitis  12/53 (22.64%) 
Deep Vein Thrombosis  6/53 (11.32%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mark Kaminski, M.D.
Organization: University of Michigan Hospital
Phone: 734-936-5310
EMail: mkaminsk@umich.edu
Layout table for additonal information
Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT01029054     History of Changes
Other Study ID Numbers: UMCC 2009.056
HUM30396 ( Other Identifier: University of Michigan Medical IRB )
First Submitted: December 8, 2009
First Posted: December 9, 2009
Results First Submitted: November 13, 2014
Results First Posted: November 20, 2014
Last Update Posted: January 30, 2017