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Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia (CaRD)

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ClinicalTrials.gov Identifier: NCT01470196
Recruitment Status : Completed
First Posted : November 11, 2011
Results First Posted : May 1, 2017
Last Update Posted : November 20, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Waldenstrom's Macroglobulinemia
Interventions Drug: Dexamethasone
Drug: Carfilzomib
Drug: Rituximab
Enrollment 31

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Carfilzomib, Dexamethasone, and Rituximab
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Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Period Title: Overall Study
Started 31
Completed 31
Not Completed 0
Arm/Group Title Treatment Arm
Hide Arm/Group Description

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Overall Number of Baseline Participants 31
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants
<=18 years
0
   0.0%
Between 18 and 65 years
21
  67.7%
>=65 years
10
  32.3%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 31 participants
61
(47 to 75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants
Female
12
  38.7%
Male
19
  61.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 31 participants
31
 100.0%
1.Primary Outcome
Title Overall Response Rate
Hide Description Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
Time Frame 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Overall Number of Participants Analyzed 31
Measure Type: Count of Participants
Unit of Measure: Participants
25
  80.6%
2.Primary Outcome
Title Neuropathy Incidence Rate
Hide Description Number and percentage of participants who experienced neuropathy attributable to CaRD therapy
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Overall Number of Participants Analyzed 31
Measure Type: Count of Participants
Unit of Measure: Participants
6
  19.4%
3.Primary Outcome
Title Time to Progression
Hide Description Progression-free survival is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum IgM and 500mg/dL absolute increase from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).
Time Frame 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Overall Number of Participants Analyzed 31
Median (Inter-Quartile Range)
Unit of Measure: months
58
(9 to 65)
4.Primary Outcome
Title Major Response Rate
Hide Description Major Response Rate= Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
Time Frame 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Overall Number of Participants Analyzed 31
Measure Type: Count of Participants
Unit of Measure: Participants
22
  71.0%
5.Primary Outcome
Title Very Good Partial Response and Complete Response Rate
Hide Description This is the rate of VGPR and CR in patients on CaRD therapy. Very good partial responses are >90% reduction in serum IgM from baseline. Complete response is defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.
Time Frame 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm
Hide Arm/Group Description:

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

Overall Number of Participants Analyzed 31
Measure Type: Count of Participants
Unit of Measure: Participants
12
  38.7%
Time Frame Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment Arm
Hide Arm/Group Description

Carfilzomib, dexamethasone, rituximab

Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8

Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8

Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8

All-Cause Mortality
Treatment Arm
Affected / at Risk (%)
Total   0/31 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment Arm
Affected / at Risk (%) # Events
Total   5/31 (16.13%)    
Cardiac disorders   
Atypical chest pain  1 [1]  1/31 (3.23%)  1
Cardiomyopathy  1  1/31 (3.23%)  1
Infections and infestations   
Pneumonia  1  1/31 (3.23%)  1
Injury, poisoning and procedural complications   
Postoperative thoracic procedure complication  1 [2]  1/31 (3.23%)  1
Investigations   
Grade 4 Neutrophil count decreased  1  1/31 (3.23%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Grade 2 unrelated atypical chest pain without evidence of arrhythmia, negative x-ray, normal troponin levels.
[2]
Thoracic procedure complication requiring intubation
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment Arm
Affected / at Risk (%) # Events
Total   31/31 (100.00%)    
Gastrointestinal disorders   
Oral mucositis  1  2/31 (6.45%) 
GI cramping  1  1/31 (3.23%) 
General disorders   
Infusion related reaction  1  8/31 (25.81%) 
Fatigue  1  2/31 (6.45%) 
Infections and infestations   
Skin infection  1  9/31 (29.03%) 
Investigations   
Lipase increased  1  17/31 (54.84%) 
Serum amylase increased  1  8/31 (25.81%) 
Blood bilirubin increased  1  8/31 (25.81%) 
Neutrophil count decreased  1  11/31 (35.48%) 
Creatinine increased  1  3/31 (9.68%) 
Platelet count decreased  1  1/31 (3.23%) 
Metabolism and nutrition disorders   
Hyperglycemia  1  31/31 (100.00%) 
Hyperkalemia  1  1/31 (3.23%) 
Hypokalemia  1  1/31 (3.23%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/31 (9.68%) 
Nervous system disorders   
Peripheral Sensory Neuropathy  1  6/31 (19.35%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Steven P. Treon, MD, PhD
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2681
Responsible Party: Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01470196     History of Changes
Other Study ID Numbers: 11-279
First Submitted: September 22, 2011
First Posted: November 11, 2011
Results First Submitted: March 20, 2017
Results First Posted: May 1, 2017
Last Update Posted: November 20, 2018