Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 42 of 107 for:    "Vascular Hemostatic Disease" | "Doxorubicin"

Phase II Study of Velcade, Decadron, and Doxil Followed by Cyclophosphamide in Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00148317
Recruitment Status : Completed
First Posted : September 7, 2005
Results First Posted : July 18, 2017
Last Update Posted : July 18, 2017
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Bortezomib
Drug: dexamethasone
Drug: liposomal doxorubicin
Drug: cyclophoshamide
Drug: filgrastim
Enrollment 38
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Overall Study
Hide Arm/Group Description [Not Specified]
Period Title: Consolidation (VEL + DEX)
Started 38
DOXIL Added at Cycle 3 16
DOXIL Added at Cycle 5 12
no DOXIL Added 10
Completed 38
Not Completed 0
Period Title: Mobilization (VEL+CYTOXAN+FILGRASTIM)
Started 38
Completed 27
Not Completed 11
Reason Not Completed
Adverse Event             8
Lack of Efficacy             2
unable to tolerate             1
Arm/Group Title Treatment Arm (All Patients)
Hide Arm/Group Description Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin, Cyclophosphamide: Bortezomib 1.3 mg/m2 days 1, 4, 8, 11 (initial cycles) Dexamethasone 40 mg Days 1-4, 8-11, 15-18 (initial cycles) Doxil 30 mg/m2 Day 4 of subsequent cycles
Overall Number of Baseline Participants 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 38 participants
61
(27 to 76)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Age <70 years
34
  89.5%
Age > or = 70
4
  10.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Female
17
  44.7%
Male
21
  55.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
Hispanic or Latino
4
  10.5%
Not Hispanic or Latino
34
  89.5%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
   7.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  10.5%
White
26
  68.4%
More than one race
0
   0.0%
Unknown or Not Reported
5
  13.2%
Beta-2 Microglubilin  
Median (Full Range)
Unit of measure:  mg/L
Number Analyzed 38 participants
2.05
(1.0 to 10.2)
Serum Albumin  
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 38 participants
3.5
(2.0 to 4.3)
Durie Salmon Staging System   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants
1a 1
2a 19
3a 17
3b 1
[1]
Measure Description: The Durie Salmon Staging System was used to assess patients status. Stage 1A is associated with a better outcome & a low tumor burden, stage 2A with a intermediate outcome and tumor burden, and stage 3A with a worse outcome & higher tumor burden. Criteria for staging is based on multiple factors including hematology values, disease burden, and renal function. The staging system can be found here: https://www.themmrf.org/multiple-myeloma/prognosis/myeloma-stages/durie-salmon-staging-system/ As assessed by the treating physician, the 1a subject:had active myeloma based on the IMWG criteria.
International Staging System   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants
I 18
II 17
III 3
[1]
Measure Description: Measure Description: Stage I ß2-M < 3.5 mg/dL and albumin =3.5 g/dL Stage II Neither stage I nor stage III Stage III ß2-M ≥ 5.5 mg/L
Abnormalities by FISH   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants
trisomy 11 10
hyperdiploidy 7
t (4;14) 4
p53 4
del (17p) 1
t (11;14) 5
t (14;16) 2
none 16
[1]
Measure Description: Cytogenetic abnormalities were assessed in patients using fluorescence in situ hybridization (FISH), which detects chromosomal abnormalities. Del (17p), t(4;14), and t (14;16) were considered High Risk cytogenetic abnormalities. All other abnormalities were considered standard risk cytogenetics.
Prior induction therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants
lenalidomide + dexamethasone ± BIAXIN 21
Thalidomide + lenalidomide + dexamethasone± BIAXIN 8
Thalidomide + dexamethasone 3
thalidomide only 2
pulsed dexamethasone only 2
melphalan + cyclophosphamide 1
dexamethasone, then single-agent lenalidomide 1
Best response prior to induction therapy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants
Complete Response 1
partial Response 27
Stable Disease 10
[1]
Measure Description: Best response was noted using the International Myeloma Working Group Guidelines: http://imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/
1.Primary Outcome
Title Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate)
Hide Description Myeloma response criteria developed by Bladé et al. was used to categorize response.
Time Frame Best response at any point during each respective study phase was collected - once after consolidation/prior to mobilization (approximately 6 cycles after start of treatment), and once after mobilization
Hide Outcome Measure Data
Hide Analysis Population Description
All 38 patients were treated with DoVeD consolidation therapy (Vel + DEX with or without DOXIL). Of the 38 patients enrolled, 27 proceeded to mobilization (11 did not undergo mobilization). Responses were assessed prior to mobilization (post DoVED), and again after mobilization, to see if mobilization improved patient response.
Arm/Group Title Treatment Arm - Post Mobilization Treatment Arm - Responses Prior to Mobilization
Hide Arm/Group Description:
This is the response rate assessed for patients after their bortezomib-based mobilization.
This is the overall best response rate (ORR, ≥PR, as measured by ≥50% reduction in M-protein) to DoVeD therapy from post-primary induction (pre-DoVeD).
Overall Number of Participants Analyzed 27 38
Measure Type: Number
Unit of Measure: participants
Stringent Complete Response (sCR) 4 0
Complete Response (CR) 3 1
Very Good Partial response (VGPR) 6 1
Partial Response (PR) 13 2
Other Response (progression, stable disease, etc) 1 6
2.Secondary Outcome
Title Yield of CD34+ Stem Cells
Hide Description This is the yield of CD34+ stem cells collection after high dose cyclophosphamide.
Time Frame Occurred after mobilization, and prior to Stem cell transplant; a 7 day limit was imposed on stem cell collection
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm - Post Bortezomib-based Mobilization
Hide Arm/Group Description:
Yield of stem cell collection for the group that underwent bortezomib-based Mobilization
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: 10^6 cells/kg
23.2
(6.8 to 294.2)
3.Secondary Outcome
Title Progression Free Survival
Hide Description

Response was assessed using IMWG guidelines, which for progressive disease are as follows:

Increase of > 25% from lowest response value in any one or more of the following:

  • Serum M-component and/or (the absolute increase must be > 0.5 g/dL)*
  • Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
  • Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL
  • Bone marrow plasma cell percentage; the absolute percentage must be > 10%
  • Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
  • Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder IF starting M protein component is > 5g/dL, then absolute increase of 1g is sufficient for progression.
Time Frame Date of progression, assessed from start of trial to Final data cut off date (15 April 2011)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Arm (All Patients)
Hide Arm/Group Description:
Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin, Cyclophosphamide: Bortezomib 1.3 mg/m2 days 1, 4, 8, 11 (initial cycles) Dexamethasone 40 mg Days 1-4, 8-11, 15-18 (initial cycles) Doxil 30 mg/m2 Day 4 of subsequent cycles
Overall Number of Participants Analyzed 38
Median (Full Range)
Unit of Measure: months
46.6
(6.4 to 68.8)
Time Frame Safety was monitored throughout the study, from start of study until when patients were removed (for either progression, toxicity, or to get a HD-SCT, which occurred up to 1 year after start of treatment).
Adverse Event Reporting Description Safety was monitored throughout the study and adverse events (AEs) were graded by NCI-CTCAE version 3.0.
 
Arm/Group Title Treatment Arm (All Patients)
Hide Arm/Group Description Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin, Cyclophosphamide: Bortezomib 1.3 mg/m2 days 1, 4, 8, 11 (initial cycles) Dexamethasone 40 mg Days 1-4, 8-11, 15-18 (initial cycles) Doxil 30 mg/m2 Day 4 of subsequent cycles
All-Cause Mortality
Treatment Arm (All Patients)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment Arm (All Patients)
Affected / at Risk (%)
Total   1/38 (2.63%) 
Gastrointestinal disorders   
diarrhea   1/38 (2.63%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment Arm (All Patients)
Affected / at Risk (%)
Total   38/38 (100.00%) 
Blood and lymphatic system disorders   
thrombocytopenia  [1]  6/38 (15.79%) 
afebrile neutropenia  [1]  2/38 (5.26%) 
anemia  [1]  5/38 (13.16%) 
Cardiac disorders   
chest pain  [1]  2/38 (5.26%) 
hypertension  [1]  3/38 (7.89%) 
Ear and labyrinth disorders   
hearing impariment  [1]  2/38 (5.26%) 
sore throat  [1]  2/38 (5.26%) 
Eye disorders   
blurred vision  [1]  13/38 (34.21%) 
Gastrointestinal disorders   
diarrhea  [2]  2/38 (5.26%) 
nausea  [2]  6/38 (15.79%) 
diarrhea  [1]  9/38 (23.68%) 
abdominal pain  [1]  6/38 (15.79%) 
dyspepsia  [1]  5/38 (13.16%) 
constipation  [1]  15/38 (39.47%) 
nausea  [1]  5/38 (13.16%) 
increased appetite  [1]  2/38 (5.26%) 
bloating  [1]  3/38 (7.89%) 
General disorders   
dizziness  [1]  4/38 (10.53%) 
epistaxis  [1]  3/38 (7.89%) 
weight gain  [1]  3/38 (7.89%) 
fatigue  [1]  24/38 (63.16%) 
dry mouth  [1]  2/38 (5.26%) 
fever  [1]  3/38 (7.89%) 
headache  [1]  6/38 (15.79%) 
taste alteration  [1]  5/38 (13.16%) 
cough  [2]  3/38 (7.89%) 
fatigue  [2]  7/38 (18.42%) 
headache  [2]  2/38 (5.26%) 
Infections and infestations   
fever  [2]  3/38 (7.89%) 
Metabolism and nutrition disorders   
anorexia  [1]  2/38 (5.26%) 
Musculoskeletal and connective tissue disorders   
myopathy  [1]  5/38 (13.16%) 
pain in extremity  [1]  4/38 (10.53%) 
muscle weakness  [1]  7/38 (18.42%) 
cramping  [1]  2/38 (5.26%) 
back pain  [1]  7/38 (18.42%) 
Nervous system disorders   
peripheral neuropathy (sensory)  [2]  6/38 (15.79%) 
tremor  [2]  2/38 (5.26%) 
peripheral neuropathy (sensory)  [1]  28/38 (73.68%) 
hand and foot syndrome  [1]  7/38 (18.42%) 
tremor  [1]  10/38 (26.32%) 
Psychiatric disorders   
insomnia  [1]  22/38 (57.89%) 
depression  [1]  6/38 (15.79%) 
anxiety  [1]  5/38 (13.16%) 
irritability  [1]  3/38 (7.89%) 
nervousness  [1]  3/38 (7.89%) 
confusion  [1]  3/38 (7.89%) 
insomnia  [2]  2/38 (5.26%) 
anxiety  [2]  3/38 (7.89%) 
Respiratory, thoracic and mediastinal disorders   
pneumonia  [1]  2/38 (5.26%) 
cough  [1]  12/38 (31.58%) 
sinusitis  [1]  2/38 (5.26%) 
shortness of breath  [1]  4/38 (10.53%) 
nasal congestion  [1]  6/38 (15.79%) 
shortness of breath  [2]  2/38 (5.26%) 
Skin and subcutaneous tissue disorders   
dry skin  [1]  3/38 (7.89%) 
Vascular disorders   
edema  [1]  13/38 (34.21%) 
edema  [2]  2/38 (5.26%) 
Indicates events were collected by systematic assessment
[1]
DOVED consolidation phase
[2]
mobilization phase
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.
Results Point of Contact
Name/Title: Jennifer Hess
Organization: Weill Cornell Medical College
Phone: 6469629440
Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00148317     History of Changes
Other Study ID Numbers: 0504007841
First Submitted: September 2, 2005
First Posted: September 7, 2005
Results First Submitted: February 24, 2017
Results First Posted: July 18, 2017
Last Update Posted: July 18, 2017