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Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

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ClinicalTrials.gov Identifier: NCT00793650
Recruitment Status : Terminated
First Posted : November 19, 2008
Results First Posted : June 18, 2012
Last Update Posted : August 30, 2012
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Sagar Lonial, Emory University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cancer
Multiple Myeloma
Interventions Drug: Bortezomib
Drug: Melphalan
Procedure: Autologous PBSC Transplant
Enrollment 39
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll
Hide Arm/Group Description

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

Period Title: Overall Study
Started 19 20
Completed 19 20
Not Completed 0 0
Arm/Group Title Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll Total
Hide Arm/Group Description

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

Total of all reporting groups
Overall Number of Baseline Participants 19 20 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
14
  73.7%
14
  70.0%
28
  71.8%
>=65 years
5
  26.3%
6
  30.0%
11
  28.2%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 20 participants 39 participants
58.32  (7.92) 58.75  (8.05) 58.54  (7.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
Female
9
  47.4%
7
  35.0%
16
  41.0%
Male
10
  52.6%
13
  65.0%
23
  59.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 20 participants 39 participants
19 20 39
1.Primary Outcome
Title Safety and Engraftment
Hide Description Peripheral blood progenitor cells were collected with either chemo-mobilization (27 of 39, 69%) or growth factor mobilization (12 of 39, 31%). Patients received an average of 9.0 × 10^6/kg CD34+ cells (range, 2.3-65) as their transplant graft.
Time Frame Day 30 after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
As per the protocol
Arm/Group Title Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll
Hide Arm/Group Description:

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

Overall Number of Participants Analyzed 19 20
Median (Full Range)
Unit of Measure: days
Median time for platelet recovery
16
(8 to 23)
16
(10 to 58)
Median time for neutrophil recovery
12
(10 to 18)
12
(9 to 35)
2.Secondary Outcome
Title Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant.
Hide Description

CR :Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow.

VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 hour.

Partial Response:>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200mg per 24 hour.

Time Frame 100 days after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
As per the protocol.
Arm/Group Title Bortezomib Before Melphalan Bortezomib After Melphalan
Hide Arm/Group Description:

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

Overall Number of Participants Analyzed 19 20
Measure Type: Number
Unit of Measure: participants
Complete response (CR) 2 6
VGPR-Very good partial remission 9 11
Partial Response 6 7
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll
Hide Arm/Group Description

All patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

patients received melphalan (100 mg/m^2/day × 2; days

−3 and −2), for a total dose of 200 mg/m^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m^2

All-Cause Mortality
Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll
Affected / at Risk (%) Affected / at Risk (%)
Total   4/19 (21.05%)   2/20 (10.00%) 
General disorders     
Expired  3/19 (15.79%)  1/20 (5.00%) 
Acute pulmonary embolus  0/19 (0.00%)  1/20 (5.00%) 
Hemorrhage/Bleeding-Hemorrhage  1/19 (5.26%)  0/20 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bortezomib Before HD Melphalan Bortezomib After HD melphalanAll
Affected / at Risk (%) Affected / at Risk (%)
Total   19/19 (100.00%)   18/20 (90.00%) 
Blood and lymphatic system disorders     
Febrile Neutropenia  11/19 (57.89%)  13/20 (65.00%) 
Cardiac disorders     
Hypotension  4/19 (21.05%)  2/20 (10.00%) 
A.fib  1/19 (5.26%)  0/20 (0.00%) 
sinus bradycardia  1/19 (5.26%)  0/20 (0.00%) 
Gastrointestinal disorders     
Muscositis  18/19 (94.74%)  16/20 (80.00%) 
Diarrhea  16/19 (84.21%)  18/20 (90.00%) 
Nausea  19/19 (100.00%)  18/20 (90.00%) 
Vomiting  11/19 (57.89%)  11/20 (55.00%) 
Clostridium diificile  3/19 (15.79%)  1/20 (5.00%) 
Esophagitis  1/19 (5.26%)  0/20 (0.00%) 
Gastrointestinal bleed  1/19 (5.26%)  0/20 (0.00%) 
Neutopenic colitis  0/19 (0.00%)  1/20 (5.00%) 
General disorders     
Hypernatremia  2/19 (10.53%)  1/20 (5.00%) 
Headaches  1/19 (5.26%)  0/20 (0.00%) 
Hepatobiliary disorders     
Liver Toxicities  5/19 (26.32%)  4/20 (20.00%) 
Infections and infestations     
Sepsis  3/19 (15.79%)  2/20 (10.00%) 
Musculoskeletal and connective tissue disorders     
Bone Pain  0/19 (0.00%)  1/20 (5.00%) 
Nervous system disorders     
Cognitive disturbances  2/19 (10.53%)  1/20 (5.00%) 
Seizures  1/19 (5.26%)  0/20 (0.00%) 
Renal and urinary disorders     
Renal toxicities  4/19 (21.05%)  7/20 (35.00%) 
Incontinenece  1/19 (5.26%)  0/20 (0.00%) 
Urinary retension  0/19 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary toxicities  2/19 (10.53%)  5/20 (25.00%) 
Skin and subcutaneous tissue disorders     
Rash  2/19 (10.53%)  5/20 (25.00%) 
Blisters on Feet  1/19 (5.26%)  0/20 (0.00%) 
Vascular disorders     
DVT/PE  1/19 (5.26%)  1/20 (5.00%) 
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. Sagar Lonial
Organization: Emory University
Phone: 404-727-5572
EMail: sloni01@emory.edu
Layout table for additonal information
Responsible Party: Sagar Lonial, Emory University
ClinicalTrials.gov Identifier: NCT00793650    
Other Study ID Numbers: 080-2005
First Submitted: November 17, 2008
First Posted: November 19, 2008
Results First Submitted: March 14, 2012
Results First Posted: June 18, 2012
Last Update Posted: August 30, 2012