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Trial record 1 of 1 for:    21562045 [PUBMED-IDS]
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Open-Label Phase 1/2 Study of VELCADE for Injection in Patients With Light-chain (AL)-Amyloidosis

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ClinicalTrials.gov Identifier: NCT00298766
Recruitment Status : Completed
First Posted : March 3, 2006
Results First Posted : August 13, 2010
Last Update Posted : June 25, 2012
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Amyloidosis
Intervention Drug: VELCADE
Enrollment 70

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Period Title: Overall Study
Started 70
Completed 24
Not Completed 46
Reason Not Completed
Adverse Event             18
Death             2
Withdrawal by Subject             9
Treatment ongoing             4
Progression of amyloid markers             4
Deterioration in KPS and organ function             1
Subjects overall condition deterioration             4
Other             4
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Baseline Participants 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants
<=18 years
0
   0.0%
Between 18 and 65 years
43
  61.4%
>=65 years
27
  38.6%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 70 participants
61  (10.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants
Female
31
  44.3%
Male
39
  55.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 70 participants
United States 35
Canada 8
France 3
Germany 11
Italy 9
Spain 4
1.Primary Outcome
Title Maximum Tolerated Dose
Hide Description

Maximum Tolerated Dose (MTD) was defined as the highest dose level that has 0/1 out of 6 patients experiences Dose Limited Toxicity (DLT). MTD is defined separately for QW and BIQ dose cohorts.

DLT was defined as adverse events occurring during Cycle 1 and: (1) related to VELCADE, (2) Grade 4 thrombocytopenia or neutropenia, (3) Grade 3 or higher nonhematologic toxicity.

Time Frame 5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts
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Hide Analysis Population Description
Phase 1 Safety Population includes all subjects who received at least one dose of VELCADE in phase 1 dose escalation cohorts
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description:
Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: participants with DLT
2
2.Primary Outcome
Title Subjects With Treatment Emergent Adverse Events
Hide Description Treatment emergent adverse events observed during outcome measure time frame
Time Frame from first study-related procedure to 30 days after last dose of study medication
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Hide Analysis Population Description
Safety population
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description:
Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: participants
70
3.Primary Outcome
Title Subjects With Serious Treatment Emergent Adverse Events
Hide Description Serious treatment emergent adverse events observed during outcome measure time frame
Time Frame from first study-related procedure to 30 days after last dose of study medication
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description:
Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: participants
25
4.Primary Outcome
Title Subjects Grade 3/4/5 Treatment Emergent Adverse Events
Hide Description

Grade 3/4/5 treatment emergent adverse events observed during outcome measure time frame.

Grade is determined according to Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0.

Time Frame from first study-related procedure to 30 days after last dose of study medication
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Hide Analysis Population Description
Safety population
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description:
Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: participants
43
5.Primary Outcome
Title Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination
Hide Description Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination
Time Frame from first study-related procedure to 30 days after last dose of study medication
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Hide Analysis Population Description
Safety population
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description:
Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: participants
23
6.Secondary Outcome
Title Best Confirmed Hematologic Responders
Hide Description Hematologic response was determined by the investigator per the response criteria for immunoglobulin light chain amyloidosis by Gertz (2005). It include Complete and Partial Responders (CR+PR). CR requires serum and urine negative for a monoclonal protein by immunofixation and free light chain ratio normal. PR requires: 1. reduction in quantitative serum M-protein by 50% if baseline value is at least 0.5 g/dL, 2. if light chain is detected in the urine (with a consistent peak and >100 mg/ 24 hours), then 50% reduction is required, 3. if free light chain >10 mg/dL, reduction by 50% is required.
Time Frame from first dose of study medication to end of study visit
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Hide Analysis Population Description
Efficacy population included all treated subjects with an evaluable post baseline resposne assessment in the MTD cohorts (1.6 mg/m^2 QW and 1.3 mg/m^2 BIW).
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description:
Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
Overall Number of Participants Analyzed 49
Measure Type: Number
Unit of Measure: participants responded
33
Time Frame from first study-related procedure to 30 days after last dose of study medication
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Single Agent VELCADE
Hide Arm/Group Description Bortezomib 0.7, 1.0, 1.3 and 1.6 mg/m^2 once weekly (QW) 4 doses in a 5 week cycle, and 0.7, 1.0, 1.3 mg/m^2 twice weekly (BIW) 4 doses in a 3 week cycle
All-Cause Mortality
Single Agent VELCADE
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Single Agent VELCADE
Affected / at Risk (%)
Total   25/70 (35.71%) 
Blood and lymphatic system disorders   
Thrombocytopenia  1  1/70 (1.43%) 
Cardiac disorders   
Atrial fibrillation  1  1/70 (1.43%) 
Cardiac failure acute  1  1/70 (1.43%) 
Cardiac failure cogestive  1  1/70 (1.43%) 
Restrictive cardiomyopathy  1  1/70 (1.43%) 
Gastrointestinal disorders   
Abdominal pain  1  1/70 (1.43%) 
Constipation  1  1/70 (1.43%) 
Diarrhoea  1  2/70 (2.86%) 
Ileus  1  1/70 (1.43%) 
Ileus paralytic  1  1/70 (1.43%) 
Nausea  1  1/70 (1.43%) 
Rectal haemorrhage  1  1/70 (1.43%) 
Volvulus  1  1/70 (1.43%) 
Vomiting  1  2/70 (2.86%) 
General disorders   
Fatigue  1  1/70 (1.43%) 
Infections and infestations   
Bacteraemia  1  1/70 (1.43%) 
Escherichia bacteraemia  1  1/70 (1.43%) 
Herpes zoster  1  1/70 (1.43%) 
Lobar pneumonia  1  1/70 (1.43%) 
Pneumonia  1  3/70 (4.29%) 
Respiratory tract infection  1  1/70 (1.43%) 
Staphylococcal bacteraemia  1  1/70 (1.43%) 
Upper respiratory tract infection  1  1/70 (1.43%) 
Injury, poisoning and procedural complications   
Fall  1  1/70 (1.43%) 
Hip fracture  1  1/70 (1.43%) 
Metabolism and nutrition disorders   
Fluid retention  1  1/70 (1.43%) 
Nervous system disorders   
Autonomic neuropathy  1  1/70 (1.43%) 
Cerebral ischaemia  1  1/70 (1.43%) 
Loss of consciousness  1  1/70 (1.43%) 
Neuralgia  1  1/70 (1.43%) 
Psychiatric disorders   
Insomnia  1  1/70 (1.43%) 
Renal and urinary disorders   
Renal failure  1  1/70 (1.43%) 
Renal failure acute  1  2/70 (2.86%) 
Penal impairment  1  1/70 (1.43%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/70 (1.43%) 
Interstitial lung disease  1  1/70 (1.43%) 
Pleural effusion  1  1/70 (1.43%) 
Skin and subcutaneous tissue disorders   
Hyperhidrosis  1  1/70 (1.43%) 
Rash  1  1/70 (1.43%) 
Rash generalized  1  1/70 (1.43%) 
Vascular disorders   
Hypotension  1  2/70 (2.86%) 
Orthostatic hypotension  1  1/70 (1.43%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Single Agent VELCADE
Affected / at Risk (%)
Total   70/70 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  11/70 (15.71%) 
Leukopenia  1  4/70 (5.71%) 
Cardiac disorders   
Palpitations  1  5/70 (7.14%) 
Eye disorders   
Conjunctival haemorrhage  1  5/70 (7.14%) 
Conjunctivitis  1  6/70 (8.57%) 
Dry eye  1  4/70 (5.71%) 
Vision blurred  1  5/70 (7.14%) 
Gastrointestinal disorders   
Abdominal discomfort  1  4/70 (5.71%) 
Abdominal distension  1  12/70 (17.14%) 
Abdominal pain upper  1  5/70 (7.14%) 
Dry mouth  1  8/70 (11.43%) 
Dyspepsia  1  6/70 (8.57%) 
General disorders   
Asthenia  1  9/70 (12.86%) 
Chest pain  1  4/70 (5.71%) 
Chills  1  7/70 (10.00%) 
Early satiety  1  4/70 (5.71%) 
Influenza like illness  1  5/70 (7.14%) 
Oedema  1  15/70 (21.43%) 
Oedema peripheral  1  16/70 (22.86%) 
Pain  1  4/70 (5.71%) 
Pyrexia  1  12/70 (17.14%) 
Infections and infestations   
Bronchitis  1  4/70 (5.71%) 
Cystitis  1  4/70 (5.71%) 
Nasopharyngitis  1  11/70 (15.71%) 
Urinary tract infection  1  4/70 (5.71%) 
Injury, poisoning and procedural complications   
Contusion  1  5/70 (7.14%) 
Periorbital haematoma  1  4/70 (5.71%) 
Metabolism and nutrition disorders   
Anorexia  1  12/70 (17.14%) 
Decreased appetite  1  4/70 (5.71%) 
Dehydration  1  8/70 (11.43%) 
Hypokalaemia  1  8/70 (11.43%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  12/70 (17.14%) 
Back pain  1  13/70 (18.57%) 
Muscle spasms  1  11/70 (15.71%) 
Muscular weakness  1  5/70 (7.14%) 
Musculoskeletal pain  1  4/70 (5.71%) 
Myalgia  1  4/70 (5.71%) 
Pain in extremity  1  19/70 (27.14%) 
Nervous system disorders   
Dizziness  1  21/70 (30.00%) 
Headache  1  16/70 (22.86%) 
Hypoaesthesia  1  7/70 (10.00%) 
Neuropathy peripheral  1  7/70 (10.00%) 
Paraesthesia  1  17/70 (24.29%) 
Peripheral sensory neuropathy  1  10/70 (14.29%) 
Somnolence  1  5/70 (7.14%) 
Psychiatric disorders   
Anxiety  1  7/70 (10.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  19/70 (27.14%) 
Dysphonia  1  4/70 (5.71%) 
Dyspnoea exertional  1  8/70 (11.43%) 
Oropharyngeal pain  1  9/70 (12.86%) 
Rhinorrhoea  1  4/70 (5.71%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  5/70 (7.14%) 
Ecchymosis  1  4/70 (5.71%) 
Erythema  1  5/70 (7.14%) 
Night sweats  1  4/70 (5.71%) 
Pruritus  1  9/70 (12.86%) 
Vascular disorders   
Hypertension  1  4/70 (5.71%) 
Phlebitis  1  4/70 (5.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
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: Dr. Helgi van de Velde
Organization: Johnson & Johnson Pharmaceutical Research & Development
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00298766     History of Changes
Other Study ID Numbers: 26866138-CAN-2007
First Submitted: March 1, 2006
First Posted: March 3, 2006
Results First Submitted: July 16, 2010
Results First Posted: August 13, 2010
Last Update Posted: June 25, 2012