Trial Outcomes & Findings for Open-Label Phase 1/2 Study of VELCADE for Injection in Patients With Light-chain (AL)-Amyloidosis (NCT NCT00298766)
NCT ID: NCT00298766
Last Updated: 2012-06-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
70 participants
Primary outcome timeframe
5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts
Results posted on
2012-06-25
Participant Flow
Participant milestones
| Measure |
Single Agent VELCADE
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 Study
STARTED
|
70
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
46
|
Reasons for withdrawal
| Measure |
Single Agent VELCADE
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 Study
Adverse Event
|
18
|
|
Overall Study
Death
|
2
|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Treatment ongoing
|
4
|
|
Overall Study
Progression of amyloid markers
|
4
|
|
Overall Study
Deterioration in KPS and organ function
|
1
|
|
Overall Study
Subjects overall condition deterioration
|
4
|
|
Overall Study
Other
|
4
|
Baseline Characteristics
Open-Label Phase 1/2 Study of VELCADE for Injection in Patients With Light-chain (AL)-Amyloidosis
Baseline characteristics by cohort
| Measure |
Single Agent VELCADE
n=70 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
43 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
27 Participants
n=5 Participants
|
|
Age Continuous
|
61 years
STANDARD_DEVIATION 10.10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
8 participants
n=5 Participants
|
|
Region of Enrollment
France
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
4 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohortsPopulation: Phase 1 Safety Population includes all subjects who received at least one dose of VELCADE in phase 1 dose escalation cohorts
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.
Outcome measures
| Measure |
Single Agent VELCADE
n=31 Participants
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
|
|---|---|
|
Maximum Tolerated Dose
|
2 participants with DLT
|
PRIMARY outcome
Timeframe: from first study-related procedure to 30 days after last dose of study medicationPopulation: Safety population
Treatment emergent adverse events observed during outcome measure time frame
Outcome measures
| Measure |
Single Agent VELCADE
n=70 Participants
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
|
|---|---|
|
Subjects With Treatment Emergent Adverse Events
|
70 participants
|
PRIMARY outcome
Timeframe: from first study-related procedure to 30 days after last dose of study medicationPopulation: Safety population
Serious treatment emergent adverse events observed during outcome measure time frame
Outcome measures
| Measure |
Single Agent VELCADE
n=70 Participants
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
|
|---|---|
|
Subjects With Serious Treatment Emergent Adverse Events
|
25 participants
|
PRIMARY outcome
Timeframe: from first study-related procedure to 30 days after last dose of study medicationPopulation: Safety population
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.
Outcome measures
| Measure |
Single Agent VELCADE
n=70 Participants
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
|
|---|---|
|
Subjects Grade 3/4/5 Treatment Emergent Adverse Events
|
43 participants
|
PRIMARY outcome
Timeframe: from first study-related procedure to 30 days after last dose of study medicationPopulation: Safety population
Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination
Outcome measures
| Measure |
Single Agent VELCADE
n=70 Participants
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
|
|---|---|
|
Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination
|
23 participants
|
SECONDARY outcome
Timeframe: from first dose of study medication to end of study visitPopulation: 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).
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.
Outcome measures
| Measure |
Single Agent VELCADE
n=49 Participants
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
|
|---|---|
|
Best Confirmed Hematologic Responders
|
33 participants responded
|
Adverse Events
Single Agent VELCADE
Serious events: 25 serious events
Other events: 70 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Single Agent VELCADE
n=70 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Cardiac disorders
Atrial fibrillation
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Cardiac disorders
Cardiac failure acute
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Cardiac disorders
Cardiac failure cogestive
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Cardiac disorders
Restrictive cardiomyopathy
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Abdominal pain
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Constipation
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Diarrhoea
|
2.9%
2/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Ileus
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Ileus paralytic
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Nausea
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Volvulus
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
2/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Fatigue
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Bacteraemia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Escherichia bacteraemia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Herpes zoster
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Lobar pneumonia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Pneumonia
|
4.3%
3/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Respiratory tract infection
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Staphylococcal bacteraemia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Upper respiratory tract infection
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Injury, poisoning and procedural complications
Fall
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Injury, poisoning and procedural complications
Hip fracture
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Metabolism and nutrition disorders
Fluid retention
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Autonomic neuropathy
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Cerebral ischaemia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Loss of consciousness
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Neuralgia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Psychiatric disorders
Insomnia
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Renal and urinary disorders
Renal failure
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Renal and urinary disorders
Renal failure acute
|
2.9%
2/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Renal and urinary disorders
Penal impairment
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Rash generalized
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Vascular disorders
Hypotension
|
2.9%
2/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Vascular disorders
Orthostatic hypotension
|
1.4%
1/70 • from first study-related procedure to 30 days after last dose of study medication
|
Other adverse events
| Measure |
Single Agent VELCADE
n=70 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
15.7%
11/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Cardiac disorders
Palpitations
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Eye disorders
Conjunctival haemorrhage
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Eye disorders
Conjunctivitis
|
8.6%
6/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Eye disorders
Dry eye
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Eye disorders
Vision blurred
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Abdominal distension
|
17.1%
12/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Dry mouth
|
11.4%
8/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Gastrointestinal disorders
Dyspepsia
|
8.6%
6/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Asthenia
|
12.9%
9/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Chest pain
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Chills
|
10.0%
7/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Early satiety
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Influenza like illness
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Oedema
|
21.4%
15/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Oedema peripheral
|
22.9%
16/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Pain
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
General disorders
Pyrexia
|
17.1%
12/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Bronchitis
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Cystitis
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Nasopharyngitis
|
15.7%
11/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Infections and infestations
Urinary tract infection
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Injury, poisoning and procedural complications
Contusion
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Injury, poisoning and procedural complications
Periorbital haematoma
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Metabolism and nutrition disorders
Anorexia
|
17.1%
12/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Metabolism and nutrition disorders
Dehydration
|
11.4%
8/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.4%
8/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.1%
12/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.6%
13/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
15.7%
11/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
27.1%
19/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Dizziness
|
30.0%
21/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Headache
|
22.9%
16/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
7/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Neuropathy peripheral
|
10.0%
7/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Paraesthesia
|
24.3%
17/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
14.3%
10/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Nervous system disorders
Somnolence
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Psychiatric disorders
Anxiety
|
10.0%
7/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.1%
19/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
11.4%
8/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.9%
9/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.1%
5/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.9%
9/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Vascular disorders
Hypertension
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
|
Vascular disorders
Phlebitis
|
5.7%
4/70 • from first study-related procedure to 30 days after last dose of study medication
|
Additional Information
Dr. Helgi van de Velde
Johnson & Johnson Pharmaceutical Research & Development
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place