Trial Outcomes & Findings for A Phase II Study of VELCADE (Bortezomib) in Combination With Bendamustine and Rituximab in Subjects With Relapsed or Refractory Follicular Lymphoma (NCT NCT00636792)
NCT ID: NCT00636792
Last Updated: 2012-01-13
Results Overview
Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
73 participants
Primary outcome timeframe
12 weeks after the last subject completes their end of treatment visit.
Results posted on
2012-01-13
Participant Flow
Participant milestones
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Overall Study
STARTED
|
73
|
|
Overall Study
COMPLETED
|
40
|
|
Overall Study
NOT COMPLETED
|
33
|
Reasons for withdrawal
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Overall Study
Adverse Event
|
16
|
|
Overall Study
Physician Decision
|
7
|
|
Overall Study
Progressive Disease
|
4
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Other
|
3
|
Baseline Characteristics
A Phase II Study of VELCADE (Bortezomib) in Combination With Bendamustine and Rituximab in Subjects With Relapsed or Refractory Follicular Lymphoma
Baseline characteristics by cohort
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
n=73 Participants
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
49 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
24 Participants
n=5 Participants
|
|
Age Continuous
|
59.8 years
STANDARD_DEVIATION 10.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
73 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after the last subject completes their end of treatment visit.Population: Response-evaluable population is defined at patients treated with 90 mg/m\^2 bendamustine, received at least one dose of any study drug, and had at least one post baseline response assessment.
Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.
Outcome measures
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
n=60 Participants
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Number of Participants With Complete Response
|
32 participants
|
SECONDARY outcome
Timeframe: 12 weeks after the last subject completes their end of treatment visitResponse is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites.
Outcome measures
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
n=60 Participants
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Number of Participants With Overall Response (Complete and Partial Response)
|
53 participants
|
Adverse Events
VELCADE, Bendamustine, Rituximab (VBR) Treatment
Serious events: 25 serious events
Other events: 72 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
n=73 participants at risk
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Infections and infestations
Pneumonia NOS
|
2.7%
2/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Bronchitis NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Pulmonary mycosis
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Herpes zoster
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Bacteraemia
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Urinary tract infection NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.1%
3/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.7%
2/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Leukopenia NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.1%
3/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea NOS
|
2.7%
2/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Diarrhoea NOS
|
4.1%
3/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Nausea
|
4.1%
3/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Vomiting NOS
|
2.7%
2/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Ileus paralytic
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Pyrexia
|
4.1%
3/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Fatigue
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Weakness
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Disease progression NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Cardiac disorders
Sinus tachycardia
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Cardiac disorders
Acute myocardial infarction
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.7%
2/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Syncope
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Peripheral neuropathy NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Renal and urinary disorders
Renal failure acute
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Skin and subcutaneous tissue disorders
Dermatitis exfoliative NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Hepatobiliary disorders
Cholecystitis acute NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness NOS
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour lysis syndrome
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Vascular disorders
Orthostatic hypotension
|
1.4%
1/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
Other adverse events
| Measure |
VELCADE, Bendamustine, Rituximab (VBR) Treatment
n=73 participants at risk
Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
45.2%
33/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Abdominal pain NOS
|
17.8%
13/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Stomatitis
|
12.3%
9/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Pharyngolaryngeal pain
|
8.2%
6/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Flatulence
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Gastrointestinal disorders
Dyspepsia
|
6.8%
5/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Rigors
|
37.0%
27/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Chest pain
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
General disorders
Oedema lower limb
|
9.6%
7/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Dizziness (excl vertigo)
|
23.3%
17/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Dysgeusia
|
6.8%
5/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Headache NOS
|
27.4%
20/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
13.7%
10/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Nervous system disorders
Hypoaesthesia
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Anaemia NOS
|
35.6%
26/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Neutropenia
|
34.2%
25/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Skin and subcutaneous tissue disorders
Pruritus NOS
|
8.2%
6/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Skin and subcutaneous tissue disorders
Rash NOS
|
8.2%
6/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
6.8%
5/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Skin and subcutaneous tissue disorders
Skin lesion NOS
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Metabolism and nutrition disorders
Anorexia
|
23.3%
17/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Metabolism and nutrition disorders
Appetite decreased NOS
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
19.2%
14/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
8.2%
6/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.7%
10/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Musculoskeletal and connective tissue disorders
Pain in limb
|
8.2%
6/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.3%
9/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.6%
7/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Upper respiratory tract infection NOS
|
8.2%
6/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Herpes simplex
|
9.6%
7/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Infections and infestations
Oral candidiasis
|
9.6%
7/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.2%
14/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic NOS
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Psychiatric disorders
Insomnia
|
21.9%
16/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Psychiatric disorders
Anxiety NEC
|
12.3%
9/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Psychiatric disorders
Depression NOS
|
11.0%
8/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Vascular disorders
Hypotension NOS
|
9.6%
7/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Vascular disorders
Phlebitis NOS
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Vascular disorders
Hypertension NOS
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Eye disorders
Vision blurred
|
6.8%
5/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Eye disorders
Eye irritation
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Renal and urinary disorders
Urinary frequency
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Renal and urinary disorders
Dysuria
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
|
Cardiac disorders
Palpitations
|
5.5%
4/73 • Start from first dose of any study drug, end at 30 days post last dose of any study drug, or start of subsequent antineoplastic therapy, whichever occurs first.
|
Additional Information
Carol Satler
Millennium Pharmaceutical Inc
Phone: (617) 551-3729
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place