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Trial record 77 of 1147 for:    "Follicular lymphoma"

Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory Follicular Lymphoma

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ClinicalTrials.gov Identifier: NCT00510887
Recruitment Status : Terminated (Low accrual.)
First Posted : August 2, 2007
Results First Posted : April 21, 2014
Last Update Posted : May 12, 2014
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma, Follicular
Interventions Drug: Bortezomib
Drug: Rituximab
Drug: Fludarabine
Drug: Mitoxantrone
Drug: Dexamethasone
Enrollment 14
Recruitment Details  
Pre-assignment Details Of the 14 subjects consented, 2 were screen failures so only 12 subjects received the study drug.
Arm/Group Title VR-FND
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Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Period Title: Overall Study
Started 12
Completed 11
Not Completed 1
Reason Not Completed
Lost to Follow-up             1
Arm/Group Title VR-FND
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Bortezomib (VELCADER) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Baseline Participants 14
Hide Baseline Analysis Population Description
All patients who were consented are included in the baseline analysis population.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 14 participants
59
(39 to 72)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
<=18 years
0
   0.0%
Between 18 and 65 years
10
  71.4%
>=65 years
4
  28.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Female
4
  28.6%
Male
10
  71.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 14 participants
14
1.Primary Outcome
Title Complete and Partial Response
Hide Description
  • Complete Response: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms and normalization of biochemical abnormalities (eg. LDH) definitely assignable to follicular lymphoma.
  • Partial Response requires the following:

    • greater than or equal to 50% decrease in the SPD of the 6 largest dominant nodes of nodal masses.
    • No increase in size of other nodes, liver, or spleen.
    • Splenic and hepatic nodes must regress by at least 50% in sum of the products (SPD).
    • Bone marrow assessment in irrelevant for determination of Partial Response since it is not measurable disease; however, if positive the type of cell should be reported.
    • No new lesions.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VR-FND
Hide Arm/Group Description:

Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: percentage of participants
64
2.Secondary Outcome
Title Duration of Response
Hide Description Duration of response is measured from time of treatment to time of disease progression
Time Frame up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VR-FND
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Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Participants Analyzed 7
Mean (Full Range)
Unit of Measure: months
16.47143
(3.4 to 43)
3.Secondary Outcome
Title Percentage of Subjects Experiencing Progression Free Survival
Hide Description Progression free survival is measured from treatment to progression or death, whichever comes first. Progressive disease is measured as: 50% or greater increase from nadir in the sum of the products (SPD) of any previously identified abnormal node and the appearance of any new lesions during or at the end of treatment.
Time Frame up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VR-FND
Hide Arm/Group Description:

Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: percentage of participants
17
4.Secondary Outcome
Title Percentage of Subjects Experiencing Overall Survival
Hide Description Overall survival is from the day of enrollment to date of death from any cause.
Time Frame up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VR-FND
Hide Arm/Group Description:

Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: percentage of participants
27
5.Secondary Outcome
Title Number of Participants With a Grade 3-4 Hematologic Toxicity.
Hide Description Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).
Time Frame up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VR-FND
Hide Arm/Group Description:

Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
7
6.Secondary Outcome
Title Number of Participants With Neuropathy, Any Grade
Hide Description Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).
Time Frame up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VR-FND
Hide Arm/Group Description:

Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
6
Time Frame From first dose of study drug to 30 days after the last dose of study drug
Adverse Event Reporting Description All adverse events are reported whether or not they are considered attributable to the study treatment.
 
Arm/Group Title VR-FND
Hide Arm/Group Description

Bortezomib (VELCADE) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Bortezomib: Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle

Rituximab: Rituximab 375 mg/m2 IV on day 1

Fludarabine: Fludarabine 25 mg/m2 IV on days 1,2,3

Mitoxantrone: Mitoxantrone 10 mg/m2 IV on day 2

Dexamethasone: Dexamethasone 20 mg orally on days 1,2,3,4,5

All-Cause Mortality
VR-FND
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
VR-FND
Affected / at Risk (%) # Events
Total   0/12 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
VR-FND
Affected / at Risk (%) # Events
Total   12/12 (100.00%)    
Blood and lymphatic system disorders   
Blood / Bone Marrow - Other * 1  2/12 (16.67%)  2
Febrile neutropenia (fever of unknown origin without documented infection) * 1  1/12 (8.33%)  1
Low Hemoglobin * 1  8/12 (66.67%)  9
Ear and labyrinth disorders   
Auditory / Ear * 1  1/12 (8.33%)  1
Eye disorders   
Vision - blurred vision * 1  2/12 (16.67%)  2
Gastrointestinal disorders   
Constipation * 1  5/12 (41.67%)  9
Diarrhea * 1  4/12 (33.33%)  4
Dry mouth / salivary gland (xerostomia) * 1  1/12 (8.33%)  1
Flatulence * 1  1/12 (8.33%)  1
Heartburn / dyspepsia * 1  1/12 (8.33%)  1
Mucositis / Stomatitis (clinical exam) * 1  1/12 (8.33%)  3
Nausea * 1  8/12 (66.67%)  10
Pain - Abdomen NOS * 1  3/12 (25.00%)  3
Pain - Anus * 1  1/12 (8.33%)  1
Pain - Dental / teeth / peridontal * 1  1/12 (8.33%)  1
Vomiting * 1  5/12 (41.67%)  9
General disorders   
Constitutional Symptoms - Other * 1  2/12 (16.67%)  2
Edema: head and neck * 1  1/12 (8.33%)  1
Edema: limb * 1  5/12 (41.67%)  5
Fatigue (asthenia, lethargy, malaise) * 1  10/12 (83.33%)  17
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) * 1  2/12 (16.67%)  2
Pain - Chest / thorax NOS * 1  2/12 (16.67%)  2
Rigors / chills * 1  3/12 (25.00%)  3
Hepatobiliary disorders   
Pain - Gallbladder * 1  1/12 (8.33%)  1
Infections and infestations   
Infection - Other * 1  1/12 (8.33%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils * 1  1/12 (8.33%)  1
Infection with unknown ANC - Mucosa * 1  1/12 (8.33%)  1
Injury, poisoning and procedural complications   
Bruising (in absence of Grade 3 or 4 thrombocytopenia) * 1  1/12 (8.33%)  1
Investigations   
High Alkaline phosphatase * 1  4/12 (33.33%)  4
High AST, SGOT (serum glutamic oxaloacetic transaminase) * 1  2/12 (16.67%)  2
Bilirubin (hyperbilirubinemia) * 1  1/12 (8.33%)  1
High Creatinine * 1  3/12 (25.00%)  3
Low Leukocytes (total WBC) * 1  10/12 (83.33%)  15
Lymphopenia * 1  5/12 (41.67%)  5
Metabolic / Laboratory - Other * 1  3/12 (25.00%)  4
Low Neutrophils / granulocytes (ANC / AGC) * 1  7/12 (58.33%)  11
Low Platelets * 1  9/12 (75.00%)  10
Weight loss * 1  2/12 (16.67%)  2
Metabolism and nutrition disorders   
Albumin, serum-low (hypoalbuminemia) * 1  2/12 (16.67%)  2
Anorexia * 1  6/12 (50.00%)  10
Calcium, serum-low (hypocalcemia) * 1  5/12 (41.67%)  7
Dehydration * 1  1/12 (8.33%)  1
Glucose, serum-high (hyperglycemia) * 1  6/12 (50.00%)  9
Glucose, serum-low (hypoglycemia) * 1  1/12 (8.33%)  1
Magnesium, serum-low (hypomagnesemia) * 1  3/12 (25.00%)  3
Sodium, serum-low (hyponatremia) * 1  2/12 (16.67%)  2
Tumor lysis syndrome * 1  1/12 (8.33%)  1
Uric Acid, serum-high (hyperuricemia) * 1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders   
Joint-function * 1  2/12 (16.67%)  2
Musculoskeletal - Flank pain * 1  1/12 (8.33%)  1
Pain - Back * 1  5/12 (41.67%)  5
Pain - Bone * 1  1/12 (8.33%)  3
Pain - Extremity-limb * 1  1/12 (8.33%)  2
Pain - Joint * 1  3/12 (25.00%)  4
Nervous system disorders   
Dizziness * 1  3/12 (25.00%)  3
Neuropathy: motor * 1  1/12 (8.33%)  1
Neuropathy: sensory * 1  5/12 (41.67%)  5
Pain - Head / headache * 1  3/12 (25.00%)  3
Taste Alteration (dysgeusia) * 1  2/12 (16.67%)  2
Psychiatric disorders   
Insomnia * 1  3/12 (25.00%)  3
Mood Alteration - Agitation * 1  1/12 (8.33%)  1
Renal and urinary disorders   
Pain - Kidney * 1  1/12 (8.33%)  1
Renal / Genitourinary - Other * 1  1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders   
Cough * 1  3/12 (25.00%)  3
Dyspnea (shortness of breath) * 1  4/12 (33.33%)  4
Hiccoughs (hiccups, singultus) * 1  4/12 (33.33%)  4
Pain - Throat / pharynx / larynx * 1  3/12 (25.00%)  4
Skin and subcutaneous tissue disorders   
Dry Skin * 1  1/12 (8.33%)  1
Nail Changes * 1  2/12 (16.67%)  2
Petechiae / purpura (hemorrhage / bleeding into skin or mucosa) * 1  1/12 (8.33%)  1
Pruritus / itching * 1  3/12 (25.00%)  3
Rash / desquamation * 1  4/12 (33.33%)  6
Sweating (diaphoresis) * 1  5/12 (41.67%)  6
Vascular disorders   
Hypotension * 1  2/12 (16.67%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
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. David Rizzieri
Organization: Duke University Medical Center
Phone: 919-668-1000
EMail: rizzi003@mc.duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00510887     History of Changes
Other Study ID Numbers: Pro00008487
8785 ( Other Identifier: DUMC old IRB number )
First Submitted: August 1, 2007
First Posted: August 2, 2007
Results First Submitted: December 18, 2013
Results First Posted: April 21, 2014
Last Update Posted: May 12, 2014