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Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma

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ClinicalTrials.gov Identifier: NCT01029730
Recruitment Status : Completed
First Posted : December 10, 2009
Results First Posted : December 28, 2015
Last Update Posted : August 19, 2016
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Cephalon
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma
Interventions Drug: Bendamustine
Drug: Bortezomib
Drug: Rituximab
Enrollment 55
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

Period Title: Combination Therapy
Started 55
Completed 39 [1]
Not Completed 16
[1]
Patients remained on-study until completing 6 cycles or coming off-treatment for any other reason
Period Title: Maintenance Therapy
Started 37 [1]
Completed 14
Not Completed 23
[1]
Two patients complete study treatment but declined subsequent maintenance therapy
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

Overall Number of Baseline Participants 55
Hide Baseline Analysis Population Description
All enrolled patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 55 participants
64
(30 to 89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Female
27
  49.1%
Male
28
  50.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 55 participants
55
1.Primary Outcome
Title Complete Response Rate
Hide Description Percentage of patients experiencing a complete response (CR) per RECIST. CR = disappearance of all target lesions.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All evaluable patients
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description:

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

Overall Number of Participants Analyzed 51
Measure Type: Number
Unit of Measure: percentage of evaluable participants
65
2.Secondary Outcome
Title Overall Response Rate
Hide Description The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame At 3 and 6 months during treatment, then 6 months post-treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients evaluable for response.
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description:

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

Overall Number of Participants Analyzed 51
Measure Type: Number
Unit of Measure: percentage of evaluable participants
94
3.Secondary Outcome
Title Median Progression-free Survival
Hide Description The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame at 3 and 6 months, then every 3 months post-treatment for 1 year and every 6 months thereafter until disease progression; projected 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description:

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

Overall Number of Participants Analyzed 55
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
[1]
Median PFS was not reached
4.Secondary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety.
Hide Description Toxicity grades will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Includes adverse events occurring in >1 patient
Time Frame Days 1,8, and 15 of each 28-day cycle for 6 months, then every 3 months for a year, projected 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description:

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

Overall Number of Participants Analyzed 55
Measure Type: Number
Unit of Measure: participants
Leukopenia 16
Neutropenia 16
Lymphopenia 9
Thrombocytopenia 4
Anemia 3
Peripheral Neuropathy 5
Diarrhea 4
Fatigue 4
Nausea/Vomiting 3
Cough 2
Rash 2
Syncope 2
Hypocalcemia/Hyponatremia 2
Time Frame 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bendamustine/Bortezomib/Rituximab
Hide Arm/Group Description

Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.

Bendamustine: Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Bortezomib: Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Rituximab: Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1

All-Cause Mortality
Bendamustine/Bortezomib/Rituximab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bendamustine/Bortezomib/Rituximab
Affected / at Risk (%)
Total   11/55 (20.00%) 
Cardiac disorders   
Atrial Fibrillation  1  1/55 (1.82%) 
Cardiac disorders - other, left ventricular diastolic dysfunction  1  1/55 (1.82%) 
Cardiac disorders - Other, tachycardia  1  1/55 (1.82%) 
Gastrointestinal disorders   
Gastrointestinal disorders - Other, bowel perforation  1  1/55 (1.82%) 
Pancreatitis  1  1/55 (1.82%) 
General disorders   
Fever  1  1/55 (1.82%) 
Infusion Related Reaction  1  1/55 (1.82%) 
Infections and infestations   
Hepatitis viral  1  1/55 (1.82%) 
Infections and infestations - Other, Perisigmoid abscess  1  1/55 (1.82%) 
Infections and infestations - Other, Varicella  1  1/55 (1.82%) 
Skin Infection  1  1/55 (1.82%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/55 (1.82%) 
Nervous system disorders   
Tremor  1  1/55 (1.82%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/55 (1.82%) 
Skin and subcutaneous tissue disorders   
Erythema Multiforme  1  1/55 (1.82%) 
Rash  1  2/55 (3.64%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bendamustine/Bortezomib/Rituximab
Affected / at Risk (%)
Total   54/55 (98.18%) 
Blood and lymphatic system disorders   
Anemia  1  25/55 (45.45%) 
Ear and labyrinth disorders   
Tinnitus  1  9/55 (16.36%) 
Gastrointestinal disorders   
Nausea  1  39/55 (70.91%) 
Constipation  1  29/55 (52.73%) 
Diarrhea  1  25/55 (45.45%) 
Vomiting  1  18/55 (32.73%) 
Mucositis  1  8/55 (14.55%) 
Abdominal Pain  1  7/55 (12.73%) 
Flatulence  1  5/55 (9.09%) 
Abdominal Distension  1  4/55 (7.27%) 
Gastroesophageal Reflux Disease  1  4/55 (7.27%) 
Dry Mouth  1  3/55 (5.45%) 
Dysphagia  1  3/55 (5.45%) 
Hemorrhoids  1  3/55 (5.45%) 
General disorders   
Fatigue  1  48/55 (87.27%) 
Edema  1  15/55 (27.27%) 
Fever  1  11/55 (20.00%) 
Chills  1  10/55 (18.18%) 
Pain  1  8/55 (14.55%) 
Flu Like Symptoms  1  3/55 (5.45%) 
Injection Site Reaction  1  3/55 (5.45%) 
Immune system disorders   
Allergic Reaction  1  6/55 (10.91%) 
Infections and infestations   
Infections And Infestations - Other, Herpes Zoster  1  8/55 (14.55%) 
Infections And Infestations - Other, Unspecified  1  6/55 (10.91%) 
Upper Respiratory Infection  1  4/55 (7.27%) 
Bronchial Infection  1  3/55 (5.45%) 
Infections And Infestations - Other, Oral Infection  1  3/55 (5.45%) 
Investigations   
Platelet Count Decreased  1  34/55 (61.82%) 
White Blood Cell Decreased  1  30/55 (54.55%) 
Neutrophil Count Decreased  1  25/55 (45.45%) 
Lymphocyte Count Decreased  1  12/55 (21.82%) 
Alanine Aminotransferase Increased  1  6/55 (10.91%) 
Alkaline Phosphatase Increased  1  5/55 (9.09%) 
Aspartate Aminotransferase Increased  1  5/55 (9.09%) 
Investigations - Other, Ldh Increased  1  5/55 (9.09%) 
Weight Loss  1  4/55 (7.27%) 
Investigations - Other, Creatinine Decreased  1  4/55 (7.27%) 
Investigations - Other, Blood Protein Decreased  1  4/55 (7.27%) 
Investigations - Other, Blood Bicarbonate Increased  1  3/55 (5.45%) 
Investigations - Other, Ldh Increased  1  3/55 (5.45%) 
Metabolism and nutrition disorders   
Hyperglycemia  1  21/55 (38.18%) 
Anorexia  1  14/55 (25.45%) 
Dehydration  1  7/55 (12.73%) 
Hypocalcemia  1  6/55 (10.91%) 
Hyponatremia  1  6/55 (10.91%) 
Hypoalbuminemia  1  5/55 (9.09%) 
Hypokalemia  1  3/55 (5.45%) 
Hypomagnesemia  1  3/55 (5.45%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  23/55 (41.82%) 
Myalgia  1  23/55 (41.82%) 
Back Pain  1  12/55 (21.82%) 
Pain In Extremity  1  12/55 (21.82%) 
Generalized Muscle Weakness  1  4/55 (7.27%) 
Bone Pain  1  3/55 (5.45%) 
Nervous system disorders   
Peripheral Sensory Neuropathy  1  29/55 (52.73%) 
Dizziness  1  14/55 (25.45%) 
Headache  1  10/55 (18.18%) 
Dysgeusia  1  8/55 (14.55%) 
Psychiatric disorders   
Insomnia  1  15/55 (27.27%) 
Anxiety  1  6/55 (10.91%) 
Depression  1  5/55 (9.09%) 
Renal and urinary disorders   
Urinary Frequency  1  3/55 (5.45%) 
Reproductive system and breast disorders   
Pelvic Pain  1  3/55 (5.45%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  13/55 (23.64%) 
Dyspnea  1  11/55 (20.00%) 
Allergic Rhinitis  1  6/55 (10.91%) 
Respiratory, Thoracic And Mediastinal Disorders - Other, Runny Nose  1  3/55 (5.45%) 
Sore Throat  1  3/55 (5.45%) 
Skin and subcutaneous tissue disorders   
Rash  1  18/55 (32.73%) 
Hyperhidrosis  1  9/55 (16.36%) 
Pruritus  1  9/55 (16.36%) 
Alopecia  1  4/55 (7.27%) 
Vascular disorders   
Hypertension  1  5/55 (9.09%) 
Hot Flashes  1  3/55 (5.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The sponsor can review/embargo results communications prior to public release for a period that is >60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John D Hainsworth, MD
Organization: Sarah Cannon Research Institute
Phone: 1-877-691-7274
EMail: asksarah@scresearch.net
Layout table for additonal information
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01029730     History of Changes
Other Study ID Numbers: SCRI LYM 66
First Submitted: December 8, 2009
First Posted: December 10, 2009
Results First Submitted: November 19, 2015
Results First Posted: December 28, 2015
Last Update Posted: August 19, 2016