Trial Outcomes & Findings for A Study of Rituximab and Bevacizumab in Patients With Follicular Non-Hodgkin's Lymphoma (NCT NCT00193492)
NCT ID: NCT00193492
Last Updated: 2015-01-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
18 months
Results posted on
2015-01-05
Participant Flow
Participant milestones
| Measure |
Rituximab
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). Patients who have objective response or stable disease at week 12 reevaluation will receive 4 additional doses of rituximab (375 mg/m2) administered in months 3 (week 12), 5, 7, and 9.
Rituximab
|
Rituximab/Bevacizumab
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). During the 4-week course of rituximab, all patients will receive 2 doses of bevacizumab 10mg/kg IV, given on Days 3 and 15. The first dose will be given on Day 3, following rituximab on Day 1. If both drugs are well tolerated during the first dose, rituximab and bevacizumab should be given on the same day for the Day 15 dose and all subsequent doses.
Bevacizumab
Rituximab
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
29
|
|
Overall Study
COMPLETED
|
14
|
14
|
|
Overall Study
NOT COMPLETED
|
17
|
15
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Rituximab and Bevacizumab in Patients With Follicular Non-Hodgkin's Lymphoma
Baseline characteristics by cohort
| Measure |
Rituximab
n=31 Participants
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). Patients who have objective response or stable disease at week 12 reevaluation will receive 4 additional doses of rituximab (375 mg/m2) administered in months 3 (week 12), 5, 7, and 9.
Rituximab
|
Rituximab/Bevacizumab
n=29 Participants
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). During the 4-week course of rituximab, all patients will receive 2 doses of bevacizumab 10mg/kg IV, given on Days 3 and 15. The first dose will be given on Day 3, following rituximab on Day 1. If both drugs are well tolerated during the first dose, rituximab and bevacizumab should be given on the same day for the Day 15 dose and all subsequent doses.
Bevacizumab
Rituximab
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
68 years
n=7 Participants
|
67 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
29 participants
n=7 Participants
|
60 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPer 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.
Outcome measures
| Measure |
Rituximab
n=31 Participants
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). Patients who have objective response or stable disease at week 12 reevaluation will receive 4 additional doses of rituximab (375 mg/m2) administered in months 3 (week 12), 5, 7, and 9.
Rituximab
|
Rituximab/Bevacizumab
n=29 Participants
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). During the 4-week course of rituximab, all patients will receive 2 doses of bevacizumab 10mg/kg IV, given on Days 3 and 15. The first dose will be given on Day 3, following rituximab on Day 1. If both drugs are well tolerated during the first dose, rituximab and bevacizumab should be given on the same day for the Day 15 dose and all subsequent doses.
Bevacizumab
Rituximab
|
|---|---|---|
|
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
|
42 percentage of participants
Interval 25.0 to 61.0
|
48 percentage of participants
Interval 29.0 to 67.0
|
SECONDARY outcome
Timeframe: 18 monthsThe Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death or Disease Progression from NHL. Progression is defined using International Workshop Response Criteria for Non-Hodgkin's Lymphoma as - enlargment of liver/spleen, new sites, new or increased malignancy in lymph nodes, new or increased lymph node masses or reappearance of disease in bone marrow.
Outcome measures
| Measure |
Rituximab
n=31 Participants
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). Patients who have objective response or stable disease at week 12 reevaluation will receive 4 additional doses of rituximab (375 mg/m2) administered in months 3 (week 12), 5, 7, and 9.
Rituximab
|
Rituximab/Bevacizumab
n=29 Participants
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). During the 4-week course of rituximab, all patients will receive 2 doses of bevacizumab 10mg/kg IV, given on Days 3 and 15. The first dose will be given on Day 3, following rituximab on Day 1. If both drugs are well tolerated during the first dose, rituximab and bevacizumab should be given on the same day for the Day 15 dose and all subsequent doses.
Bevacizumab
Rituximab
|
|---|---|---|
|
Progression Free Survival (PFS)
|
10.4 months
Interval 4.4 to 15.9
|
20.7 months
Interval 13.8 to 54.4
|
Adverse Events
Rituximab
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Rituximab/Bevacizumab
Serious events: 8 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab
n=31 participants at risk
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). Patients who have objective response or stable disease at week 12 reevaluation will receive 4 additional doses of rituximab (375 mg/m2) administered in months 3 (week 12), 5, 7, and 9.
Rituximab
|
Rituximab/Bevacizumab
n=29 participants at risk
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). During the 4-week course of rituximab, all patients will receive 2 doses of bevacizumab 10mg/kg IV, given on Days 3 and 15. The first dose will be given on Day 3, following rituximab on Day 1. If both drugs are well tolerated during the first dose, rituximab and bevacizumab should be given on the same day for the Day 15 dose and all subsequent doses.
Bevacizumab
Rituximab
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
0.00%
0/31
|
3.4%
1/29
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
3.2%
1/31
|
3.4%
1/29
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
3.2%
1/31
|
0.00%
0/29
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.00%
0/31
|
3.4%
1/29
|
|
Psychiatric disorders
Psychiatric disorders - Other, dementia
|
0.00%
0/31
|
3.4%
1/29
|
|
Vascular disorders
Hematoma
|
0.00%
0/31
|
3.4%
1/29
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/31
|
3.4%
1/29
|
|
Infections and infestations
Bronchial infection
|
0.00%
0/31
|
3.4%
1/29
|
|
Gastrointestinal disorders
Rectal Perforation
|
0.00%
0/31
|
3.4%
1/29
|
Other adverse events
| Measure |
Rituximab
n=31 participants at risk
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). Patients who have objective response or stable disease at week 12 reevaluation will receive 4 additional doses of rituximab (375 mg/m2) administered in months 3 (week 12), 5, 7, and 9.
Rituximab
|
Rituximab/Bevacizumab
n=29 participants at risk
All patients will receive rituximab 375mg/m2 administered by slow IV infusion weekly for 4 consecutive weeks (days 1, 8, 15, and 22). During the 4-week course of rituximab, all patients will receive 2 doses of bevacizumab 10mg/kg IV, given on Days 3 and 15. The first dose will be given on Day 3, following rituximab on Day 1. If both drugs are well tolerated during the first dose, rituximab and bevacizumab should be given on the same day for the Day 15 dose and all subsequent doses.
Bevacizumab
Rituximab
|
|---|---|---|
|
General disorders
Fatigue
|
54.8%
17/31
|
69.0%
20/29
|
|
General disorders
Pain
|
45.2%
14/31
|
58.6%
17/29
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
32.3%
10/31
|
34.5%
10/29
|
|
Investigations
White blood cell decreased
|
19.4%
6/31
|
44.8%
13/29
|
|
Blood and lymphatic system disorders
Anemia
|
35.5%
11/31
|
24.1%
7/29
|
|
Investigations
Platelet count decreased
|
25.8%
8/31
|
27.6%
8/29
|
|
Vascular disorders
Hypertension
|
9.7%
3/31
|
41.4%
12/29
|
|
Gastrointestinal disorders
Nausea
|
19.4%
6/31
|
31.0%
9/29
|
|
Nervous system disorders
Headache
|
9.7%
3/31
|
37.9%
11/29
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.2%
1/31
|
37.9%
11/29
|
|
Renal and urinary disorders
Proteinuria
|
3.2%
1/31
|
37.9%
11/29
|
|
Immune system disorders
Allergic reaction
|
25.8%
8/31
|
6.9%
2/29
|
|
Infections and infestations
Infections and infestations - Other
|
9.7%
3/31
|
24.1%
7/29
|
|
General disorders
Edema
|
22.6%
7/31
|
6.9%
2/29
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
12.9%
4/31
|
17.2%
5/29
|
|
Investigations
Neutrophil count decreased
|
12.9%
4/31
|
17.2%
5/29
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
9.7%
3/31
|
17.2%
5/29
|
|
Gastrointestinal disorders
Diarrhea
|
3.2%
1/31
|
20.7%
6/29
|
|
Psychiatric disorders
Insomnia
|
16.1%
5/31
|
6.9%
2/29
|
|
Gastrointestinal disorders
Constipation
|
9.7%
3/31
|
10.3%
3/29
|
|
Nervous system disorders
Dizziness
|
9.7%
3/31
|
10.3%
3/29
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
19.4%
6/31
|
0.00%
0/29
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.2%
1/31
|
17.2%
5/29
|
|
Investigations
Alkaline phosphatase increased
|
6.5%
2/31
|
10.3%
3/29
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, hematocrit decreased
|
9.7%
3/31
|
6.9%
2/29
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/31
|
17.2%
5/29
|
|
General disorders
Fever
|
9.7%
3/31
|
6.9%
2/29
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, hyperchloremia
|
3.2%
1/31
|
13.8%
4/29
|
|
Psychiatric disorders
Psychiatric disorders - Other, mood alteration NOS
|
3.2%
1/31
|
13.8%
4/29
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
6.5%
2/31
|
10.3%
3/29
|
|
Gastrointestinal disorders
Abdominal pain
|
9.7%
3/31
|
3.4%
1/29
|
|
Metabolism and nutrition disorders
Anorexia
|
3.2%
1/31
|
10.3%
3/29
|
|
Psychiatric disorders
Anxiety
|
9.7%
3/31
|
3.4%
1/29
|
|
Investigations
Aspartate aminotransferase increased
|
3.2%
1/31
|
10.3%
3/29
|
|
General disorders
Chills
|
12.9%
4/31
|
0.00%
0/29
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.2%
1/31
|
10.3%
3/29
|
|
Investigations
Creatinine increased
|
3.2%
1/31
|
10.3%
3/29
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.7%
3/31
|
3.4%
1/29
|
|
General disorders
General disorders and administration site conditions - Other, hemorrhage
|
0.00%
0/31
|
13.8%
4/29
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
3.2%
1/31
|
10.3%
3/29
|
|
Metabolism and nutrition disorders
Hypernatremia
|
3.2%
1/31
|
10.3%
3/29
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
12.9%
4/31
|
0.00%
0/29
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
6.5%
2/31
|
6.9%
2/29
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.5%
2/31
|
6.9%
2/29
|
|
Investigations
Lymphocyte count decreased
|
3.2%
1/31
|
10.3%
3/29
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.5%
2/31
|
6.9%
2/29
|
|
Infections and infestations
Rhinitis infective
|
6.5%
2/31
|
6.9%
2/29
|
|
Infections and infestations
Sinusitis
|
3.2%
1/31
|
10.3%
3/29
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
2/31
|
6.9%
2/29
|
|
Investigations
Blood bilirubin increased
|
3.2%
1/31
|
6.9%
2/29
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
6.5%
2/31
|
3.4%
1/29
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.5%
2/31
|
3.4%
1/29
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
3.2%
1/31
|
6.9%
2/29
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/31
|
10.3%
3/29
|
|
Renal and urinary disorders
Urinary frequency
|
3.2%
1/31
|
6.9%
2/29
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days 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 propsed 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
- Publication restrictions are in place
Restriction type: OTHER