Trial Outcomes & Findings for A Phase I/II Trial of VR-CHOP in Lymphoma Patients (NCT NCT00634179)
NCT ID: NCT00634179
Last Updated: 2016-10-27
Results Overview
INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
37 participants
Primary outcome timeframe
Cycle 1 for MTD, following completion of therapy for CR, up to 24 weeks
Results posted on
2016-10-27
Participant Flow
All patients were recruited from Winship Cancer Institute of Emory University.
A total of 37 patients were enrolled. However, not all patients participated in both phases of this study. For phase I, 19 patients were enrolled, and for phase II, 30 patients were enrolled.
Participant milestones
| Measure |
Treatment (VR-CHOP Regimen)
Phase I will identify the maximal tolerated doses of bortezomib and vincristine when used in a combination of bortezomib, rituximab and the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen.
In Phase II, the trial will evaluate the efficacy and safety of the MTD combination of VELCADE and rituximab-CHOP in additional subjects who have untreated follicular B-cell non-Hodgkin's lymphoma (B-NHL)(Grade 1, 2, 3a), small lymphocytic lymphoma, or marginal zone lymphoma.
|
|---|---|
|
Phase I: Induction
STARTED
|
19
|
|
Phase I: Induction
COMPLETED
|
19
|
|
Phase I: Induction
NOT COMPLETED
|
0
|
|
Phase II: Maintenance
STARTED
|
30
|
|
Phase II: Maintenance
COMPLETED
|
29
|
|
Phase II: Maintenance
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Treatment (VR-CHOP Regimen)
Phase I will identify the maximal tolerated doses of bortezomib and vincristine when used in a combination of bortezomib, rituximab and the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen.
In Phase II, the trial will evaluate the efficacy and safety of the MTD combination of VELCADE and rituximab-CHOP in additional subjects who have untreated follicular B-cell non-Hodgkin's lymphoma (B-NHL)(Grade 1, 2, 3a), small lymphocytic lymphoma, or marginal zone lymphoma.
|
|---|---|
|
Phase II: Maintenance
Diagnosis changed after re-review
|
1
|
Baseline Characteristics
A Phase I/II Trial of VR-CHOP in Lymphoma Patients
Baseline characteristics by cohort
| Measure |
Treatment (VR-CHOP Regimen)
n=37 Participants
INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
MAINTENANCE: Patients achieving complete response (CR) receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or partial response (PR) receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 for MTD, following completion of therapy for CR, up to 24 weeksINDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
Outcome measures
| Measure |
MTD of Bortezomib With Vincristine Capped at 1.5 mg
n=19 Participants
Maximal tolerated dose (MTD) of bortezomib when vincristine is capped at 1.5 mg
|
Phase II: Maintenance
INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
MAINTENANCE: Patients achieving CR receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or PR receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
Bortezomib: Bortezomib 1.6 mg/m² given on days 1 and 8
Rituximab: Rituximab 375 mg/m²
Doxorubicin: Doxorubicin 50 mg/m²
Cyclophosphamide: Cyclophosphamide 750 mg/m²
Vincristine: Vincristine 1.4 mg/m² (capped at 1.5 mg maximum) given on day 1
Prednisone: Prednisone 100 mg/day given orally on
|
|---|---|---|
|
Maximal Tolerated Doses of Bortezomib and Vincristine When Used in Combination of Bortezomib, Rituximab and the CHOP Chemotherapy Regimen (Phase I)
|
1.62 mg/m^2
Interval 0.63 to 1.88
|
—
|
SECONDARY outcome
Timeframe: Following completion of therapy, up to 2 yearsResponse was assessed by computerized tomography (CT) after every 2 cycles of induction therapy, one time at least 4 weeks after completing induction (i.e., prior to maintenance), and then every 3 months while on maintenance therapy. At the conclusion of maintenance therapy, patients underwent one post-treatment scan, with further scans completed at the discretion of the treating physician. Positron emission tomography was permitted but only CT measurements were used to determine response.
Outcome measures
| Measure |
MTD of Bortezomib With Vincristine Capped at 1.5 mg
n=19 Participants
Maximal tolerated dose (MTD) of bortezomib when vincristine is capped at 1.5 mg
|
Phase II: Maintenance
n=29 Participants
INDUCTION: Patients receive bortezomib IV on days 1 and 8; rituximab IV, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 60 minutes, and vincristine sulfate IV over 10 minutes on day 1; and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression.
MAINTENANCE: Patients achieving CR receive rituximab IV once every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or PR receive rituximab IV and bortezomib once weekly for 4 weeks every 6 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
Bortezomib: Bortezomib 1.6 mg/m² given on days 1 and 8
Rituximab: Rituximab 375 mg/m²
Doxorubicin: Doxorubicin 50 mg/m²
Cyclophosphamide: Cyclophosphamide 750 mg/m²
Vincristine: Vincristine 1.4 mg/m² (capped at 1.5 mg maximum) given on day 1
Prednisone: Prednisone 100 mg/day given orally on
|
|---|---|---|
|
An Estimate of the Overall Response Rate (ORR)(Complete Response [CR] + CR Unconfirmed [CRu] + Partial Response [PR]) to Bortezomib and Rituximab (VR)-CHOP According to International Workshop to Standardize Response Criteria (IWRC) Criteria
Complete Response (CR)
|
13 participants
|
19 participants
|
|
An Estimate of the Overall Response Rate (ORR)(Complete Response [CR] + CR Unconfirmed [CRu] + Partial Response [PR]) to Bortezomib and Rituximab (VR)-CHOP According to International Workshop to Standardize Response Criteria (IWRC) Criteria
Partial Response (PR)
|
6 participants
|
10 participants
|
|
An Estimate of the Overall Response Rate (ORR)(Complete Response [CR] + CR Unconfirmed [CRu] + Partial Response [PR]) to Bortezomib and Rituximab (VR)-CHOP According to International Workshop to Standardize Response Criteria (IWRC) Criteria
Overall Response Rate (ORR)
|
19 participants
|
29 participants
|
Adverse Events
Phase I: Induction
Serious events: 3 serious events
Other events: 16 other events
Deaths: 0 deaths
Phase II: Maintenance
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I: Induction
n=19 participants at risk
Phase I will identify the maximal tolerated doses of bortezomib and vincristine when used in a combination of bortezomib, rituximab and the CHOP chemotherapy regimen.
|
Phase II: Maintenance
n=29 participants at risk
In Phase II, the trial will evaluate the efficacy and safety of the MTD combination of VELCADE and rituximab-CHOP in additional subjects who have untreated follicular B-NHL. (Grade 1, 2, 3a), small lymphocytic lymphoma, or marginal zone lymphoma.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombosis
|
5.3%
1/19
|
0.00%
0/29
|
|
General disorders
Fatigue
|
0.00%
0/19
|
3.4%
1/29
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/19
|
3.4%
1/29
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/19
|
3.4%
1/29
|
|
Nervous system disorders
Pain
|
0.00%
0/19
|
3.4%
1/29
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
5.3%
1/19
|
0.00%
0/29
|
|
Psychiatric disorders
Anxiety/Depression
|
0.00%
0/19
|
3.4%
1/29
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
0.00%
0/19
|
3.4%
1/29
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/19
|
3.4%
1/29
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/19
|
3.4%
1/29
|
|
Blood and lymphatic system disorders
Extravasation
|
5.3%
1/19
|
0.00%
0/29
|
|
Cardiac disorders
Prolonged QT Interval
|
0.00%
0/19
|
3.4%
1/29
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/19
|
3.4%
1/29
|
Other adverse events
| Measure |
Phase I: Induction
n=19 participants at risk
Phase I will identify the maximal tolerated doses of bortezomib and vincristine when used in a combination of bortezomib, rituximab and the CHOP chemotherapy regimen.
|
Phase II: Maintenance
n=29 participants at risk
In Phase II, the trial will evaluate the efficacy and safety of the MTD combination of VELCADE and rituximab-CHOP in additional subjects who have untreated follicular B-NHL. (Grade 1, 2, 3a), small lymphocytic lymphoma, or marginal zone lymphoma.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
21.1%
4/19
|
10.3%
3/29
|
|
General disorders
Nausea
|
68.4%
13/19
|
6.9%
2/29
|
|
Nervous system disorders
Neuropathy
|
84.2%
16/19
|
75.9%
22/29
|
|
General disorders
Fatigue
|
57.9%
11/19
|
3.4%
1/29
|
|
Gastrointestinal disorders
Vomiting
|
47.4%
9/19
|
6.9%
2/29
|
|
Gastrointestinal disorders
Diarrhea
|
36.8%
7/19
|
3.4%
1/29
|
|
Skin and subcutaneous tissue disorders
Rash
|
21.1%
4/19
|
0.00%
0/29
|
|
Gastrointestinal disorders
Dyspepsia
|
21.1%
4/19
|
0.00%
0/29
|
|
Metabolism and nutrition disorders
Low Potassium
|
21.1%
4/19
|
6.9%
2/29
|
|
Nervous system disorders
Pain
|
63.2%
12/19
|
3.4%
1/29
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/19
|
3.4%
1/29
|
|
Blood and lymphatic system disorders
Neutropenia
|
68.4%
13/19
|
48.3%
14/29
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
0.00%
0/19
|
3.4%
1/29
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/19
|
6.9%
2/29
|
|
Blood and lymphatic system disorders
Extravasation
|
0.00%
0/19
|
3.4%
1/29
|
|
Immune system disorders
Fever
|
0.00%
0/19
|
3.4%
1/29
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/19
|
3.4%
1/29
|
|
Immune system disorders
Parotitis
|
0.00%
0/19
|
3.4%
1/29
|
|
General disorders
Weakness
|
0.00%
0/19
|
3.4%
1/29
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/19
|
3.4%
1/29
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place