Trial Outcomes & Findings for Bortezomib, Rituximab and Combination Chemotherapy in Treating Participants With Mantle Cell Lymphoma (NCT NCT00477412)
NCT ID: NCT00477412
Last Updated: 2022-01-28
Results Overview
Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperCVAD in patients with untreated aggressive mantle cell lymphoma.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
107 participants
Primary outcome timeframe
Cycle 1 Day 1 - End of Cycle 2 up to 60 days.
Results posted on
2022-01-28
Participant Flow
Patients with newly diagnosed MCL were enrolled into a phase 2 trial approved by the institutional review boards of both. The University of Texas MD Anderson Cancer Center and John Theurer Cancer Center at Hackensack University.
Participant milestones
| Measure |
Phase I Bortezomib 0.7 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase I Bortezomib 1.0 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase 1 Maximum Tolerated Dose (MTD) 1.3 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase II- Treatment (Combination Chemotherapy) 1.3 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
5
|
95
|
|
Overall Study
COMPLETED
|
3
|
3
|
4
|
87
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
8
|
Reasons for withdrawal
| Measure |
Phase I Bortezomib 0.7 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase I Bortezomib 1.0 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase 1 Maximum Tolerated Dose (MTD) 1.3 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase II- Treatment (Combination Chemotherapy) 1.3 mg/m^2
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|---|---|---|
|
Overall Study
Death
|
0
|
0
|
0
|
4
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
2
|
|
Overall Study
Second Malignancy
|
0
|
0
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
0
|
Baseline Characteristics
Bortezomib, Rituximab and Combination Chemotherapy in Treating Participants With Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
Phase I Bortezomib 0.7 mg/m^2
n=4 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase I Bortezomib 1.0 mg/m^2
n=3 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase 1 Maximum Tolerated Dose (MTD) 1.3 mg/m^2
n=5 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase II- Treatment (Combination Chemotherapy)
n=95 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Total
n=107 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
40 years
n=5 Participants
|
40 years
n=7 Participants
|
40 years
n=5 Participants
|
61 years
n=4 Participants
|
51 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
67 Participants
n=4 Participants
|
79 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
67 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
66 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
95 participants
n=4 Participants
|
107 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 Day 1 - End of Cycle 2 up to 60 days.Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperCVAD in patients with untreated aggressive mantle cell lymphoma.
Outcome measures
| Measure |
Phase 1 Maximum Tolerated Dose (MTD)
n=12 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|
|
Maximum Tolerated Dose of Bortezomib (Phase I)
|
1.3 mg/m^2
|
PRIMARY outcome
Timeframe: First date of diagnosis up to 5 yearsFailure will be defined as recurrence/progression of disease or death from either disease or toxicity. Bayesian toxicity monitoring schema will be used to monitor severe toxicity profile in combined therapy. Severe toxicity is defined as at least two episodes of neutropenic fever during treatment courses.
Outcome measures
| Measure |
Phase 1 Maximum Tolerated Dose (MTD)
n=95 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|
|
Time to Failure (Phase II)
|
55 months
Interval 0.0 to 60.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: Overall Response Rate was measured in Phase II only. No data collected for Phase I.
Response rate is determined by CT scans of the chest, abdomen, and pelvis, unilateral BM biopsy and aspirate with lymphoma markers (if initially positive) and colonoscopy/endoscopy if applicable.
Outcome measures
| Measure |
Phase 1 Maximum Tolerated Dose (MTD)
n=94 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|
|
Number of Participants With Overall Response Rate
|
87 Participants
|
SECONDARY outcome
Timeframe: Date of diagnosis to last known date of survival, up to 5 yearsPopulation: Overall Response Rate was measured in Phase II only. No data collected for Phase I.
Overall survival is the time in number of months from start of study treatment to date of death due to any cause.
Outcome measures
| Measure |
Phase 1 Maximum Tolerated Dose (MTD)
n=94 Participants
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|
|
Overall Survival
|
44 months
Interval 1.0 to 60.0
|
Adverse Events
Phase I Bortezomib 0.7 mg/m^2
Serious events: 1 serious events
Other events: 4 other events
Deaths: 4 deaths
Phase I Bortezomib 1.0 mg/m^2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Phase 1 Maximum Tolerated Dose (MTD) Bortezomib 1.3 mg/m^2
Serious events: 1 serious events
Other events: 4 other events
Deaths: 5 deaths
Phase II- Treatment (Combination Chemotherapy)
Serious events: 45 serious events
Other events: 94 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Phase I Bortezomib 0.7 mg/m^2
n=4 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase I Bortezomib 1.0 mg/m^2
n=3 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase 1 Maximum Tolerated Dose (MTD) Bortezomib 1.3 mg/m^2
n=5 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase II- Treatment (Combination Chemotherapy)
n=94 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|---|---|---|
|
Infections and infestations
Neutropenic Fever
|
25.0%
1/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
47.9%
45/94 • up to 5 years
|
Other adverse events
| Measure |
Phase I Bortezomib 0.7 mg/m^2
n=4 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase I Bortezomib 1.0 mg/m^2
n=3 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase 1 Maximum Tolerated Dose (MTD) Bortezomib 1.3 mg/m^2
n=5 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
Phase II- Treatment (Combination Chemotherapy)
n=94 participants at risk
Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.
Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.
Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
|
|---|---|---|---|---|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
25.0%
1/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
25.0%
1/4 • up to 5 years
|
66.7%
2/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
100.0%
4/4 • up to 5 years
|
100.0%
3/3 • up to 5 years
|
80.0%
4/5 • up to 5 years
|
100.0%
94/94 • up to 5 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
100.0%
4/4 • up to 5 years
|
100.0%
3/3 • up to 5 years
|
80.0%
4/5 • up to 5 years
|
100.0%
94/94 • up to 5 years
|
|
Infections and infestations
Infection
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
11.7%
11/94 • up to 5 years
|
|
Infections and infestations
Cellulitis
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
4.3%
4/94 • up to 5 years
|
|
Infections and infestations
Line Infection
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
2.1%
2/94 • up to 5 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
3.2%
3/94 • up to 5 years
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
3.2%
3/94 • up to 5 years
|
|
Cardiac disorders
Atrial Fibrillation/ Flutter
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
2.1%
2/94 • up to 5 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
1/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
General disorders
Fatigue
|
25.0%
1/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Infections and infestations
Sinus Infection
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Investigations
Leukocytosis
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Investigations
Anemia
|
100.0%
4/4 • up to 5 years
|
100.0%
3/3 • up to 5 years
|
80.0%
4/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Infections and infestations
Cystitis
|
0.00%
0/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Infections and infestations
Wound Infection
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Infections and infestations
Urinary Tract Infection
|
25.0%
1/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Psychiatric disorders
Psychosis
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Blood and lymphatic system disorders
Petechiae
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
25.0%
1/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Investigations
Leukopenia
|
75.0%
3/4 • up to 5 years
|
100.0%
3/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Vascular disorders
Hypotension
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
General disorders
Fever (Non-NP)
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Investigations
Elevated ALT
|
0.00%
0/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
20.0%
1/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
Investigations
Elevated AST
|
25.0%
1/4 • up to 5 years
|
33.3%
1/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
|
General disorders
Edema (HN)
|
25.0%
1/4 • up to 5 years
|
0.00%
0/3 • up to 5 years
|
0.00%
0/5 • up to 5 years
|
0.00%
0/94 • up to 5 years
|
Additional Information
Michael Wang, Professor, Lymphoma-Myeloma
UT MD Anderson Cancer Center
Phone: (713) 792-2860
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place