Trial Outcomes & Findings for VELCADE®-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin's Lymphoma, or Mantle Cell Lymphoma (NCT NCT00571493)
NCT ID: NCT00571493
Last Updated: 2023-09-28
Results Overview
The maximum tolerated dose (MTD) is defined to be the dose cohort below which 3 of 6 patients experience dose limiting toxicity (DLT), or the highest dose cohort of 1.5 mg/m², if 2 DLT were not observed at any dose cohort.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
42 participants
Primary outcome timeframe
14 months
Results posted on
2023-09-28
Participant Flow
Subjects were screened and enrolled at an academic medical center in the United States.
Participant milestones
| Measure |
Phase 1: Bortezomib-0.8 mg/m²
Bortezomib dose - 0.8 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT).
|
Phase 1: Bortezomib-1.0 mg/m²
Bortezomib dose - 1.0 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT).
|
Phase 1: Bortezomib-1.3 mg/m²
Bortezomib dose - 1.3 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT).
|
Phase 1: Bortezomib-1.5 mg/m²
Bortezomib dose - 1.5 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT).
|
Phase II: Bortezomib-1.5 mg/m²
Obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with maximum tolerated dose regimen.
|
Phase II: Bortezomib-1.3 mg/m²
Obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with maximum tolerated dose regimen.
|
Phase II:Bortezomib-1.0 mg/m²
Obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with maximum tolerated dose regimen.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
3
|
3
|
11
|
12
|
6
|
|
Overall Study
COMPLETED
|
3
|
4
|
3
|
3
|
11
|
12
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
VELCADE®-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin's Lymphoma, or Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
Phase I/II
n=42 Participants
In Phase 1 of the study, bortezomib was administered in 4 dose cohorts: 0.8 mg/m², 1.0 mg/m², 1.3 mg/m² and 1.5 mg/m². Bortezomib was given on days -11, -8, -5, and -2. All study patients received BEAM conditioning: carmustine (BCNU) 300 mg/m² on day -5, etoposide 100 mg/m² twice daily on days -5, -4, -3, and -2, cytarabine 100 mg/m² twice daily on days -5, -4, -3, and -2, and melphalan 140 mg/m² on day -1 before infusion of autologous stem cells. The objective of phase 1 was to determine the maximum tolerated dose (MTD) of bortezomib in this setting. The MTD was defined by observing any nonhematologic transplantation-related toxicity higher than grade 2 on the Bearman scale occurring between day -11 and engraftment. After the MTD was defined, patients were enrolled in Phase II to obtain a preliminary estimate of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) using this regimen.
|
|---|---|
|
Age, Continuous
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
42 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 14 monthsPopulation: The MTD in Phase I was initially determined to be 1.5 mg/m2 but was later decreased to 1 mg/m2.
The maximum tolerated dose (MTD) is defined to be the dose cohort below which 3 of 6 patients experience dose limiting toxicity (DLT), or the highest dose cohort of 1.5 mg/m², if 2 DLT were not observed at any dose cohort.
Outcome measures
| Measure |
Phase I
n=13 Participants
Maximum Tolerated Dose (MTD) of Bortezomib
|
Phase II
n=29 Participants
Maximum Tolerated Dose (MTD) of Bortezomib
|
|---|---|---|
|
Maximum Tolerated Dose (MTD) of Bortezomib
|
1.5 mg/m²
|
1.0 mg/m²
|
SECONDARY outcome
Timeframe: 100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCTPopulation: One hundred days after autologous hematopoietic stem cell transplantation (ASCT), 40 participants were evaluable for response. At year one post ASCT, 38 participants were evaluable for response. Participants evaluable for the secondary endpoints (Phase II) are those who complete the transplant procedure.
To obtain a preliminary estimate of overall response rate (ORR). The overall response rate is calculated as the number of patients who achieved complete response (CR) and partial response (PR) divided by the total number of evaluable patients.
Outcome measures
| Measure |
Phase I
n=40 Participants
Maximum Tolerated Dose (MTD) of Bortezomib
|
Phase II
Maximum Tolerated Dose (MTD) of Bortezomib
|
|---|---|---|
|
Preliminary Estimate of Overall Response Rate (ORR)
Overall Response Rate (100 days after transplant)
|
38 participants
|
—
|
|
Preliminary Estimate of Overall Response Rate (ORR)
Overall Response Rate (1 year after transplant)
|
33 participants
|
—
|
SECONDARY outcome
Timeframe: one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCTPopulation: There were 38 evaluable patients at one year post autologous hematopoietic stem cell transplantation (ASCT).
To obtain a preliminary estimate of PFS and OS. Overall survival (OS) is defined as time from the first chemotherapy administered on the transplant trial until death from any cause. Progression free survival (PFS)is defined as time from therapy until relapse, progression, or death from any cause.
Outcome measures
| Measure |
Phase I
n=38 Participants
Maximum Tolerated Dose (MTD) of Bortezomib
|
Phase II
Maximum Tolerated Dose (MTD) of Bortezomib
|
|---|---|---|
|
Progression-free Survival (PFS), and Overall Survival (OS)
Progression Free Survival 1 year after transplant
|
83 percentage of participants
Interval 68.0 to 92.0
|
—
|
|
Progression-free Survival (PFS), and Overall Survival (OS)
Overall Survival 1 year after transplant
|
91 percentage of participants
Interval 79.0 to 96.0
|
—
|
|
Progression-free Survival (PFS), and Overall Survival (OS)
Progression Free Survival 5 years after transplant
|
32 percentage of participants
Interval 15.0 to 51.0
|
—
|
|
Progression-free Survival (PFS), and Overall Survival (OS)
Overall Survival 5 years after transplant
|
67 percentage of participants
Interval 50.0 to 79.0
|
—
|
Adverse Events
Phase I: Intervention
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Phase II: Survival
Serious events: 1 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I: Intervention
n=13 participants at risk
In Phase I of the study, bortezomib will be administered in 4 dose cohorts: .8 mg/m2 , 1.0 mg/m2, 1.3 mg/m2, and1.5 mg/m2. Three patients will be accrued in each dose cohort with enrollment starting at dose cohort 1 (.8 mg/m2). Bortezomib will be given on days -11,-8, -5, and -2. All study patients will receive BEAM conditioning per our standard institution protocol: carmustine (BCNU) 300 mg/m2 on day -5,etoposide 100 mg/m2 twice daily on days -5, -4, -3, and -2, cyatabine100 mg/m2 twice daily on days -5, -4, -3, and -2, and melphalan 140 mg/m2 on day -1 before infusion of autologous stem cells. The objective of phase I is to determine the maximum tolerated dose (MTD) of bortezomib in this setting. After the MTD is defined, another 20 patients will be enrolled in the Phase II portion of this protocol to obtain a preliminary estimate of the response rate.
|
Phase II: Survival
n=29 participants at risk
Patients enrolled to obtain a preliminary estimate of ORR, Progression-free survival, and overall survival (OS) using this regimen.
|
|---|---|---|
|
Gastrointestinal disorders
adynamic ileus
|
0.00%
0/13 • 3 years
|
3.4%
1/29 • Number of events 2 • 3 years
|
Other adverse events
| Measure |
Phase I: Intervention
n=13 participants at risk
In Phase I of the study, bortezomib will be administered in 4 dose cohorts: .8 mg/m2 , 1.0 mg/m2, 1.3 mg/m2, and1.5 mg/m2. Three patients will be accrued in each dose cohort with enrollment starting at dose cohort 1 (.8 mg/m2). Bortezomib will be given on days -11,-8, -5, and -2. All study patients will receive BEAM conditioning per our standard institution protocol: carmustine (BCNU) 300 mg/m2 on day -5,etoposide 100 mg/m2 twice daily on days -5, -4, -3, and -2, cyatabine100 mg/m2 twice daily on days -5, -4, -3, and -2, and melphalan 140 mg/m2 on day -1 before infusion of autologous stem cells. The objective of phase I is to determine the maximum tolerated dose (MTD) of bortezomib in this setting. After the MTD is defined, another 20 patients will be enrolled in the Phase II portion of this protocol to obtain a preliminary estimate of the response rate.
|
Phase II: Survival
n=29 participants at risk
Patients enrolled to obtain a preliminary estimate of ORR, Progression-free survival, and overall survival (OS) using this regimen.
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenic Fever
|
76.9%
10/13 • Number of events 11 • 3 years
|
65.5%
19/29 • Number of events 20 • 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/13 • 3 years
|
31.0%
9/29 • Number of events 10 • 3 years
|
|
Nervous system disorders
Peripheral Neuropathy
|
0.00%
0/13 • 3 years
|
20.7%
6/29 • Number of events 6 • 3 years
|
|
Nervous system disorders
Vasovagal syncope/orthostatic hypotension
|
7.7%
1/13 • Number of events 2 • 3 years
|
24.1%
7/29 • Number of events 8 • 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/13 • 3 years
|
17.2%
5/29 • Number of events 5 • 3 years
|
|
Gastrointestinal disorders
Ileus
|
15.4%
2/13 • Number of events 2 • 3 years
|
10.3%
3/29 • Number of events 3 • 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place