Trial Outcomes & Findings for Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation (NCT NCT00369226)

NCT ID: NCT00369226

Last Updated: 2013-07-25

Results Overview

The MTD of bortezomib was evaluated at 3 dose levels: Dose level 1: 1.0 mg/m\^2 Dose level 2: 1.3 mg/m\^2 Dose level 3: 1.5 mg/m\^2 Cohorts of 3-5 pts were enrolled at each dose level. At any dose level, if no DLT in the first 3, 4, or 5 pts, then dose escalation would occur. If 3 evaluable pts in cohort, and 1 of 3 experiences DLT then 2 additional pts treated at the same dose level. If \>=1 of 2 additional pts experience DLT then previous dose level will be MTD. If no DLT in additional 2 pts then dose escalation will occur. If 4 evaluable pts in cohort, and 1 of the 4 experiences DLT then 1 additional pt treated at same dose level. If this additional pt experiences DLT then the previous dose will be declared to be the MTD. If additional pt does not experience DLT, then dose escalation will take place. If 5 evaluable pts in cohort, and 1 experiences DLT, then dose escalation will take place. If \>=2 of first 3, 4, or 5 pts experience DLT then the previous dose will be declared MTD.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: by day 45 post PBSC infusion
• Results posted on: 2013-07-25

Participant Flow

Participant milestones

Measure	Phase I (45 Days) Bortezomib plus tacrolimus and methotrexate after mismatched allogeneic non-myeloablative hematopoietic stem cell transplantation (HSCT).	Phase II (45 Days)
Phase I (45 Days) STARTED	13	0
Phase I (45 Days) COMPLETED	13	0
Phase I (45 Days) NOT COMPLETED	0	0
Phase II (45 Days) STARTED	0	32
Phase II (45 Days) COMPLETED	0	32
Phase II (45 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation

Baseline characteristics by cohort

Measure	Phase I n=13 Participants	Phase II n=32 Participants	Total n=45 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	25 Participants n=7 Participants	38 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	32 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: by day 45 post PBSC infusion

The MTD of bortezomib was evaluated at 3 dose levels:

Dose level 1: 1.0 mg/m^2 Dose level 2: 1.3 mg/m^2 Dose level 3: 1.5 mg/m^2 Cohorts of 3-5 pts were enrolled at each dose level. At any dose level, if no DLT in the first 3, 4, or 5 pts, then dose escalation would occur.

If 3 evaluable pts in cohort, and 1 of 3 experiences DLT then 2 additional pts treated at the same dose level. If >=1 of 2 additional pts experience DLT then previous dose level will be MTD. If no DLT in additional 2 pts then dose escalation will occur. If 4 evaluable pts in cohort, and 1 of the 4 experiences DLT then 1 additional pt treated at same dose level. If this additional pt experiences DLT then the previous dose will be declared to be the MTD. If additional pt does not experience DLT, then dose escalation will take place. If 5 evaluable pts in cohort, and 1 experiences DLT, then dose escalation will take place. If >=2 of first 3, 4, or 5 pts experience DLT then the previous dose will be declared MTD.

Outcome measures

Measure	Phase I n=13 Participants	Overall Survival (OS) This reports on all treated patients across both phase I and phase II (n=45)
The Maximally Tolerated Dose (MTD) of Bortezomib (Velcade) That Can be Administered With Tacrolimus and Methotrexate After Mismatched Allogeneic Non-myeloablative Peripheral Blood Stem Cell (PBSC) Transplantation	1.3 mg/m^2	—

PRIMARY outcome

Timeframe: by day 45 post PBSC infusion

Percentage of participants who did not experience failure to engraft or relapse or death before assessment.

Outcome measures

Measure	Phase I n=37 Participants	Overall Survival (OS) This reports on all treated patients across both phase I and phase II (n=45)
Successful Initial Engraftment by Day 45 Post Peripheral Blood Stem Cell (PBSC) Infusion and Administration of Bortezomib (Velcade), Tacrolimus and Methotrexate	97 percentage of participants	—

PRIMARY outcome

Timeframe: by day 100 after peripheral blood stem cell (PBSC) infusion

Outcome measures

Measure	Phase I n=45 Participants	Overall Survival (OS) This reports on all treated patients across both phase I and phase II (n=45)
Incidence of Grade II-IV Acute Graft Versus Host Disease (GVHD) by Day 100.	22 percentage of participants Interval 11.0 to 35.0	—

SECONDARY outcome

Timeframe: by day 100 post transplant

Population: Several subjects experienced failure to graft, relapse or death prior to assessment and were removed from analysis.

As measured by median total donor chimerism at day 100.

Outcome measures

Measure	Phase I n=35 Participants	Overall Survival (OS) This reports on all treated patients across both phase I and phase II (n=45)
Sustained Engraftment Following Transplant.	97 percentage of participants	—

SECONDARY outcome

Timeframe: by 1 year after PBSC infusion

Number of participants with chronic GVHD at 1 year post transplant.

Outcome measures

Measure	Phase I n=45 Participants	Overall Survival (OS) This reports on all treated patients across both phase I and phase II (n=45)
Incidence of Chronic Graft Versus Host Disease (Chronic GVHD).	29 percentage of participants Interval 16.0 to 43.0	—

SECONDARY outcome

Timeframe: by 1 year after PBSC infusion

Progression is defined as disease relapse or disease progression since transplant.

Outcome measures

Measure	Phase I n=45 Participants	Overall Survival (OS) n=45 Participants This reports on all treated patients across both phase I and phase II (n=45)
Overall Survival and Progression-free Survival.	60 percentage of participants Interval 44.0 to 73.0	76 percentage of participants Interval 60.0 to 86.0

Adverse Events

Phase I-II

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase I-II n=45 participants at risk
Blood and lymphatic system disorders Febrile neutropenia	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.
Infections and infestations Parainfluenzae sinusitis	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.
Injury, poisoning and procedural complications Cerebrovascular accident with parathesias	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.
Metabolism and nutrition disorders Hyperglycemia	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.
Vascular disorders Deep vein thrombosis/pulmonary embolus	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.
Infections and infestations Clostridium difficile diarrhea	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.
Infections and infestations Coagulase-negative staphylococcal bacteremia	2.2% 1/45 • Number of events 1 • By day 45 post PBSC infusion.

Other adverse events

Adverse event data not reported

Additional Information

John Koreth, MBBS, D.Phil

Dana-Farber Cancer Institute

Phone: (617) 632-2949

Email: jkoreth@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place