Trial Outcomes & Findings for Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors (NCT NCT01323920)

Results Overview

The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Day 100

Results posted on

2017-05-30

Participant Flow

Participant milestones

Participant milestones
Measure	Velcade/Tac/MTX Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
Overall Study STARTED	35
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Velcade/Tac/MTX Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
Overall Study Death	5
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Velcade/Tac/MTX n=34 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Region of Enrollment United States	34 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 100

Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.

The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.

Outcome measures

Outcome measures
Measure	Velcade/Tac/MTX n=34 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion	32 Percentage of participants

SECONDARY outcome

Timeframe: Day 30

Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.

To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) \>/= 500 cells/u/L

Outcome measures

Outcome measures
Measure	Velcade/Tac/MTX n=34 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion	94 Percentage of participants

SECONDARY outcome

Timeframe: 1 year

Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.

Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.

Outcome measures

Outcome measures
Measure	Velcade/Tac/MTX n=34 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion non-relapse mortality	8.8 Percent of participants
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion progression-free survival	85 Percent of participants
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion overall survival	84 Percent of participants

SECONDARY outcome

Timeframe: 1 year

Population: One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.

Outcome measures

Outcome measures
Measure	Velcade/Tac/MTX n=34 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion	53 Percentage of participants

Adverse Events

Velcade/Tac/MTX

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Velcade/Tac/MTX n=34 participants at risk Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib 1.3 mg/m\^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m\^2 IV
Immune system disorders GVHD	5.9% 2/34 • Number of events 2 • All adverse events experienced by participants will be collected from the time of the first dose of study treatment, through the study and until the final study visit. Participants continuing to experience toxicity at the off study visit may be contacted for additional assessments until the toxicity has resolved or is deemed irreversible.Participants will be followed for 1 year after transplantation or until death, whichever occurs first. AEs grade 3-5 \& SAEs whether reported by the participant, discovered during questioning, directly observed, or detected by physical examination, laboratory test or other means, will be recorded in the participant's medical record and on the appropriate study-specific case report forms. Participants removed from study treatment for unacceptable AEs will be followed until resolution or stabilization of the AE. One participant was enrolled but immediately taken off study for alternative therapy.
Infections and infestations HHV6/high LFTs	2.9% 1/34 • Number of events 1 • All adverse events experienced by participants will be collected from the time of the first dose of study treatment, through the study and until the final study visit. Participants continuing to experience toxicity at the off study visit may be contacted for additional assessments until the toxicity has resolved or is deemed irreversible.Participants will be followed for 1 year after transplantation or until death, whichever occurs first. AEs grade 3-5 \& SAEs whether reported by the participant, discovered during questioning, directly observed, or detected by physical examination, laboratory test or other means, will be recorded in the participant's medical record and on the appropriate study-specific case report forms. Participants removed from study treatment for unacceptable AEs will be followed until resolution or stabilization of the AE. One participant was enrolled but immediately taken off study for alternative therapy.
Infections and infestations Sepsis	5.9% 2/34 • Number of events 2 • All adverse events experienced by participants will be collected from the time of the first dose of study treatment, through the study and until the final study visit. Participants continuing to experience toxicity at the off study visit may be contacted for additional assessments until the toxicity has resolved or is deemed irreversible.Participants will be followed for 1 year after transplantation or until death, whichever occurs first. AEs grade 3-5 \& SAEs whether reported by the participant, discovered during questioning, directly observed, or detected by physical examination, laboratory test or other means, will be recorded in the participant's medical record and on the appropriate study-specific case report forms. Participants removed from study treatment for unacceptable AEs will be followed until resolution or stabilization of the AE. One participant was enrolled but immediately taken off study for alternative therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Relapse	2.9% 1/34 • Number of events 1 • All adverse events experienced by participants will be collected from the time of the first dose of study treatment, through the study and until the final study visit. Participants continuing to experience toxicity at the off study visit may be contacted for additional assessments until the toxicity has resolved or is deemed irreversible.Participants will be followed for 1 year after transplantation or until death, whichever occurs first. AEs grade 3-5 \& SAEs whether reported by the participant, discovered during questioning, directly observed, or detected by physical examination, laboratory test or other means, will be recorded in the participant's medical record and on the appropriate study-specific case report forms. Participants removed from study treatment for unacceptable AEs will be followed until resolution or stabilization of the AE. One participant was enrolled but immediately taken off study for alternative therapy.

Other adverse events

Adverse event data not reported

Additional Information

Dr. John Koreth

Dana Farber Cancer Institute

Phone: 617-632-2949

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place