Trial Outcomes & Findings for Standard of Care vs. Bortezomib in Graft-Versus Host Disease After Hematopoietic Stem Cell Transplant (NCT NCT01754389)

Last Updated: 2017-07-18

Results Overview

The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 180 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

138 participants

Primary outcome timeframe

6 months

Results posted on

2017-07-18

Participant Flow

Excluded (n= 4) * Not meeting inclusion criteria (n=3;active infection (2\*), disease relapse (2\*)) * Declined to participate (n=1; interacting medication per provider preference (1))

Participant milestones

Participant milestones
Measure	Arm A (Standard of Care) Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Overall Study STARTED	46	45	47
Overall Study COMPLETED	46	45	47
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Standard of Care vs. Bortezomib in Graft-Versus Host Disease After Hematopoietic Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Standard of Care) n=46 Participants Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant Bortezomib	Arm C (Experimental) n=47 Participants Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Sirolimus	Total n=138 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	22 Participants n=7 Participants	29 Participants n=5 Participants	70 Participants n=4 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants	23 Participants n=7 Participants	18 Participants n=5 Participants	68 Participants n=4 Participants
Age, Continuous	65 years n=5 Participants	65 years n=7 Participants	62 years n=5 Participants	64 years n=4 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants	54 Participants n=4 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	32 Participants n=7 Participants	24 Participants n=5 Participants	84 Participants n=4 Participants
Region of Enrollment United States	46 participants n=5 Participants	45 participants n=7 Participants	47 participants n=5 Participants	138 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Arm A (Standard of Care) n=46 Participants Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) n=47 Participants Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Percentage of Participants With Incidence of Grade II-IV GVHD	33 Percentage of participants Interval 20.0 to 47.0	31 Percentage of participants Interval 18.0 to 45.0	21 Percentage of participants Interval 11.0 to 34.0

SECONDARY outcome

Timeframe: 1 year

Non-relapse mortality by 1 year after stem cell infusion.

Outcome measures

Outcome measures
Measure	Arm A (Standard of Care) n=46 Participants Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) n=47 Participants Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Percentage of Participants With Non-relapse Mortality	11 Percentage of participants Interval 4.0 to 23.0	15 Percentage of participants Interval 6.0 to 28.0	6.5 Percentage of participants Interval 1.7 to 16.0

SECONDARY outcome

Timeframe: 1 year

Relapse relapse-cum-immunosuppression-free survival at 1 year after stem cell infusion

Outcome measures

Outcome measures
Measure	Arm A (Standard of Care) n=46 Participants Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) n=47 Participants Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Percentage of Participants With Relapse	24 Percentage of participants Interval 13.0 to 38.0	28 Percentage of participants Interval 15.0 to 42.0	36 Percentage of participants Interval 23.0 to 50.0

SECONDARY outcome

Timeframe: 1 year

Progression-free and overall survival 1 year post stem cell infusion

Outcome measures

Outcome measures
Measure	Arm A (Standard of Care) n=46 Participants Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) n=47 Participants Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Percentage of Participants With Progression-free and Overall Survival Progression free survival	64 Percentage of participants	57 Percentage of participants	57 Percentage of participants
Percentage of Participants With Progression-free and Overall Survival Overall survival	72 Percentage of participants	63 Percentage of participants	70 Percentage of participants

SECONDARY outcome

Timeframe: 1 year

Rates of chronic GVHD 1 year after stem cell infusion

Outcome measures

Outcome measures
Measure	Arm A (Standard of Care) n=46 Participants Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 Participants Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) n=47 Participants Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Percentage of Participants With Chronic Graft Versus Host Disease	59 Percentage of participants	55 Percentage of participants	55 Percentage of participants

Adverse Events

Arm A (Standard of Care)

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm B (Experimental)

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm C (Experimental)

Serious events: 10 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (Standard of Care) n=46 participants at risk Drug: Tacrolimus, Methotrexate Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant	Arm B (Experimental) n=45 participants at risk Drug: Bortezomib, Tacrolimus, Methotrexate Other Names: Velcade Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant	Arm C (Experimental) n=47 participants at risk Drug: Bortezomib, Sirolimus, Tacrolimus Other Names: Velcade Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Renal and urinary disorders Acute Kidney Injury	0.00% 0/46 • 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.	2.2% 1/45 • 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.	0.00% 0/47 • 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.
Vascular disorders Deep Vein Thrombosis	0.00% 0/46 • 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.	2.2% 1/45 • 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.	4.3% 2/47 • 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) Treatment Related Secondary Malignancy	0.00% 0/46 • 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.	0.00% 0/45 • 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.	2.1% 1/47 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Neoplasm	4.3% 2/46 • 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.	6.7% 3/45 • Number of events 3 • 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.	8.5% 4/47 • Number of events 4 • 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.
Vascular disorders Hematoma	0.00% 0/46 • 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.	0.00% 0/45 • 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.	2.1% 1/47 • 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.
Nervous system disorders Intracranial Hemorrhage	2.2% 1/46 • 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.	0.00% 0/45 • 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.	0.00% 0/47 • 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.
Nervous system disorders Sinus Bradycardia	0.00% 0/46 • 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.	2.2% 1/45 • 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.	0.00% 0/47 • 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.
Metabolism and nutrition disorders Hyponatremia	2.2% 1/46 • 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.	0.00% 0/45 • 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.	0.00% 0/47 • 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.
General disorders Multi-organ failure	0.00% 0/46 • 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.	2.2% 1/45 • 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.	0.00% 0/47 • 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 Infection	2.2% 1/46 • 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.	0.00% 0/45 • 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.	0.00% 0/47 • 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.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.00% 0/46 • 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.	0.00% 0/45 • 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.	2.1% 1/47 • 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 Encephalitis infection	0.00% 0/46 • 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.	2.2% 1/45 • 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.	0.00% 0/47 • 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.
Nervous system disorders Stroke	0.00% 0/46 • 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.	2.2% 1/45 • 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.	0.00% 0/47 • 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	0.00% 0/46 • 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.	0.00% 0/45 • 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.	2.1% 1/47 • 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