Trial Outcomes & Findings for A Study of Tacrolimus/Methotrexate and Tocilizumab to Prevent Acute Graft-Versus-Host Disease (AGVD) After Allogeneic Hematopoietic Stem Cell Transplant (NCT NCT02206035)
NCT ID: NCT02206035
Last Updated: 2023-03-09
Results Overview
This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
45 participants
Primary outcome timeframe
Day 180
Results posted on
2023-03-09
Participant Flow
The populations used for historical controls were not recruited by theses investigators. To obtain matched controls, the number of records analyzed exceeds the number recruited locally for the interventional arm. This investigation was conducted jointly by two research teams investigating the clinical effects, and the other investigating behavioral effects.. Each investigational team selected a population of matched historic controls appropriate to its outcome measures.
Participant milestones
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant; BCNU/carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning; total body irradiation; anti-thymocyte globulin, sirolimus; cord blood transplant; or cyclosporine/mycophenolate mofetil prophylaxis for graft versus host disease were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Overall Study
STARTED
|
45
|
130
|
204
|
|
Overall Study
COMPLETED
|
35
|
130
|
29
|
|
Overall Study
NOT COMPLETED
|
10
|
0
|
175
|
Reasons for withdrawal
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant; BCNU/carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning; total body irradiation; anti-thymocyte globulin, sirolimus; cord blood transplant; or cyclosporine/mycophenolate mofetil prophylaxis for graft versus host disease were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Overall Study
Physician Decision
|
10
|
0
|
175
|
Baseline Characteristics
Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
Baseline characteristics by cohort
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=35 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
n=130 Participants
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
n=29 Participants
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant; BCNU/carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning; total body irradiation; anti-thymocyte globulin; sirolimus; cord blood transplant; or cyclosporine/mycophenolate mofetil prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
Total
n=194 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
66 years
n=35 Participants
|
64 years
n=130 Participants
|
54 years
n=29 Participants
|
62 years
n=194 Participants
|
|
Sex: Female, Male
Known Gender · Female
|
13 Participants
n=35 Participants • Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
|
—
|
9 Participants
n=29 Participants • Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
|
22 Participants
n=64 Participants • Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
|
|
Sex: Female, Male
Known Gender · Male
|
22 Participants
n=35 Participants • Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
|
—
|
20 Participants
n=29 Participants • Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
|
42 Participants
n=64 Participants • Gender demographics was not collected for the Historical Control Arm (Primary Outcome Measure) population.
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=35 Participants
|
0 Participants
n=130 Participants
|
1 Participants
n=29 Participants
|
1 Participants
n=194 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=35 Participants
|
0 Participants
n=130 Participants
|
0 Participants
n=29 Participants
|
1 Participants
n=194 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=35 Participants
|
0 Participants
n=130 Participants
|
28 Participants
n=29 Participants
|
28 Participants
n=194 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=35 Participants
|
0 Participants
n=130 Participants
|
0 Participants
n=29 Participants
|
0 Participants
n=194 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=35 Participants
|
0 Participants
n=130 Participants
|
0 Participants
n=29 Participants
|
24 Participants
n=194 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=35 Participants
|
0 Participants
n=130 Participants
|
0 Participants
n=29 Participants
|
0 Participants
n=194 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
10 Participants
n=35 Participants
|
130 Participants
n=130 Participants
|
0 Participants
n=29 Participants
|
140 Participants
n=194 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=35 Participants
|
130 participants
n=130 Participants
|
29 participants
n=29 Participants
|
194 participants
n=194 Participants
|
PRIMARY outcome
Timeframe: Day 180Population: The Historical Control Arm (Secondary Outcome Measures) cohort was included in this study for comparison of the behavioral results (Outcome Measures 2-6). The occurrence of aGVHD was not collected for this population. The Historical Control Arm (Secondary Outcome Measures) cohort has no clinical outcome for comparison and is not included in the analysis of this outcome measure.
This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.
Outcome measures
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=35 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
n=130 Participants
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)
|
3 Participants
|
18 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 100 and Day 180Population: The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure. Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.
The measure of depressive symptoms will be determined from the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions (see Watson, 2007). The General Depression subscale of the IDAS and includes a subset of 20 five-item Likert-style questions (1= "Not at All" to 5-= "Extremely") with a scoring range of 20-100. Higher scores indicate more severe symptoms.
Outcome measures
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=25 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
n=29 Participants
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Baseline
|
34.8 units on a scale
Standard Deviation 8.8
|
—
|
38.9 units on a scale
Standard Deviation 13.0
|
|
Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Day 28
|
42.7 units on a scale
Standard Deviation 10.2
|
—
|
40.3 units on a scale
Standard Deviation 12.1
|
|
Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Day 100
|
39.5 units on a scale
Standard Deviation 9.1
|
—
|
40.4 units on a scale
Standard Deviation 14.1
|
|
Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Day 180
|
38.6 units on a scale
Standard Deviation 9.9
|
—
|
38.9 units on a scale
Standard Deviation 13.4
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 100 and Day 180Population: The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure. Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.
Levels of anxiety symptoms will be measured using the Inventory of Depression and Anxiety Symptoms (IDAS) instrument. (see Watson, 2007). Anxiety will be assessed combining two domain categories of the IDAS (panic and traumatic intrusions). There are seven 5-item, Likert-style questions responding symptom severity "during the past 2 weeks, including today ..." ranging from 'Not at all' to 'Extremely.' Scores range from 0 to 28 with higher scores indicating worse symptoms.
Outcome measures
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=25 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
n=29 Participants
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Baseline
|
16.0 units on a scale
Standard Deviation 5.19
|
—
|
15.6 units on a scale
Standard Deviation 4.5
|
|
Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Day 28
|
17.5 units on a scale
Standard Deviation 4.3
|
—
|
16.9 units on a scale
Standard Deviation 4.6
|
|
Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Day 100
|
19.2 units on a scale
Standard Deviation 6.0
|
—
|
17.4 units on a scale
Standard Deviation 4.2
|
|
Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
Day 180
|
18.6 units on a scale
Standard Deviation 6.6
|
—
|
16.9 units on a scale
Standard Deviation 4.7
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 100 and Day 180Population: The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure. Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.
Levels of fatigue symptoms will be measured using the Fatigue Symptom Inventory instrument. The FSI comprises 13 eleven-item Likert-style questions ranging from 0 = "Not at all fatigued" to 10 -"Extreme fatigue". The FSI score is the average of the individual question scores. The range of scores is 0 to 10 with higher scores indicate greater fatigue (Hann, 1998).
Outcome measures
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=25 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
n=29 Participants
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument
Baseline
|
2.4 units on a scale
Standard Deviation 1.5
|
—
|
4.1 units on a scale
Standard Deviation 2.1
|
|
Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument
Day 28
|
4.2 units on a scale
Standard Deviation 1.8
|
—
|
4.5 units on a scale
Standard Deviation 1.6
|
|
Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument
Day 100
|
3.7 units on a scale
Standard Deviation 2.0
|
—
|
4.3 units on a scale
Standard Deviation 1.9
|
|
Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument
Day 180
|
4.2 units on a scale
Standard Deviation 1.1
|
—
|
4.2 units on a scale
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 100 and Day 180Population: The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure. Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.
Levels of sleep symptoms will be measured using the Pittsburgh Sleep Quality Index instrument. The PSQI contains 19 four-item Likert-style questions conducted over a 30-day period and 5 questions rated by the bed partner or roommate. Responses range from 0 = Not in the past month to 3 = Three or more times a week. The bed partner/roommate questions were not assessed. The 19 self-rated questions are grouped into seven component domains including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. See Buysse (1989), for the scoring schema of the component domains. The PSQI score is the sum of the seven component scores and ranges from 0 to 21. Higher scores indicate poorer sleep quality.
Outcome measures
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=25 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
n=29 Participants
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument
Baseline
|
7.5 units on a scale
Standard Deviation 4.2
|
—
|
6.9 units on a scale
Standard Deviation 3.9
|
|
Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument
Day 28
|
8.1 units on a scale
Standard Deviation 4.4
|
—
|
7.8 units on a scale
Standard Deviation 4.7
|
|
Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument
Day 100
|
7.9 units on a scale
Standard Deviation 4.5
|
—
|
6.7 units on a scale
Standard Deviation 3.6
|
|
Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument
Day 180
|
8.5 units on a scale
Standard Deviation 4.0
|
—
|
7.2 units on a scale
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: Baseline, Day 28, Day 100 and Day 180Population: The Historical Control Arm (Primary Outcome Measure) cohort was included in this study for comparison of clinical results (Outcome Measure 1). Behavioral outcomes were not collected for this historical population and this cohort is not included in the analysis of this outcome measure. Ten of the treated subjects in the interventional group did not consent to participate in the biobehavioral phase of the study.
Levels of interference in activities due to pain symptoms will be measured using the Brief Pain Inventory (BPI) instrument. The BPI Interference scale is a mean of 7 eleven-item Likert-style questions with a range of 0-10 (0 = Does not interfere to 10 = Completely interferes). Higher scores indicate greater interference in daily activities due to pain symptoms (see Cleeland 1994).
Outcome measures
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=25 Participants
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m\^2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
|
Historical Control Arm (Primary Outcome Measure)
This population was derived from case reports to the Center for International Blood and Marrow Transplant Research® (Milwaukee, WI) comprising patients receiving a first allogeneic transplant at a US site excluding the Medical College of Wisconsin. Additional population details can be found in D'Souza, 2017.05.035. (n=130)
Race and ethnicity information was not collected for this control population.
|
Historical Control Arm (Secondary Outcome Measures)
n=29 Participants
This population was derived from case reports from individuals participating in a longitudinal study evaluating biobehavioral effects on recovery following allogeneic hematopoietic cell transplantation at the University of Wisconsin-Madison. Patients received prophylaxis for graft versus host disease with methotrexate/tacrolimus. No patients received tocilizumab. (n=204). Patients receiving a second transplant, BEAM conditioning (BCNU/carmustine, etoposide, cytarabine, and melphalan), total body irradiation, anti-thymocyte globulin, sirolimus, cord blood transplant, or cyclosporine/mycophenolate mofetil GVHD prophylaxis were excluded. Results presented are further limited to patients with acute myelogenous leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome to match the treatment population (n = 29).
|
|---|---|---|---|
|
Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)
Day 180
|
1.6 units on a scale
Standard Deviation 2.4
|
—
|
2.3 units on a scale
Standard Deviation 2.4
|
|
Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)
Baseline
|
1.5 units on a scale
Standard Deviation 1.7
|
—
|
1.8 units on a scale
Standard Deviation 2.1
|
|
Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)
Day 28
|
2.0 units on a scale
Standard Deviation 2.0
|
—
|
1.7 units on a scale
Standard Deviation 2.2
|
|
Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)
Day 100
|
1.6 units on a scale
Standard Deviation 1.8
|
—
|
2.2 units on a scale
Standard Deviation 2.7
|
Adverse Events
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
Serious events: 4 serious events
Other events: 35 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=35 participants at risk
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
The adverse events reported (serious and non-serious) include only those events experienced by subjects enrolled at the Medical College of Wisconsin site. Adverse events and serious adverse events were not abstracted from the databases for the two historical control populations.
|
|---|---|
|
Cardiac disorders
Chest Pain - Cardiac
|
2.9%
1/35 • Number of events 1 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Gastrointestinal disorders
Diarrhea
|
5.7%
2/35 • Number of events 2 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Gastrointestinal disorders
Mucositis oral
|
2.9%
1/35 • Number of events 1 • 12 months
Adverse events information was not collected for the historical control groups.
|
Other adverse events
| Measure |
Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)
n=35 participants at risk
Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1
Tacrolimus: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.
Methotrexate: Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
The adverse events reported (serious and non-serious) include only those events experienced by subjects enrolled at the Medical College of Wisconsin site. Adverse events and serious adverse events were not abstracted from the databases for the two historical control populations.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
65.7%
23/35 • Number of events 23 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
8.6%
3/35 • Number of events 3 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
2/35 • Number of events 2 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Cardiac disorders
Chest pain - cardiac
|
2.9%
1/35 • Number of events 1 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Gastrointestinal disorders
Mucositis oral
|
77.1%
27/35 • Number of events 27 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Infections and infestations
Sepsis
|
20.0%
7/35 • Number of events 7 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
7/35 • Number of events 7 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Investigations
Aspartate aminotransferase increased
|
2.9%
1/35 • Number of events 1 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Investigations
Blood bilirubin increased
|
2.9%
1/35 • Number of events 1 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Investigations
Creatinine increased
|
11.4%
4/35 • Number of events 4 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
45.7%
16/35 • Number of events 16 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
8.6%
3/35 • Number of events 3 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
11.4%
4/35 • Number of events 4 • 12 months
Adverse events information was not collected for the historical control groups.
|
|
Vascular disorders
Hypertension
|
14.3%
5/35 • Number of events 5 • 12 months
Adverse events information was not collected for the historical control groups.
|
Additional Information
William Drobyski, MD
Froedtert and the Medical college of Wisconsin
Phone: 414-456-4941
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place