Hematopoietic Stem Cell Transplantation
Conditions
Brief summary
This is a phase II open label trial designed to evaluate the efficacy of Tac/MTX/Toc in preventing graft versus host disease (GVHD). Outcomes of patients on this clinical trial will be compared to those of contemporary controls from the CIBMTR.
Detailed description
This is a Phase II open label trial designed to evaluate the efficacy of Tacrolimus (Tac), Methotrexate (MTX) and Tocilizumab (Toc) (combined Tac/MTX/Toc) in preventing graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation compared to a contemporary control cohort selected from the Center for International Bone Marrow Transplant Research (CIBMTR) that is treated with standard methotrexate and tacrolimus for GVHD prevention. The control group of patients will satisfy similar eligibility requirements as the patients enrolled in the clinical trial and they will be matched for relevant clinical variables (age, sex, conditioning regimen, disease, graft source, etc). 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 post transplant. 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. Ancillary Study: The ancillary study will evaluate whether tocilizumab is effective at positively impacting mood, fatigue, sleep, and pain in a group of individuals undergoing allogeneic hematopoietic stem cell transplantation as compared to individuals not receiving tocilizumab. We will also assess whether tocilizumab alters gene expression and Rap1 prenylation in a manner that may reduce further progression or relapse of cancer after transplant.
Interventions
DRUGTacrolimus
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.
DRUGMethotrexate
Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.
DRUGTocilizumab
Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
Sponsors
William R. Drobyski, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disease and myelodysplasia with less than 5% of blasts in the bone marrow 3. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, Non-Hodgkin Lymphoma or Hodgkin Disease with chemosensitive disease at time of transplant 4. Planned conditioning regimens including combination of busulfan and fludarabine or busulfan and cyclophosphamide 5. Transplantation with T-cell-replete grafts 6. Bone marrow or mobilized peripheral blood cell grafts 7. Patients must have either a sibling donor (6/6 match at human leukocyte antigens (HLA-A, -B and -DRB1) or a unrelated donor (8/8 match at HLA-A, -B, -C and -DRB1) 8. Cardiac function: Ejection fraction at rest \>45% for myeloablative conditioning or \>40% for reduced intensity conditioning 9. Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight) 10. Pulmonary function: Diffusing Capacity of Lung for Carbon Monoxide (DLCO) ≥40% (adjusted for hemoglobin) and FEV1≥50% 11. Liver function: total bilirubin \< 1.5 x the upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \< 2.5x the upper normal limit 12. Signed informed consent
Exclusion criteria
1. Prior allogeneic hematopoietic cell transplant (HCT) 2. Karnofsky Performance Score \<70% 3. Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression of infectious disease or no clinical improvement) at time of enrollment 4. Prior intolerance or allergy to Tocilizumab 5. Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody at time of conditioning regimen 6. History of diverticulitis, Crohn's disease or ulcerative colitis 7. History of demyelinating disorder 8. Pregnant and lactating women 9. Patients with a history of rheumatologic disorders who have previously received Tocilizumab Eligibility for the Control Arm Patients in the control arm will be identified from patients reported to the CIBMTR from U.S centers. Control patients will be required to satisfy similar eligibility requirements as patients being enrolled in the clinical trial. Patients will need to fulfill the same inclusion criteria for the clinical trial according to Section 2.4.1, plus the following: 1. Receive Tac/MTX as the sole GVHD prophylaxis approach 2. Receive the same regimens as specified in Table 2.5 3. Year of transplant from 2010 to 2013
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD) | Day 180 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Baseline, Day 28, Day 100 and Day 180 | 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. |
| Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Baseline, Day 28, Day 100 and Day 180 | 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. |
| Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Baseline, Day 28, Day 100 and Day 180 | 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). |
| Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Baseline, Day 28, Day 100 and Day 180 | 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. |
| Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Baseline, Day 28, Day 100 and Day 180 | 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). |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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/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. | 35 |
| 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. | 130 |
| 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 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). | 29 |
| Total | 194 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 10 | 0 | 175 |
Baseline characteristics
| Characteristic | Total | Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Historical Control Arm (Primary Outcome Measure) | Historical Control Arm (Secondary Outcome Measures) |
|---|---|---|---|---|
| Age, Continuous | 62 years | 66 years | 64 years | 54 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 28 Participants | 0 Participants | 0 Participants | 28 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 140 Participants | 10 Participants | 130 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 24 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 194 participants | 35 participants | 130 participants | 29 participants |
| Sex: Female, Male Known Gender Female | 22 Participants | 13 Participants | — | 9 Participants |
| Sex: Female, Male Known Gender Male | 42 Participants | 22 Participants | — | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 35 |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 4 / 35 |
Outcome results
Primary
Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)
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.
Time frame: Day 180
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD) | 3 Participants |
| Historical Control Arm (Primary Outcome Measure) | Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD) | 18 Participants |
| Historical Control Arm (Secondary Outcome Measures) | Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD) | 0 Participants |
Secondary
Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
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.
Time frame: Baseline, Day 28, Day 100 and Day 180
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Day 180 | 16.9 units on a scale | Standard Deviation 4.7 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Baseline | 15.6 units on a scale | Standard Deviation 4.5 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Day 100 | 17.4 units on a scale | Standard Deviation 4.2 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Day 28 | 16.9 units on a scale | Standard Deviation 4.6 |
Comparison: Comparison at Baselinep-value: 0.99t-test, 2 sided
Comparison: Comparison at Day 28p-value: 0.48t-test, 2 sided
p-value: 0.35t-test, 2 sided
Comparison: Comparison at Day 180p-value: 0.96t-test, 2 sided
Secondary
Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument
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.
Time frame: Baseline, Day 28, Day 100 and Day 180
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | 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 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Day 180 | 38.9 units on a scale | Standard Deviation 13.4 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Baseline | 38.9 units on a scale | Standard Deviation 13 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Day 100 | 40.4 units on a scale | Standard Deviation 14.1 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument | Day 28 | 40.3 units on a scale | Standard Deviation 12.1 |
Comparison: Comparison at Baselinep-value: 0.95t-test, 2 sided
Comparison: Comparison at Day 28p-value: 0.26t-test, 2 sided
Comparison: Comparison at Day 100p-value: 0.63t-test, 2 sided
Comparison: Comparison at Day 180p-value: 0.76t-test, 2 sided
Secondary
Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument
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).
Time frame: Baseline, Day 28, Day 100 and Day 180
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Baseline | 2.4 units on a scale | Standard Deviation 1.5 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Day 28 | 4.2 units on a scale | Standard Deviation 1.8 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Day 100 | 3.7 units on a scale | Standard Deviation 2 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Day 180 | 4.2 units on a scale | Standard Deviation 1.1 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Day 180 | 4.2 units on a scale | Standard Deviation 1.6 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Baseline | 4.1 units on a scale | Standard Deviation 2.1 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Day 100 | 4.3 units on a scale | Standard Deviation 1.9 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument | Day 28 | 4.5 units on a scale | Standard Deviation 1.6 |
Comparison: Comparison at Baselinep-value: <0.001t-test, 2 sided
Comparison: Comparison at Day 28p-value: 0.75t-test, 2 sided
Comparison: Comparison at Day 100p-value: 0.28t-test, 2 sided
Comparison: Comparison at Day 180p-value: 0.82t-test, 2 sided
Secondary
Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)
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).
Time frame: Baseline, Day 28, Day 100 and Day 180
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Day 28 | 2.0 units on a scale | Standard Deviation 2 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Baseline | 1.5 units on a scale | Standard Deviation 1.7 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Day 180 | 1.6 units on a scale | Standard Deviation 2.4 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Day 100 | 1.6 units on a scale | Standard Deviation 1.8 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Day 180 | 2.3 units on a scale | Standard Deviation 2.4 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Baseline | 1.8 units on a scale | Standard Deviation 2.1 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Day 28 | 1.7 units on a scale | Standard Deviation 2.2 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference) | Day 100 | 2.2 units on a scale | Standard Deviation 2.7 |
Comparison: Comparison at Baselinep-value: 0.1t-test, 2 sided
Comparison: Comparison at Day 28p-value: 0.32t-test, 2 sided
Comparison: Comparison at Day 100p-value: 0.63t-test, 2 sided
Comparison: Comparison at Day 180p-value: 0.3t-test, 2 sided
Secondary
Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument
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.
Time frame: Baseline, Day 28, Day 100 and Day 180
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Baseline | 7.5 units on a scale | Standard Deviation 4.2 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Day 28 | 8.1 units on a scale | Standard Deviation 4.4 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Day 100 | 7.9 units on a scale | Standard Deviation 4.5 |
| Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Day 180 | 8.5 units on a scale | Standard Deviation 4 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Day 180 | 7.2 units on a scale | Standard Deviation 3.9 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Baseline | 6.9 units on a scale | Standard Deviation 3.9 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Day 100 | 6.7 units on a scale | Standard Deviation 3.6 |
| Historical Control Arm (Secondary Outcome Measures) | Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument | Day 28 | 7.8 units on a scale | Standard Deviation 4.7 |
Comparison: Comparison at Baselinep-value: 0.54t-test, 2 sided
Comparison: Comparison at Day 28p-value: 0.61t-test, 2 sided
Comparison: Comparison at Day 100p-value: 0.42t-test, 2 sided
Comparison: Comparison at Day 180p-value: 0.38t-test, 2 sided