Trial Outcomes & Findings for Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies (NCT NCT01789255)
NCT ID: NCT01789255
Last Updated: 2018-07-24
Results Overview
The incidence of grade 2-4 acute GVHD (Graft Versus Host Disease) by day 100 Grade 2 GVHD: Maculopapular rash covering 25-50% of BSA (Body Surface Area), bilirubin between 3.1-6 mg/dl, and/ or adult stool output between 1000-1500 ml/day (child between 20-30 ml/kg/day). Grade 3 GVHD: Maculopapular rash covering \>50% of BSA, bilirubin between 6.1-15 mg/dl, and/ or adult stool output \>1500 ml/day (child \>30 ml/kg/day). Grade 4 GVHD: Generalized erythroderma plus bullous formation and desquamation \>5% BSA, bilirubin \>15 mg/dl, and/ or severe abdominal pain with or without ileus, or grossly bloody stool.
COMPLETED
PHASE2
12 participants
Day 100
2018-07-24
Participant Flow
Participant milestones
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Overall Study
STARTED
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12
|
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Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies
Baseline characteristics by cohort
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=12 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Age, Continuous
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49 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 100The incidence of grade 2-4 acute GVHD (Graft Versus Host Disease) by day 100 Grade 2 GVHD: Maculopapular rash covering 25-50% of BSA (Body Surface Area), bilirubin between 3.1-6 mg/dl, and/ or adult stool output between 1000-1500 ml/day (child between 20-30 ml/kg/day). Grade 3 GVHD: Maculopapular rash covering \>50% of BSA, bilirubin between 6.1-15 mg/dl, and/ or adult stool output \>1500 ml/day (child \>30 ml/kg/day). Grade 4 GVHD: Generalized erythroderma plus bullous formation and desquamation \>5% BSA, bilirubin \>15 mg/dl, and/ or severe abdominal pain with or without ileus, or grossly bloody stool.
Outcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=12 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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The Number of Participants That Experience Grade 2-4 Acute GVHD (Graft Versus Host Disease) by Day 100
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2 participants
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SECONDARY outcome
Timeframe: Up to day 30The addition of vorinostat to tacrolimus and methotrexate for GVHD prophylaxis will be considered feasible if 60% or more of the planned doses are administered.
Outcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=12 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Mean Percent of Planned Dose Administered
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82.5 percent of dose administered
Interval 53.8 to 100.0
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SECONDARY outcome
Timeframe: Up to 1 yearPopulation: This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
The percentage of patients alive without GVHD or use of steroids at 1 year.
Outcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=37 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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The Percentage of Patients Alive Without GVHD or Use of Steroids
|
47 percentage of patients
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SECONDARY outcome
Timeframe: Up to 1 yearPopulation: This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
The percentage of patients alive at 1 year
Outcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=37 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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The Percentage of Patients Alive at 1 Year
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76 percentage of patients
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SECONDARY outcome
Timeframe: Up to 1 yearOutcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=12 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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The Percentage of Patients With Relapse at 1 Year
|
19 percentage of patients
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SECONDARY outcome
Timeframe: Up to day 100Population: This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
Median Ac-H3 levels ( depicted as a ratio of ac-H2 optical density (OD) and beta actin OD) were compared in patients treated with Vorinostat to patients not treated with Vorinostat. Optical Density is a dimensionless unit.
Outcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=37 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Median Ac-H3 Levels in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
Treated with Vorinostat
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0.943 Ratio
Interval 0.42 to 1.27
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Median Ac-H3 Levels in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
Not Treated with Vorinostat
|
0.679 Ratio
Interval 0.19 to 1.01
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SECONDARY outcome
Timeframe: Up to day 100Population: This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
Median plasma concentration of IL-6 (Interleukin-6 cytokine) was compared in patients treated with Vorinostat to those not treated with Vorinostat.
Outcome measures
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=37 Participants
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Median Plasma Concentration of IL-6 in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
Treated with Vorinostat
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4.2 pg/mL
Interval 0.1 to 22.3
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Median Plasma Concentration of IL-6 in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
Not Treated with Vorinostat
|
7.6 pg/mL
Interval 0.3 to 70.1
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Adverse Events
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
Serious adverse events
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=12 participants at risk
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Blood and lymphatic system disorders
Anemia
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8.3%
1/12 • Number of events 1
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Gastrointestinal disorders
Diarrhea
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25.0%
3/12 • Number of events 3
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|
Gastrointestinal disorders
Dysphagia
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8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Number of events 1
|
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General disorders
Non-cardiac chest pain
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16.7%
2/12 • Number of events 2
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Immune system disorders
Immune system disorders, Other
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8.3%
1/12 • Number of events 1
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|
Infections and infestations
Abdominal infection
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8.3%
1/12 • Number of events 1
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|
Infections and infestations
Catheter related infection
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8.3%
1/12 • Number of events 1
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|
Infections and infestations
Urinary tract infection
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8.3%
1/12 • Number of events 1
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|
Metabolism and nutrition disorders
Dehydration
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8.3%
1/12 • Number of events 1
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified, Other
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25.0%
3/12 • Number of events 3
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|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.3%
1/12 • Number of events 1
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Other adverse events
| Measure |
Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
n=12 participants at risk
Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
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|---|---|
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Blood and lymphatic system disorders
Anemia
|
16.7%
2/12 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
4/12 • Number of events 4
|
|
Gastrointestinal disorders
Dysphagia
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
25.0%
3/12 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
25.0%
3/12 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
3/12 • Number of events 4
|
|
General disorders
Non-cardiac chest pain
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16.7%
2/12 • Number of events 2
|
|
General disorders
Pain
|
8.3%
1/12 • Number of events 1
|
|
Immune system disorders
Immune system disorders, Other
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Abdominal infection
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Catheter related infection
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Blood bilirubin increased
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16.7%
2/12 • Number of events 3
|
|
Investigations
Creatinine increased
|
33.3%
4/12 • Number of events 5
|
|
Investigations
Lymphocyte count decreased
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Platelet count decreased
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66.7%
8/12 • Number of events 8
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|
Investigations
White blood cell decreased
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16.7%
2/12 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
1/12 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified, Other
|
25.0%
3/12 • Number of events 3
|
|
Renal and urinary disorders
Acute kidney injury
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.3%
1/12 • Number of events 1
|
Additional Information
Pavan Reddy, M.D.
University of Michigan Comprehensive Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60