Trial Outcomes & Findings for Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft vs Host Disease Following Unrelated Stem Cell Transplant (NCT NCT01790568)

Last Updated: 2018-08-13

Results Overview

GVHD Staging: Grade 2: (Skin) Maculopapular rash 25-50% BSA, (Liver) bilirubin 3.1-6mg/dl, (Gut) 1000-1500 ml/day for adult and 20-30ml/kg/day for child. Grade 3: (Skin) Maculopapular rash \>50% BSA, (Liver) 6.1-15mg/dl, (Gut) \>1500mg/day for adult and \>30ml/kg/day for child. Grade 4: (Skin) Generalized erythroderma plus bullous formation and desquamation \>5% BSA, (Liver) \>15mg/dl, (Gut) Severe abdominal pain with or without ileus, or grossly bloody stool.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

100 Days

Results posted on

2018-08-13

Participant Flow

12 patients were enrolled in the initial NCI funded portion of the Vorinostat trial (NCT1789255). 26 were enrolled to the expansion of that trial (NCT01790568). 1 pt removed prior to transplant so 25 were evaluable. All patients were treated identically. Although 26 patients were enrolled to this portion of the trial, ALL 37 are analyzed together.

Participant milestones

Participant milestones
Measure	Vorinostat NCI sponsored pilot trial of Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.	Vorinostat Expansion Expansion of the NCI sponsored pilot trial of Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Overall Study STARTED	12	26
Overall Study COMPLETED	12	25
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Vorinostat NCI sponsored pilot trial of Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.	Vorinostat Expansion Expansion of the NCI sponsored pilot trial of Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Overall Study Progression prior to transplant	0	1

Baseline Characteristics

Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft vs Host Disease Following Unrelated Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vorinostat n=37 Participants Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Age, Continuous	56 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · White, non-hispanic	33 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · White, Hispanic	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Not reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 100 Days

Outcome measures

Outcome measures
Measure	Vorinostat n=37 Participants Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Percentage of Patients That Experience Grade 2-4 GVHD Within 100 Days of Transplant	22 percentage of patients Interval 11.0 to 39.0

SECONDARY outcome

Timeframe: 1 Year

Overall survival at 1 Year.

Outcome measures

Outcome measures
Measure	Vorinostat n=37 Participants Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Percentage of Patients Alive at 1 Year	76 percentage of patients Interval 63.0 to 92.0

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure	Vorinostat n=37 Participants Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Non-Relapse Mortality Incidence	16 percentage of patients Interval 7.0 to 34.0

Adverse Events

Vorinostat

Serious events: 24 serious events

Other events: 26 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Vorinostat n=37 participants at risk Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Blood and lymphatic system disorders Anemia	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	5.4% 2/37 • Number of events 2 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Diarrhea	8.1% 3/37 • Number of events 3 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Duodenal obstruction	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Dysphagia	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Gastrointestinal disorders - Other	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Nausea	8.1% 3/37 • Number of events 3 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Vomiting	5.4% 2/37 • Number of events 2 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
General disorders Fatigue	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
General disorders Fever	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
General disorders General disorders and administration site conditions - Other	5.4% 2/37 • Number of events 2 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
General disorders Non-cardiac chest pain	8.1% 3/37 • Number of events 3 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Immune system disorders Immune system disorders - Other	16.2% 6/37 • Number of events 6 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Infections and infestations Abdominal infection	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Infections and infestations Catheter related infection	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Infections and infestations Infections and infestations - Other	10.8% 4/37 • Number of events 4 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Infections and infestations Lung infection	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Infections and infestations Urinary tract infection	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Injury, poisoning and procedural complications Fracture	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Metabolism and nutrition disorders Dehydration	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Metabolism and nutrition disorders Hyperglycemia	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	10.8% 4/37 • Number of events 4 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Nervous system disorders Radiculitis	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Renal and urinary disorders Acute kidney injury	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Vascular disorders Hypotension	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Vascular disorders Thromboembolic event	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.

Other adverse events

Other adverse events
Measure	Vorinostat n=37 participants at risk Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant. Vorinostat: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Blood and lymphatic system disorders anemia	5.4% 2/37 • Number of events 2 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Mucositis oral	8.1% 3/37 • Number of events 3 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Nausea	18.9% 7/37 • Number of events 12 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Gastrointestinal disorders Vomiting	10.8% 4/37 • Number of events 7 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
General disorders Pain	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Immune system disorders Immune system disorders - Other	5.4% 2/37 • Number of events 2 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations Alanine aminotransferase increased	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations Blood bilirubin increased	5.4% 2/37 • Number of events 3 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations Creatinine increased	16.2% 6/37 • Number of events 7 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations Lymphocyte count decreased	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations Neutrophil count decreased	13.5% 5/37 • Number of events 5 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations Platelet count decreased	35.1% 13/37 • Number of events 15 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Investigations White blood cell decreased	5.4% 2/37 • Number of events 2 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Metabolism and nutrition disorders Anorexia	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Nervous system disorders Headache	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.
Renal and urinary disorders Acute kidney injury	2.7% 1/37 • Number of events 1 • Toxicity was assessed weekly through day +100 after transplant, then monthly through day +180.

Additional Information

Dr. Pavan Reddy, M.D.

University of Michigan Comprehensive Cancer Center

Phone: 734-936-8785

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place