Trial Outcomes & Findings for Tacrolimus and Thymoglobulin, as GvHD Prophylaxis in Patients Undergoing Related Donor HCT (NCT NCT01246206)
NCT ID: NCT01246206
Last Updated: 2018-06-18
Results Overview
Cumulative Incidence of grade II-V acute GVHD with relapse or NRM as competing risks
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Assessed first 6 months post transplant
Results posted on
2018-06-18
Participant Flow
Participant milestones
| Measure |
Tacrolimus and Thymoglobulin
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Tacrolimus and Thymoglobulin
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
|
Overall Study
Patient did not receive study regiments.
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1
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Baseline Characteristics
Tacrolimus and Thymoglobulin, as GvHD Prophylaxis in Patients Undergoing Related Donor HCT
Baseline characteristics by cohort
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
|
Age, Continuous
|
59.5 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Assessed first 6 months post transplantPopulation: All participants
Cumulative Incidence of grade II-V acute GVHD with relapse or NRM as competing risks
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Incidence of Acute GVHD
|
45.0 percentage of participants
Interval 22.3 to 65.4
|
PRIMARY outcome
Timeframe: Assessed first 6 months post transplantCounted the number of participants that experienced any type of grade 3 or higher toxicity.
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Safety Defined by Serious Adverse Events
|
19 participants
|
PRIMARY outcome
Timeframe: Assessed first 6 months post transplantPopulation: Those participants who contracted Acute GVHD
Cumulative Incidence of grade III-V acute GVHD with relapse or NRM as competing risks
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Severity of Acute GVHD
|
10.0 % of participants with sever aGVHD
Interval 1.6 to 27.8
|
SECONDARY outcome
Timeframe: Followed for up to two years post transplantPopulation: All participants
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Determine Incidence of Opportunistic Infections
|
95.0 percentage of participants
Interval 75.1 to 99.9
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SECONDARY outcome
Timeframe: Followed for up to two years post transplantPopulation: All participants
Cumulative Incidence of chronic GVHD with relapse or NRM as competing risks
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Estimate Incidence of Chronic GVHD at Two Years
|
75.0 percentage of participants
Interval 47.3 to 89.5
|
SECONDARY outcome
Timeframe: Followed for up to two years post transplantPopulation: All participants
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Overall Survival at Two Year,
|
75.0 percentage of participants
Interval 50.9 to 91.3
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SECONDARY outcome
Timeframe: Followed for up to two years post transplantPopulation: All paarticipants
The number of days until engraftment ("G500")
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Determine Time to Engraftment ("G500")
|
11 days
Interval 7.0 to 12.0
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SECONDARY outcome
Timeframe: Followed for up to two years post transplantPopulation: All paarticipants
The number of days until engraftment ("PLT20")
Outcome measures
| Measure |
Tacrolimus and Thymoglobulin
n=20 Participants
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Determine Time to Engraftment ("PLT20")
|
17 days
Interval 0.0 to 25.0
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Adverse Events
Tacrolimus and Thymoglobulin
Serious events: 19 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tacrolimus and Thymoglobulin
n=21 participants at risk
Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis
Tacrolimus and Thymoglobulin: Intravenous Tacrolimus 0.03 mg/kg/d, beginning day -3, where day 0 is the day of stem cell infusion or "transplant." Intravenous tacrolimus will be discontinued once the participant starts eating, and the drug will then be given orally at a dose of approximately 4 times the intravenous dose. Tacrolimus will be discontinued starting 100 days after transplant unless signs of acute and chronic GVHD develop or if severe toxicity occurs. Thymoglobulin will be given 0.5 mg/kg day-3, Thymoglobulin 1.5 mg/kg day -2, Thymoglobulin 2.5 mg/kg day -1. Thymoglobulin will be given intravenously over 6 hours.
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|---|---|
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Investigations
Alanine Aminotransferase increased
|
28.6%
6/21 • Number of events 6
|
|
Investigations
Aspartate Aminotransferase (AST)
|
19.0%
4/21 • Number of events 4
|
|
Renal and urinary disorders
Acute Kidney Injury
|
4.8%
1/21 • Number of events 1
|
|
Cardiac disorders
Asystole
|
4.8%
1/21 • Number of events 1
|
|
Cardiac disorders
Atrial Fibrillation
|
19.0%
4/21 • Number of events 4
|
|
Investigations
Bilirubin increase
|
19.0%
4/21 • Number of events 4
|
|
General disorders
Chills
|
9.5%
2/21 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Death
|
28.6%
6/21 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhea
|
38.1%
8/21 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Edema face
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Edema limbs
|
4.8%
1/21 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Fever
|
23.8%
5/21 • Number of events 5
|
|
Gastrointestinal disorders
Gastric Hemorrhage
|
14.3%
3/21 • Number of events 3
|
|
Investigations
High cholesterol
|
4.8%
1/21 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
4.8%
1/21 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
38.1%
8/21 • Number of events 8
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
14.3%
3/21 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
4.8%
1/21 • Number of events 1
|
|
Vascular disorders
Hypertension
|
42.9%
9/21 • Number of events 9
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
9.5%
2/21 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
9.5%
2/21 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
52.4%
11/21 • Number of events 11
|
|
Metabolism and nutrition disorders
Hypokalemia
|
23.8%
5/21 • Number of events 5
|
|
Vascular disorders
Hypotension
|
57.1%
12/21 • Number of events 12
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.8%
1/21 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
28.6%
6/21 • Number of events 6
|
|
Infections and infestations
Cytomegalovirus (CMV) infection
|
33.3%
7/21 • Number of events 7
|
|
Infections and infestations
Epstein-Barr virus (EBV) infection
|
9.5%
2/21 • Number of events 2
|
|
Infections and infestations
BK virus infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
C diff infection
|
33.3%
7/21 • Number of events 7
|
|
Infections and infestations
E coli infection
|
14.3%
3/21 • Number of events 3
|
|
Infections and infestations
E faecalis infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Enterococcus raffino infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
HSV2 Infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
K oxytoca infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Oral candida infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Staph coagulase neg
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Staph epi infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Staph not aureus
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Strep viridans infection
|
9.5%
2/21 • Number of events 2
|
|
Infections and infestations
TB infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
UTI infection
|
14.3%
3/21 • Number of events 3
|
|
Infections and infestations
Citrobacter koseri infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Adenovirus infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Aspirgillus infection
|
9.5%
2/21 • Number of events 2
|
|
Infections and infestations
Bronchial infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Catheter related infection
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Gram cocci infection
|
9.5%
2/21 • Number of events 2
|
|
Infections and infestations
Gram neg coccobacil infection
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Infusion related reaction
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
38.1%
8/21 • Number of events 8
|
|
Gastrointestinal disorders
Mucositis
|
33.3%
7/21 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
9.5%
2/21 • Number of events 2
|
|
Cardiac disorders
Myocardial infarction
|
4.8%
1/21 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
14.3%
3/21 • Number of events 3
|
|
General disorders
Pain
|
57.1%
12/21 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
14.3%
3/21 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
4.8%
1/21 • Number of events 1
|
|
Infections and infestations
Sepsis
|
14.3%
3/21 • Number of events 3
|
|
Cardiac disorders
Sinus Tachycardia
|
33.3%
7/21 • Number of events 7
|
|
Nervous system disorders
Syncope
|
14.3%
3/21 • Number of events 3
|
|
Vascular disorders
Thromboembolic event
|
9.5%
2/21 • Number of events 2
|
|
Investigations
Troponin increase
|
9.5%
2/21 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
3/21 • Number of events 3
|
|
Infections and infestations
Wound infection
|
4.8%
1/21 • Number of events 1
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Zaid Al-Kadhimi
Barbara Ann Karmanos Cancer Institute
Phone: 800-527-6266
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place