Trial Outcomes & Findings for Maraviroc as GVHD Prophylaxis in Transplant Recipients (NCT NCT02167451)
NCT ID: NCT02167451
Last Updated: 2020-03-10
Results Overview
The ability to administer twice daily oral maraviroc in children and adults undergoing stem cell transplant in addition to routine standard graft versus host disease prophylaxis.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
31 participants
Primary outcome timeframe
Up to day +100
Results posted on
2020-03-10
Participant Flow
Participant milestones
| Measure |
Maraviroc
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Maraviroc
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Maraviroc as GVHD Prophylaxis in Transplant Recipients
Baseline characteristics by cohort
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Age, Categorical
<=18 years
|
26 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to day +100The ability to administer twice daily oral maraviroc in children and adults undergoing stem cell transplant in addition to routine standard graft versus host disease prophylaxis.
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Feasibility of Maraviroc
|
23 Participants
|
PRIMARY outcome
Timeframe: By day +100Incidence of GVHD by day+100
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
GVHD Incidence
|
11 Participants
|
PRIMARY outcome
Timeframe: Day 0pK target \>100ng/ml at day zero at the following time points : before the dose and 1, 2, 4, 6, 8, and 12 hours after maraviroc administration
Outcome measures
| Measure |
Maraviroc
n=12 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Area Under The Concentration-Time Curve (AUC) of Maraviroc
|
4805 hour *ng/mL
Standard Deviation 3265
|
PRIMARY outcome
Timeframe: day+100Population: all patients enrolled on trial
determine the number of patients who develop visceral GVHD by day+100
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Incidence of Visceral GVHD
|
6 Participants
|
PRIMARY outcome
Timeframe: Day 10pK target \>100ng/ml at day 10 at the following time points : before the dose and 1, 2, 4, 6, 8, and 12 hours after maraviroc administration
Outcome measures
| Measure |
Maraviroc
n=12 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Area Under The Concentration-Time Curve (AUC) of Maraviroc
|
5917 hour*ng/mL
Standard Deviation 4048
|
SECONDARY outcome
Timeframe: By day +100Overall survival for patients who were enrolled and received maraviroc
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Overall Survival
|
27 Participants
|
SECONDARY outcome
Timeframe: By day +100Failure to engraft and loss of graft.
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Graft Failure
|
4 Participants
|
SECONDARY outcome
Timeframe: By day +100Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Primary Disease Relapse
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day +100Incidence of toxicities due to drug
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Toxicities
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day +100Infections complications which include asymptomatic viremias for EBV, Adenovirus, CMV, and/or viral disease, bacterial and fungal infections as documented by blood cultures.
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Infectious Complications
bacterial infections
|
11 patients
|
|
Infectious Complications
Fungal infections
|
2 patients
|
|
Infectious Complications
CMV
|
5 patients
|
|
Infectious Complications
EBV
|
4 patients
|
|
Infectious Complications
Adenovirus
|
2 patients
|
|
Infectious Complications
Bk viremia
|
5 patients
|
SECONDARY outcome
Timeframe: Up to day +100Neutrophil engraftment is defined as the first of three consecutive measurements of ANC\>500mcL over 3 or more days.
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Time to Neutrophil
|
11 days
Interval 8.0 to 16.0
|
SECONDARY outcome
Timeframe: daysTime to achieve platelets count of 20,000 without transfusions
Outcome measures
| Measure |
Maraviroc
n=31 Participants
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Time to Platelet Engraftment
|
18 days
Interval 15.0 to 38.0
|
Adverse Events
Maraviroc
Serious events: 11 serious events
Other events: 16 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Maraviroc
n=31 participants at risk
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Blood and lymphatic system disorders
TMA
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Gastrointestinal disorders
Mucositis
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Gastrointestinal disorders
Colonic hemorrhage
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Hepatobiliary disorders
Autoimmune hepatitis
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
Sinusoidal Obstructive Syndrome
|
9.7%
3/31 • Number of events 3 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection- Disseminated Adenoviremia
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection- Enterobacter Aerogenes Baceteremia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection-Enterococcus Bacteremia
|
9.7%
3/31 • Number of events 3 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection-Citrobacter and Klebsiella Bacteremia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection- Klebsiella Pneumonia Bacteremia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection- Staphylococcus Aureus Bacteremia
|
9.7%
3/31 • Number of events 3 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Infection- CMV Viremia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Immune system disorders
Immune System Other (Engraftment Syndrome)
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Immune system disorders
Allergic Reaction (Angioedema)
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
Blood Bilirubin- Increased
|
16.1%
5/31 • Number of events 6 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Nervous system disorders
Altered mental status
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Psychiatric disorders
Agitation
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Renal and urinary disorders
Acute Kidney Injury
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis due to CMV
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Respiratory, thoracic and mediastinal disorders
respiratory distress
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Vascular disorders
Hypertension
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
Other adverse events
| Measure |
Maraviroc
n=31 participants at risk
Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73).
Maraviroc
|
|---|---|
|
Blood and lymphatic system disorders
anemia
|
19.4%
6/31 • Number of events 8 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Blood and lymphatic system disorders
TMA/HUS
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Gastrointestinal disorders
Mucositis
|
19.4%
6/31 • Number of events 6 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
General disorders
Fever
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Hepatobiliary disorders
Sinusoidal Obstructive Syndrome
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Immune system disorders
Allergic reaction to Ambisome
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Immune system disorders
Anaphylaxis to Cyclosporine
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Vascular disorders
Hypertension
|
9.7%
3/31 • Number of events 4 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Nervous system disorders
headache
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Metabolism and nutrition disorders
Hypokalemia
|
19.4%
6/31 • Number of events 6 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.9%
4/31 • Number of events 4 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
CMV viremia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
catheter related infection ( MSSA bacteremia, staph aureus and bacillus)
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Adenovirus in stool
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Adenovirus in blood
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
BK viremia
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Moraxella nonliquefaciens infection in blood
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
HHV6 blood
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Streptococcus infection in blood
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Klebsiella oxytoca infection in blood
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Candida in blood
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Infections and infestations
Escherichia Coli in blood
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
Neutrophil count decreased
|
38.7%
12/31 • Number of events 12 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
hemoglobin decreased
|
3.2%
1/31 • Number of events 1 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
WBC decreased
|
29.0%
9/31 • Number of events 9 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
Platelet count decreased
|
32.3%
10/31 • Number of events 12 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
Lymphocyte count decreased
|
16.1%
5/31 • Number of events 13 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
ALT increased
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
AST increased
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
Blood bilirubin increased
|
12.9%
4/31 • Number of events 4 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
|
Investigations
creatinine increased
|
6.5%
2/31 • Number of events 2 • day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
|
Additional Information
Pooja Khandelwal, MD
Cincinnati Children's Hospital Medical Center
Phone: 513-803-4762
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place