Maraviroc as GVHD Prophylaxis in Transplant Recipients

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02167451
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arm: 1
• Duration (Months): 50
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose is to determine if the addition of Maraviroc to a standard transplant regimen will reduce the incidence of graft versus host disease in children and young adults after a stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Diagnoses That Require Stem Cell Transplant; Graft Versus Host Disease (GVHD)	Drug: Maraviroc	Phase 1/Phase 2

Detailed Description

In the first stage, drug levels will be obtained to establish appropriate dosing. In the second stage of the study the investigators will study the effects of using Maraviroc in these patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Maraviroc as Graft Versus Host Disease Prophylaxis in Pediatric and Adult Stem Cell Transplant Recipients
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Sep 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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).

Drug: Maraviroc; Other Names: Selzentry

Outcome Measures

Primary Outcome Measures

1. Feasibility of Maraviroc [Up to day +100]

   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.

2. GVHD Incidence [By day +100]

   Incidence of GVHD by day+100

3. Area Under The Concentration-Time Curve (AUC) of Maraviroc [Day 0]

   pK 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

4. Incidence of Visceral GVHD [day+100]

   determine the number of patients who develop visceral GVHD by day+100

5. Area Under The Concentration-Time Curve (AUC) of Maraviroc [Day 10]

   pK 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

Secondary Outcome Measures

1. Overall Survival [By day +100]

   Overall survival for patients who were enrolled and received maraviroc

2. Graft Failure [By day +100]

   Failure to engraft and loss of graft.

3. Primary Disease Relapse [By day +100]

4. Toxicities [Up to day +100]

   Incidence of toxicities due to drug

5. Infectious Complications [Up to day +100]

   Infections complications which include asymptomatic viremias for EBV, Adenovirus, CMV, and/or viral disease, bacterial and fungal infections as documented by blood cultures.

6. Time to Neutrophil [Up to day +100]

   Neutrophil engraftment is defined as the first of three consecutive measurements of ANC>500mcL over 3 or more days.

7. Time to Platelet Engraftment [days]

   Time to achieve platelets count of 20,000 without transfusions

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ages 5 years and </= 40 years

• All diagnoses

• Peripheral blood stem cells, marrow or cord blood

• All conditioning regimens

• Patient must be planned to receive a calcineurin inhibitor (cyclosporine or tacrolimus) together with steroid, methotrexate or mycophenolate mofetil as GVHD prophylaxis.

Exclusion Criteria:

• Documented anaphylaxis to Maraviroc

• Ex vivo T-cell (type of white blood cell) depleted grafts

• Abnormal Alanine Aminotransferase (ALT) (>/=10X ULN) on day -3. (Assessed at study enrollment and confirmed again prior to the first dose of maraviroc.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: Pooja Khandelwal, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 23, 2018

More Information

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT02167451
• Other Study ID Numbers: 2014-1221
• First Posted: Jun 19, 2014
• Last Update Posted: Mar 10, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Children's Hospital Medical Center, Cincinnati: stem cell transplant; GVHD prevention
• Additional relevant MeSH terms: Graft vs Host Disease; Maraviroc

Study Results

Participant Flow

Arm/Group Title	Maraviroc
Arm/Group Description	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
Period Title: Overall Study
STARTED	31
COMPLETED	30
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Maraviroc
Arm/Group Description	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 Participants	31
Age (Count of Participants)
<=18 years	26 83.9%
Between 18 and 65 years	5 16.1%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	12 38.7%
Male	19 61.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.2%
Native Hawaiian or Other Pacific Islander	2 6.5%
Black or African American	0 0%
White	27 87.1%
More than one race	1 3.2%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	31 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Maraviroc
Description	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.
Time Frame	Up to day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	23 74.2%

2. Primary Outcome

Title	GVHD Incidence
Description	Incidence of GVHD by day+100
Time Frame	By day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	11 35.5%

3. Primary Outcome

Title	Area Under The Concentration-Time Curve (AUC) of Maraviroc
Description	pK 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
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	12
Mean (Standard Deviation) [hour *ng/mL]	4805 (3265)

4. Primary Outcome

Title	Incidence of Visceral GVHD
Description	determine the number of patients who develop visceral GVHD by day+100
Time Frame	day+100

Outcome Measure Data

Analysis Population Description

all patients enrolled on trial

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	6 19.4%

5. Primary Outcome

Title	Area Under The Concentration-Time Curve (AUC) of Maraviroc
Description	pK 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
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	12
Mean (Standard Deviation) [hour*ng/mL]	5917 (4048)

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival for patients who were enrolled and received maraviroc
Time Frame	By day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	27 87.1%

7. Secondary Outcome

Title	Graft Failure
Description	Failure to engraft and loss of graft.
Time Frame	By day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	4 12.9%

8. Secondary Outcome

Title	Primary Disease Relapse
Time Frame	By day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	0 0%

9. Secondary Outcome

Title	Toxicities
Description	Incidence of toxicities due to drug
Time Frame	Up to day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Count of Participants [Participants]	0 0%

10. Secondary Outcome

Title	Infectious Complications
Description	Infections complications which include asymptomatic viremias for EBV, Adenovirus, CMV, and/or viral disease, bacterial and fungal infections as documented by blood cultures.
Time Frame	Up to day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
bacterial infections	11
Fungal infections	2
CMV	5
EBV	4
Adenovirus	2
Bk viremia	5

11. Secondary Outcome

Title	Time to Neutrophil
Description	Neutrophil engraftment is defined as the first of three consecutive measurements of ANC>500mcL over 3 or more days.
Time Frame	Up to day +100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Median (Full Range) [days]	11

12. Secondary Outcome

Title	Time to Platelet Engraftment
Description	Time to achieve platelets count of 20,000 without transfusions
Time Frame	days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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
Measure Participants	31
Median (Full Range) [days]	18

Adverse Events

Time Frame	day+ 100 after BMT or 30 days after last maraviroc administration if patients withdrew from study
Arm/Group Title	Maraviroc
Arm/Group Description	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
All Cause Mortality
	Maraviroc
	Affected / at Risk (%)	# Events
Total	4/31 (12.9%)
Serious Adverse Events
	Maraviroc
	Affected / at Risk (%)	# Events
Total	11/31 (35.5%)
Blood and lymphatic system disorders
TMA	1/31 (3.2%)	1
Gastrointestinal disorders
Mucositis	1/31 (3.2%)	1
Colonic hemorrhage	1/31 (3.2%)	1
Hepatobiliary disorders
Autoimmune hepatitis	1/31 (3.2%)	1
Immune system disorders
Immune System Other (Engraftment Syndrome)	2/31 (6.5%)	2
Allergic Reaction (Angioedema)	1/31 (3.2%)	1
Infections and infestations
Infection- Disseminated Adenoviremia	2/31 (6.5%)	2
Infection- Enterobacter Aerogenes Baceteremia	1/31 (3.2%)	1
Infection-Enterococcus Bacteremia	3/31 (9.7%)	3
Infection-Citrobacter and Klebsiella Bacteremia	1/31 (3.2%)	1
Infection- Klebsiella Pneumonia Bacteremia	1/31 (3.2%)	1
Infection- Staphylococcus Aureus Bacteremia	3/31 (9.7%)	3
Infection- CMV Viremia	1/31 (3.2%)	1
Investigations
Sinusoidal Obstructive Syndrome	3/31 (9.7%)	3
Blood Bilirubin- Increased	5/31 (16.1%)	6
Nervous system disorders
Altered mental status	2/31 (6.5%)	2
Psychiatric disorders
Agitation	1/31 (3.2%)	1
Renal and urinary disorders
Acute Kidney Injury	2/31 (6.5%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/31 (3.2%)	1
Pneumonia	1/31 (3.2%)	1
Pneumonitis due to CMV	1/31 (3.2%)	1
respiratory distress	2/31 (6.5%)	2
Vascular disorders
Hypertension	1/31 (3.2%)	1
Other (Not Including Serious) Adverse Events
	Maraviroc
	Affected / at Risk (%)	# Events
Total	16/31 (51.6%)
Blood and lymphatic system disorders
anemia	6/31 (19.4%)	8
TMA/HUS	1/31 (3.2%)	1
Gastrointestinal disorders
Mucositis	6/31 (19.4%)	6
General disorders
Fever	1/31 (3.2%)	1
Hepatobiliary disorders
Sinusoidal Obstructive Syndrome	1/31 (3.2%)	1
Immune system disorders
Allergic reaction to Ambisome	1/31 (3.2%)	1
Anaphylaxis to Cyclosporine	1/31 (3.2%)	1
Infections and infestations
CMV viremia	1/31 (3.2%)	1
catheter related infection ( MSSA bacteremia, staph aureus and bacillus)	1/31 (3.2%)	1
Adenovirus in stool	1/31 (3.2%)	1
Adenovirus in blood	2/31 (6.5%)	2
BK viremia	1/31 (3.2%)	1
Moraxella nonliquefaciens infection in blood	1/31 (3.2%)	1
HHV6 blood	1/31 (3.2%)	1
Streptococcus infection in blood	1/31 (3.2%)	1
Klebsiella oxytoca infection in blood	1/31 (3.2%)	1
Candida in blood	1/31 (3.2%)	1
Escherichia Coli in blood	1/31 (3.2%)	1
Investigations
Neutrophil count decreased	12/31 (38.7%)	12
hemoglobin decreased	1/31 (3.2%)	1
WBC decreased	9/31 (29%)	9
Platelet count decreased	10/31 (32.3%)	12
Lymphocyte count decreased	5/31 (16.1%)	13
ALT increased	2/31 (6.5%)	2
AST increased	2/31 (6.5%)	2
Blood bilirubin increased	4/31 (12.9%)	4
creatinine increased	2/31 (6.5%)	2
Metabolism and nutrition disorders
Hypokalemia	6/31 (19.4%)	6
Hyperglycemia	4/31 (12.9%)	4
Hyperkalemia	2/31 (6.5%)	2
Hypophosphatemia	1/31 (3.2%)	1
Hypocalcemia	2/31 (6.5%)	2
Hypertriglyceridemia	1/31 (3.2%)	1
Nervous system disorders
headache	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/31 (3.2%)	1
Vascular disorders
Hypertension	3/31 (9.7%)	4

Limitations/Caveats

early termination leading to small number of subjects analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.