Diagnoses That Require Stem Cell Transplant, Graft Versus Host Disease (GVHD)
Conditions
Keywords
stem cell transplant, GVHD prevention
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.
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.
Interventions
DRUGMaraviroc
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 40 Years
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| GVHD Incidence | By day +100 | Incidence of GVHD by day+100 |
| 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 |
| Incidence of Visceral GVHD | day+100 | determine the number of patients who develop visceral GVHD by day+100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Overall Survival | By day +100 | Overall survival for patients who were enrolled and received maraviroc |
| Time to Platelet Engraftment | days | Time to achieve platelets count of 20,000 without transfusions |
| 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. |
| Graft Failure | By day +100 | Failure to engraft and loss of graft. |
| Primary Disease Relapse | By day +100 | — |
| Toxicities | Up to day +100 | Incidence of toxicities due to drug |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Maraviroc |
|---|---|
| Age, Categorical <=18 years | 26 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 31 |
| other Total, other adverse events | 16 / 31 |
| serious Total, serious adverse events | 11 / 31 |
Outcome results
Primary
Area Under The Concentration-Time Curve (AUC) of Maraviroc
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc | Area Under The Concentration-Time Curve (AUC) of Maraviroc | 4805 hour *ng/mL | Standard Deviation 3265 |
Primary
Area Under The Concentration-Time Curve (AUC) of Maraviroc
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc | Area Under The Concentration-Time Curve (AUC) of Maraviroc | 5917 hour*ng/mL | Standard Deviation 4048 |
Primary
Feasibility of Maraviroc
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | Feasibility of Maraviroc | 23 Participants |
Primary
GVHD Incidence
Incidence of GVHD by day+100
Time frame: By day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | GVHD Incidence | 11 Participants |
Primary
Incidence of Visceral GVHD
determine the number of patients who develop visceral GVHD by day+100
Time frame: day+100
Population: all patients enrolled on trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | Incidence of Visceral GVHD | 6 Participants |
Secondary
Graft Failure
Failure to engraft and loss of graft.
Time frame: By day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | Graft Failure | 4 Participants |
Secondary
Infectious Complications
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Infectious Complications | bacterial infections | 11 patients |
| Maraviroc | Infectious Complications | Fungal infections | 2 patients |
| Maraviroc | Infectious Complications | CMV | 5 patients |
| Maraviroc | Infectious Complications | EBV | 4 patients |
| Maraviroc | Infectious Complications | Adenovirus | 2 patients |
| Maraviroc | Infectious Complications | Bk viremia | 5 patients |
Secondary
Overall Survival
Overall survival for patients who were enrolled and received maraviroc
Time frame: By day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | Overall Survival | 27 Participants |
Secondary
Primary Disease Relapse
Time frame: By day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | Primary Disease Relapse | 0 Participants |
Secondary
Time to Neutrophil
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Time to Neutrophil | 11 days |
Secondary
Time to Platelet Engraftment
Time to achieve platelets count of 20,000 without transfusions
Time frame: days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Time to Platelet Engraftment | 18 days |
Secondary
Toxicities
Incidence of toxicities due to drug
Time frame: Up to day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc | Toxicities | 0 Participants |