Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation
Conditions
Keywords
Graft-versus-host disease, GVHD, Maraviroc, non-myeloablative allogeneic stem-cell transplantation, Hematopoietic stem cell transplantation
Brief summary
This study investigates the effectiveness and safety of Maraviroc (an oral medication given twice daily given in addition to the standard GVHD prophylaxis) in preventing Graft versus Host Disease (GVHD) in patients undergoing non-myeloablative allogeneic stem-cell transplantation (SCT). Subjects will receive Maraviroc bid (in addition to standard GVHD prophylaxis) beginning after the last dose of the chemotherapy conditioning regimen until day 30 after stem-cell infusion.
Interventions
DRUGMaraviroc 150 MG
Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.
DRUGMaraviroc 300 mg
Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.
DRUGMaraviroc 300 mg Phase II
Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients scheduled to undergo non-myeloablative allogeneic stem-cell transplantation. * meet institutional eligibility criteria for allogeneic SCT. Significant criteria are: * Renal function: Serum creatinine \<2; or calculated creatinine clearance \> 40 mL/min/1.72m2; * Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal; * Pulmonary disease: FVC or FEV1 \> 40% predicted; Cardiac ejection fraction \> 40%.
Exclusion criteria
* Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant * Patients who are not undergoing standard non-myeloablative SCT with Flu/Bu conditioning and Tax/MTX GVHD prophylaxis * Patients with uncontrolled bacterial, viral or fungal infections * Patients who take strong inducers or inhibitors of the CYP450A4 * Patients receiving other investigational drugs for GVHD * Women who are pregnant, plan to become pregnant or are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Maraviroc | 1 year | number of Adverse Events following exposure to Maraviroc |
| Efficacy of Maraviroc | 8 weeks | Efficacy is measured by number of participants progressing to acute GVHD. If acute GVHD is noted in a participant following exposure to study drug, then efficacy was not achieved. If no GVHD was noted following exposure, then efficacy was achieved in that participant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT | pre-dose, 1,2,3,4,6,12 hours post-dose | Plasma maraviroc levels were measured in the blood with a target level of 100 ng per milliliter. Blood was drawn on Day 0 and Day 10-12 at pre-dose, 1, 2, 3, 4, 6, and 12 hours post-dose. Data was analyzed looking at the number of patients to achieve the target of 100 ng per milliliter at any time point. |
| Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD | 1 year | count of how many patients treated with Maraviroc during SCT go on to develop chronic GVHD in 1 year |
| Rate of Early Mortality After Transplant | 1 year | Number of participants who died without relapse within 1 year of SCT |
| Number of Participants Who Relapsed During Study Period | 1 year and 11 months | Number of participants who received Maraviroc during SCT who relapsed within 1 year and 11 months. This was based on a diagnosis made by their physician that their primary cancer had returned. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: 150mg Maraviroc 150mg twice daily
Maraviroc 150 MG: Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion. | 7 |
| Phase 1: 300mg Maraviroc 300mg twice daily
Maraviroc 300 mg: Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion. | 6 |
| Phase 2: 300mg Maraviroc 300mg twice daily
Maraviroc 300 mg: Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion. | 25 |
| Total | 38 |
Baseline characteristics
| Characteristic | Phase 1: 150mg Maraviroc | Phase 1: 300mg Maraviroc | Phase 2: 300mg Maraviroc | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 10 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 15 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 23 Participants | 36 Participants |
| Region of Enrollment United States | 7 participants | 6 participants | 25 participants | 38 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 10 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 15 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 17 / 25 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 25 |
Outcome results
Primary
Efficacy of Maraviroc
Efficacy is measured by number of participants progressing to acute GVHD. If acute GVHD is noted in a participant following exposure to study drug, then efficacy was not achieved. If no GVHD was noted following exposure, then efficacy was achieved in that participant
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 150mg Maraviroc | Efficacy of Maraviroc | 0 Participants |
| Phase 1: 300mg Maraviroc | Efficacy of Maraviroc | 0 Participants |
| Phase 2: 300mg Maraviroc | Efficacy of Maraviroc | 0 Participants |
Primary
Safety of Maraviroc
number of Adverse Events following exposure to Maraviroc
Time frame: 1 year
Population: patients receiving SCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 150mg Maraviroc | Safety of Maraviroc | 8 Number of AEs |
| Phase 1: 300mg Maraviroc | Safety of Maraviroc | 6 Number of AEs |
| Phase 2: 300mg Maraviroc | Safety of Maraviroc | 18 Number of AEs |
Secondary
Number of Participants Who Relapsed During Study Period
Number of participants who received Maraviroc during SCT who relapsed within 1 year and 11 months. This was based on a diagnosis made by their physician that their primary cancer had returned.
Time frame: 1 year and 11 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 150mg Maraviroc | Number of Participants Who Relapsed During Study Period | 2 Participants |
| Phase 1: 300mg Maraviroc | Number of Participants Who Relapsed During Study Period | 2 Participants |
| Phase 2: 300mg Maraviroc | Number of Participants Who Relapsed During Study Period | 15 Participants |
Secondary
Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD
count of how many patients treated with Maraviroc during SCT go on to develop chronic GVHD in 1 year
Time frame: 1 year
Population: Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 150mg Maraviroc | Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD | 1 Participants |
| Phase 1: 300mg Maraviroc | Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD | 3 Participants |
| Phase 2: 300mg Maraviroc | Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD | 2 Participants |
Secondary
Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT
Plasma maraviroc levels were measured in the blood with a target level of 100 ng per milliliter. Blood was drawn on Day 0 and Day 10-12 at pre-dose, 1, 2, 3, 4, 6, and 12 hours post-dose. Data was analyzed looking at the number of patients to achieve the target of 100 ng per milliliter at any time point.
Time frame: pre-dose, 1,2,3,4,6,12 hours post-dose
Population: not enough data was collected to reach statistical power for plasma maraviroc levels in the Phase 2 group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 150mg Maraviroc | Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT | 4 number of patients to reach target |
| Phase 1: 300mg Maraviroc | Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT | 6 number of patients to reach target |
| Phase 2: 300mg Maraviroc | Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT | 0 number of patients to reach target |
Secondary
Rate of Early Mortality After Transplant
Number of participants who died without relapse within 1 year of SCT
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: 150mg Maraviroc | Rate of Early Mortality After Transplant | 2 Participants |
| Phase 1: 300mg Maraviroc | Rate of Early Mortality After Transplant | 0 Participants |
| Phase 2: 300mg Maraviroc | Rate of Early Mortality After Transplant | 4 Participants |