Graft Versus Host Disease
Conditions
Brief summary
The objective of this study is to evaluate feasibility, toxicity and efficacy of using Rapamycin to prevent chronic graft-versus-host-disease (GVHD) during and after the tacrolimus taper in recipients of allogeneic stem cell transplant. Our hypothesis is that the T cells that can cause chronic GVHD are suppressed but not eliminated by calcineurin inhibitors. Therefore, when the calcineurin inhibitors are discontinued, the T cells may get activated and result in GVHD. Rapamycin on the other hand will allow anergy formation and thus when discontinued, T cells should not get activated. The schedule is designed to have therapeutic rapamycin levels as the tacrolimus is discontinued. Rapamycin will be continued as a single agent for additional 4 weeks and be tapered off in two weeks.
Interventions
DRUGRapamycin
Rapamycin will be initiated 24 weeks post SCT, while the patient is on Tacrolimus. The initial dose of rapamycin is 12 mg of loading dose, followed by 4 mg daily. The dose will be adjusted to keep trough level at 3-12 ng/dl. Rapamycin will be continued at the therapeutic dose for 4 additional weeks after Tacrolimus is stopped. Rapamycin will then be tapered off over 2 weeks. The patients will be on 50% of steady state dose for one week and 25% of the steady state dose for the last week.
DRUGTacrolimus
Tacrolimus target level is 5-10 ng/dl. Tacrolimus taper will start at 26 weeks post SCT. Tacrolimus will be tapered off over 4-8 weeks. The rate of taper will be 25% every to weeks for patients on 4 mg or more tacrolimus daily. For the patients on 3 mg or less of tacrolimus, the dose will be reduced 1 mg every two weeks, and the last dose will be 1 mg every other day for two weeks.
Sponsors
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Received an allogeneic MSD or MUD PBSCT * 24 weeks post SCT * Currently on Tacrolimus for GVHD prophylaxis * Deemed eligible for tapering off of Tacrolimus by primary BMT physician
Exclusion criteria
* Relapsed Disease * Ongoing GVHD * Patients whose immunosuppression is being stopped early to treat or prevent relapse * Patients with pure red cell aplasia due to ABO mismatched donor * Ongoing thrombotic microangiopathy * Allergy to rapamycin * Women of childbearing potential must have a negative serum pregnancy test performed prior to the start of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of the Rate of Graft Versus Host Disease (GVHD) From the Accepted Rate of 74%. | up to 8 weeks | Percentage of patients free from graft versus host disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | up to 10 weeks | achieved overall survival in regard to leukemia |
| Disease Free Survival | up to 10 weeks | achieved disease free in regard to leukemia |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rapamycin Study Arm Rapamycin: Rapamycin will be initiated 24 weeks post SCT, while the patient is on Tacrolimus. The initial dose of rapamycin is 12 mg of loading dose, followed by 4 mg daily. The dose will be adjusted to keep trough level at 3-12 ng/dl. Rapamycin will be continued at the therapeutic dose for 4 additional weeks after Tacrolimus is stopped. Rapamycin will then be tapered off over 2 weeks. The patients will be on 50% of steady state dose for one week and 25% of the steady state dose for the last week.
Tacrolimus: Tacrolimus target level is 5-10 ng/dl. Tacrolimus taper will start at 26 weeks post SCT. Tacrolimus will be tapered off over 4-8 weeks. The rate of taper will be 25% every to weeks for patients on 4 mg or more tacrolimus daily. For the patients on 3 mg or less of tacrolimus, the dose will be reduced 1 mg every two weeks, and the last dose will be 1 mg every other day for two weeks. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Rapamycin Study Arm |
|---|---|
| Age, Customized | 46 years |
| Gender Female | 0 Participants |
| Gender Male | 2 Participants |
| Region of Enrollment United States | 2 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Improvement of the Rate of Graft Versus Host Disease (GVHD) From the Accepted Rate of 74%.
Percentage of patients free from graft versus host disease
Time frame: up to 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Population | Improvement of the Rate of Graft Versus Host Disease (GVHD) From the Accepted Rate of 74%. | 0 percentage of patients |
Secondary
Disease Free Survival
achieved disease free in regard to leukemia
Time frame: up to 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Population | Disease Free Survival | 2 participants |
Secondary
Overall Survival
achieved overall survival in regard to leukemia
Time frame: up to 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Population | Overall Survival | 2 participants |