Graft Versus Host Disease, GVHD
Conditions
Keywords
non-myeloablative peripheral blood stem cell, PBSCT, tacrolimus, sirolimus
Brief summary
The purpose of this study is to extend the use of Tacrolimus and Sirolimus to determine how effective it is in preventing graft versus host disease (GVHD)in patients that have received non-myeloablative peripheral blood stem cell transplantation.
Detailed description
* After the screening procedures confirm that the patient is eligible to participate in the research study, they will be admitted to the hospital to receive chemotherapy and stem cell transplantation (SCT). The duration of the hospitalization for the procedure is approximately 8 days. * Patients will receive fludarabine once daily over 30 minutes intravenously for 4 days and busulfex once daily over 3 hours intravenously each day for the same 4 days. * Just prior to the transplant and following the transplant the patient will receive sirolimus and tacrolimus to help prevent Graft versus Host Disease (GvHD). Both medications are taken orally. * Patients will also take medications to help prevent possible infections (e.g. acyclovir). Filgrastim, a white blood cell growth factor, will be given daily in an injection under the skin, starting the day after the stem cell transplant and until the patients blood counts have recovered. * After the stem cell infusion, the patient will be examined and have blood tests weekly for 1 month. At about the 1-month visit, a bone marrow biopsy and/or blood tests will be performed to determine the percentage of donor's cells in the blood or bone marrow. These tests will be repeated at 3-4 months after transplant. * At 3-4 months after the transplant, patients will also have tests to reassess the response of your disease to transplant. This may involve a bone marrow biopsy, blood tests, and/or radiology studies depending upon the type of cancer. * Follow-up will continue for the remainder of the patients life.
Interventions
DRUGtacrolimus
Given orally just prior to and following stem cell transplant
DRUGsirolimus
Given orally just prior to and following stem cell transplant
DRUGfludarabine
Given once daily over 30 minutes for 4 days
DRUGbusulfex
Given intravenously over 3 hours for 4 days
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
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
* Patients with hematologic malignancies who are at a high risk of complications after conventional transplantation * Availability of a related donor who is identical at 6 HLA loci * Greater than 18 years of age * Performance status 0-2 * Life expectancy of \> 100 days
Exclusion criteria
* Pregnancy * Evidence of HIV infection * Heart failure uncontrolled medication * Total bilirubin \> 2.0mg/dl that is due to hepatocellular dysfunction * AST \>90 * Serum Creatinine \>2.0 * Cholesterol \> 300mg/dl while adequately treated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade II-IV Acute GVHD (aGVHD) Developing by Day 100 Following Non-myeloablative PBSC Transplantation Using Tacrolimus and Sirolimus. | 100 days | All participants received tacrolimus and sirolimus in this one arm study. There were no participants considered unevaluable for this measure (deceased prior to day 100). The total number of people who developed grade II-IV aGVHD before day 100 are reported here. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response. | 2 years | Disease response was assessed as 2 year progression-free survival. The median follow-up time was 1.84 years. The percentage of participants with who reached this timepoint with no disease progression are reported. |
| Percentage of Participants With ≥90 Percent Donor-derived Hematopoeisis Around 100 Days Post Transplantation | 100 days | The percentage of participants with ≥90 percent donor-derived hematopoeisis was assessed around day +100 using peripheral blood chimerism. |
Countries
United States
Participant flow
Recruitment details
Patients with hematologic malignancies who were at high risk of complications after conventional transplantation, with 6/6 HLA matched-related donors were approached with information about participating in the study. Participants were approached at either inpatient or outpatient clinics by physicians between 2006 and 2007.
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus and Sirolimus Participants received a tacrolimus and sirolimus graft-versus-host disease (GVHD) prophylaxis regimen. Tacrolimus was given 0.05 mg/kg/day (in 2 daily divided doses) orally starting 3 days before bone marrow transplant with a target serum concentration of 5-10ng/mL. Sirolimus was administered with a 12mg oral loading dose 3 days prior to transplantwith a target serum concentration of 3-12ng/mL. Tapering of tacrolimus and sirolimus doses was encouraged starting 64 days after transplant with a goal of discontinuing immunosuppression therapy approximately 6 months after transplant if there were no signs of GVHD. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Tacrolimus and Sirolimus |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 53 years |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 1 / 29 |
Outcome results
Primary
Incidence of Grade II-IV Acute GVHD (aGVHD) Developing by Day 100 Following Non-myeloablative PBSC Transplantation Using Tacrolimus and Sirolimus.
All participants received tacrolimus and sirolimus in this one arm study. There were no participants considered unevaluable for this measure (deceased prior to day 100). The total number of people who developed grade II-IV aGVHD before day 100 are reported here.
Time frame: 100 days
Population: Participants who lived more than 30 days posttransplant were considered evaluable. Incidence of grade II-IV aGVHD was adjusted for participants who had aGVHD off-treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus and Sirolimus | Incidence of Grade II-IV Acute GVHD (aGVHD) Developing by Day 100 Following Non-myeloablative PBSC Transplantation Using Tacrolimus and Sirolimus. | 5 participants |
Secondary
Disease Response.
Disease response was assessed as 2 year progression-free survival. The median follow-up time was 1.84 years. The percentage of participants with who reached this timepoint with no disease progression are reported.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus and Sirolimus | Disease Response. | 48 percentage of participants |
Secondary
Percentage of Participants With ≥90 Percent Donor-derived Hematopoeisis Around 100 Days Post Transplantation
The percentage of participants with ≥90 percent donor-derived hematopoeisis was assessed around day +100 using peripheral blood chimerism.
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus and Sirolimus | Percentage of Participants With ≥90 Percent Donor-derived Hematopoeisis Around 100 Days Post Transplantation | 78 percentage of participants |