Tacrolimus and Sirolimus as Prophylaxis After Allogenic Non-myeloablative Peripheral Blood Stem Cell Transplantation

Graft Versus Host Disease Clinical Trial

Official title:

Tacrolimus and Sirolimus as Graft Versus Host Disease Prophylaxis After Allogeneic Non-myeloablative Peripheral Blood Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282282
• Other study ID #: 05-362
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2006
• Last updated: April 29, 2014
• Start date: January 2006
• Est. completion date: July 2009

Study information

• Verified date: March 2014
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: July 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• GVHD

Intervention

Drug:
• tacrolimus
Given orally just prior to and following stem cell transplant
• sirolimus
Given orally just prior to and following stem cell transplant
• fludarabine
Given once daily over 30 minutes for 4 days
• busulfex
Given intravenously over 3 hours for 4 days

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ho VT, Aldridge J, Kim HT, Cutler C, Koreth J, Armand P, Antin JH, Soiffer RJ, Alyea EP. Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and mini-methotrexate (Tac/Sir/MTX) as acute graft-versus-host disease prophylaxis afte — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	100 days	Yes
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.	100 days	No
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.	2 years	No