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

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00282282
• Collaborator: Brigham and Women's Hospital (Other)
• Enrollment: 31
• Location: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease; GVHD	Drug: tacrolimus; Drug: sirolimus; Drug: fludarabine; Drug: busulfex	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tacrolimus and Sirolimus as Graft Versus Host Disease Prophylaxis After Allogeneic Non-myeloablative Peripheral Blood Stem Cell Transplantation
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Vincent Ho, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vincent T. Ho, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00282282
• Other Study ID Numbers: 05-362
• First Posted: Jan 26, 2006
• Last Update Posted: May 12, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Vincent T. Ho, MD, Principal Investigator, Dana-Farber Cancer Institute: non-myeloablative peripheral blood stem cell; PBSCT; tacrolimus; sirolimus
• Additional relevant MeSH terms: Graft vs Host Disease; Sirolimus; Fludarabine; Busulfan; Tacrolimus

Study Results

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.

Arm/Group Title	Tacrolimus and Sirolimus
Arm/Group Description	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.
Period Title: Overall Study
STARTED	29
COMPLETED	29
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tacrolimus and Sirolimus
Arm/Group Description	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.
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	29 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	12 41.4%
Male	17 58.6%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Grade II-IV Acute GVHD (aGVHD) Developing by Day 100 Following Non-myeloablative PBSC Transplantation Using Tacrolimus and Sirolimus.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tacrolimus and Sirolimus
Arm/Group Description
Measure Participants	29
Number [participants]	5 17.2%

2. Secondary Outcome

Title	Percentage of Participants With ≥90 Percent Donor-derived Hematopoeisis Around 100 Days Post Transplantation
Description	The percentage of participants with ≥90 percent donor-derived hematopoeisis was assessed around day +100 using peripheral blood chimerism.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus and Sirolimus
Arm/Group Description
Measure Participants	27
Number [percentage of participants]	78 269%

3. Secondary Outcome

Title	Disease Response.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus and Sirolimus GVHD Prophylaxis
Arm/Group Description
Measure Participants	29
Number (95% Confidence Interval) [percentage of participants]	48 165.5%

Adverse Events

Time Frame	Participants were followed for approximately 2 years post-transplant
Arm/Group Title	Tacrolimus and Sirolimus
Arm/Group Description	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.
All Cause Mortality
	Tacrolimus and Sirolimus
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tacrolimus and Sirolimus
	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)
Blood and lymphatic system disorders
Thrombotic Microangiopathy	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Tacrolimus and Sirolimus
	Affected / at Risk (%)	# Events
Total	0/29 (0%)

Limitations/Caveats

This study is a single-institution study, and as such the data are limited by the small study population.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.