Trial Outcomes & Findings for Tacrolimus and Sirolimus as Prophylaxis After Allogenic Non-myeloablative Peripheral Blood Stem Cell Transplantation (NCT NCT00282282)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

100 days

Results posted on

2014-05-12

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	29
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tacrolimus and Sirolimus n=29 Participants 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.
Age, Categorical Between 18 and 65 years	29 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	53 years n=93 Participants
Sex: Female, Male Female	12 Participants n=93 Participants
Sex: Female, Male Male	17 Participants n=93 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants
Region of Enrollment United States	29 participants n=93 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tacrolimus and Sirolimus n=29 Participants
Incidence of Grade II-IV Acute GVHD (aGVHD) Developing by Day 100 Following Non-myeloablative PBSC Transplantation Using Tacrolimus and Sirolimus.	5 participants

SECONDARY outcome

Timeframe: 100 days

The percentage of participants with ≥90 percent donor-derived hematopoeisis was assessed around day +100 using peripheral blood chimerism.

Outcome measures

Outcome measures
Measure	Tacrolimus and Sirolimus n=27 Participants
Percentage of Participants With ≥90 Percent Donor-derived Hematopoeisis Around 100 Days Post Transplantation	78 percentage of participants Interval 11.0 to 100.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tacrolimus and Sirolimus n=29 Participants
Disease Response.	48 percentage of participants Interval 29.0 to 64.0

Adverse Events

Tacrolimus and Sirolimus

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tacrolimus and Sirolimus n=29 participants at risk 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.
Blood and lymphatic system disorders Thrombotic Microangiopathy	3.4% 1/29 • Participants were followed for approximately 2 years post-transplant

Other adverse events

Adverse event data not reported

Additional Information

Vincent T. Ho, MD Associate Professor of Medicine, Harvard Medical School

Dana-Farber Cancer Institute

Phone: (617) 632-5938

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place