Trial Outcomes & Findings for Graft-Versus-Host Disease (GVHD) Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation (NCT NCT00803010)

Results Overview

Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme. Acute GVHD classified as the following: 1. classic acute GVHD - onset within 100 days after transplant 2. persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100 3. recurrent - acute GVHD recurrent after prior episode of acute GVHD 4. late acute GVHD - syndrome consistent with acute GVHD, without features of chronic GVHD, with onset occurring beyond 100 days

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

74 participants

Primary outcome timeframe

100 Days Post Transplant

Results posted on

2015-07-31

Participant Flow

Patients recruited between 09/10/2008 through 05/13/2011 from the Blood and Marrow Transplant Program patient population.

Participant milestones

Participant milestones
Measure	1 Tacrolimus / Rapamycin Tacrolimus / Rapamycin Tacrolimus and Rapamycin (Sirolimus): Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.	2 Tacrolimus / Methotrexate Tacrolimus / Methotrexate Tacrolimus and Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m\^2, and a dose of 10 mg/m\^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.
Overall Study STARTED	37	37
Overall Study COMPLETED	37	37
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Graft-Versus-Host Disease (GVHD) Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tacrolimus / Rapamycin n=37 Participants Tacrolimus / Rapamycin Tacrolimus / Rapamycin: Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.	Tacrolimus / Methotrexate n=37 Participants Tacrolimus / Methotrexate Tacrolimus / Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m\^2, and a dose of 10 mg/m\^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.	Total n=74 Participants Total of all reporting groups
Age, Continuous	49 years n=5 Participants	48 years n=7 Participants	49 years n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	23 Participants n=7 Participants	51 Participants n=5 Participants
Region of Enrollment United States	37 participants n=5 Participants	37 participants n=7 Participants	74 participants n=5 Participants

PRIMARY outcome

Timeframe: 100 Days Post Transplant

Population: All participants who received treatment

Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme. Acute GVHD classified as the following: 1. classic acute GVHD - onset within 100 days after transplant 2. persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100 3. recurrent - acute GVHD recurrent after prior episode of acute GVHD 4. late acute GVHD - syndrome consistent with acute GVHD, without features of chronic GVHD, with onset occurring beyond 100 days

Outcome measures

Outcome measures
Measure	1 Tacrolimus / Rapamycin n=37 Participants Tacrolimus / Rapamycin Tacrolimus and Rapamycin (Sirolimus): Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.	2 Tacrolimus / Methotrexate n=37 Participants Tacrolimus / Methotrexate Tacrolimus and Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m\^2, and a dose of 10 mg/m\^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.
Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant	43 percentage of participants Interval 27.0 to 59.0	89 percentage of participants Interval 72.0 to 96.0

SECONDARY outcome

Timeframe: 30 days and 90 days

Absolute numbers of Treg at designated time points according to study arm. MTX = methotrexate/tacrolimus-treated patients; SIR = sirolimus/tacrolimus-treated patients; Treg absolute number units = number of cells/microL. A two-sided Wilcoxon's rank-sum test was employed to test differences in percent Treg (% Treg/total CD4+ cells).

Outcome measures

Outcome measures
Measure	1 Tacrolimus / Rapamycin n=37 Participants Tacrolimus / Rapamycin Tacrolimus and Rapamycin (Sirolimus): Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.	2 Tacrolimus / Methotrexate n=37 Participants Tacrolimus / Methotrexate Tacrolimus and Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m\^2, and a dose of 10 mg/m\^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.
Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) 30 Day Measure	16.27 Cells/MicroL Interval 12.49 to 17.89	9.87 Cells/MicroL Interval 8.59 to 13.47
Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) 90 Day Measure	14.6 Cells/MicroL Interval 10.76 to 18.1	9.67 Cells/MicroL Interval 7.48 to 11.56

SECONDARY outcome

Timeframe: 2 years

Population: All participants who received treatment

Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .

Outcome measures

Outcome measures
Measure	1 Tacrolimus / Rapamycin n=37 Participants Tacrolimus / Rapamycin Tacrolimus and Rapamycin (Sirolimus): Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.	2 Tacrolimus / Methotrexate n=37 Participants Tacrolimus / Methotrexate Tacrolimus and Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m\^2, and a dose of 10 mg/m\^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.
2 Year Post Transplant Overall Survival (OS) Rate	61 percentage of participants Interval 41.0 to 77.0	69 percentage of participants Interval 48.0 to 83.0

Adverse Events

Tacrolimus / Rapamycin

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Tacrolimus / Methotrexate

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tacrolimus / Rapamycin n=37 participants at risk Tacrolimus / Rapamycin Tacrolimus / Rapamycin: Tacrolimus - 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. Rapamycin - initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.	Tacrolimus / Methotrexate n=37 participants at risk Tacrolimus / Methotrexate Tacrolimus / Methotrexate: Tacrolimus administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 Methotrexate: administered on day 1 at dose of 15 mg/m\^2, and a dose of 10 mg/m\^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.
Cardiac disorders Cardiac General - Pericardial effusion	2.7% 1/37 • Number of events 1 • Up to 5 years	0.00% 0/37 • Up to 5 years
Gastrointestinal disorders Hemorrhage, GI-Lower GI NOS	2.7% 1/37 • Number of events 1 • Up to 5 years	0.00% 0/37 • Up to 5 years
Hepatobiliary disorders Hepatobiliary/Pancreas - Abdominal pain secondary to acute cholecystitis	0.00% 0/37 • Up to 5 years	2.7% 1/37 • Number of events 1 • Up to 5 years
Renal and urinary disorders Renal / Genitourinary - Obstruction, GU Bladder	0.00% 0/37 • Up to 5 years	2.7% 1/37 • Number of events 1 • Up to 5 years
Renal and urinary disorders Renal / Genitourinary - Renal Failure	2.7% 1/37 • Number of events 1 • Up to 5 years	0.00% 0/37 • Up to 5 years

Other adverse events

Adverse event data not reported

Additional Information

Dr. Joseph Pidala

H. Lee Moffitt Cancer Center

Phone: 813-745-4673

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place