Trial Outcomes & Findings for In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis (NCT NCT01927120)

NCT ID: NCT01927120

Last Updated: 2017-07-02

Results Overview

Percentage of Treg among blood CD4+ T cells at day 30 after hematopoietic cell transplantation (HCT), to compare to SIR/TAC alone data from a previous trial (median of 16%). The study was designed to capture an increase in regulatory T cells from a median of 16.0% at day +30.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

30 days post HCT

Results posted on

2017-07-02

Participant Flow

Participants were enrolled at Moffitt Cancer Center, April 2014 through December 2015.

Participant milestones

Participant milestones
Measure	GVHD Regimen Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Overall Study STARTED	20
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age, Continuous	49 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days post HCT

Population: All participants.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT	23.8 percentage of CD4+Tregs Interval 12.8 to 39.3

SECONDARY outcome

Timeframe: 365 days post HCT

Population: All participants.

Overall survival will be defined as the time from transplant date to death from any cause.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Overall Survival at Day +365	77.1 percentage of participants Interval 49.3 to 90.7

SECONDARY outcome

Timeframe: 1 year post HCT

Population: All participants.

Incidence of primary disease relapse per standard definitions.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Cumulative Incidence of Relapse	35.2 percentage of participants Interval 9.2 to 63.3

SECONDARY outcome

Timeframe: 100 days post HCT

Population: All participants.

Acute GVHD will be graded per the 1995 consensus guidelines.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Cumulative Incidence of Grade II-IV Acute GVHD by Day +100	40 percentage of participants Interval 15.8 to 63.4

SECONDARY outcome

Timeframe: 365 days post HCT

Population: All participants.

Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Cumulative Incidence of Chronic GVHD by Day +365	61.5 percentage of participants Interval 36.1 to 79.3

SECONDARY outcome

Timeframe: 365 days post HCT

Population: All participants.

Incidence of Non-relapse death/Transplant-related mortality. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Incidence of Non-relapse Death	5.0 percentage of participants Interval 0.0 to 65.6

SECONDARY outcome

Timeframe: Up to days 130 post HCT

Population: All participants.

Grade 3-5 unexpected or serious adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.03) were captured up to day +130 or 30 days after the last dose of IL-2. Events listed, with causality in relation to study treatment noted.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Incidence of Unexpected or Serious Adverse Events (AEs) VOD, possibly related	2 adverse events
Incidence of Unexpected or Serious Adverse Events (AEs) Portal vein thrombosis, possibly related	1 adverse events
Incidence of Unexpected or Serious Adverse Events (AEs) Sepsis, unlikely to be related	1 adverse events
Incidence of Unexpected or Serious Adverse Events (AEs) GI bleed, unrelated	1 adverse events
Incidence of Unexpected or Serious Adverse Events (AEs) Acute kidney injury, unrelated	3 adverse events
Incidence of Unexpected or Serious Adverse Events (AEs) Kidney stone, unrelated	1 adverse events
Incidence of Unexpected or Serious Adverse Events (AEs) Intracranial hemorrhage, unrelated	1 adverse events

SECONDARY outcome

Timeframe: 90 days post HCT

Population: All participants.

The proportion of Tregs to non-Treg CD4+ cells to be assessed at day +90. Natural Killer Cells (NKs): Median K/uL NK cells.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Proportion of Treg Among Blood CD4+ T Cells at Day +90 After HCT	0.212 K/uL NK cells Interval 0.079 to 0.605

SECONDARY outcome

Timeframe: 30 days post HCT

Population: All participants.

Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +30.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30 pSTAT3	34.1 percentage in total CD4s Interval 10.4 to 99.7
STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30 pSTAT5	97.1 percentage in total CD4s Interval 44.0 to 99.9
STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30 pS6	19.3 percentage in total CD4s Interval 13.8 to 41.1

SECONDARY outcome

Timeframe: 90 days post HCT

Population: All participants.

Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +90.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=20 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 pSTAT3	20.2 percentage in total CD4s Interval 2.56 to 61.8
STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 pSTAT5	78.6 percentage in total CD4s Interval 33.6 to 100.0
STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 pS6	16.3 percentage in total CD4s Interval 0.91 to 26.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 30 days post HCT

Population: All evaluable participants at day +30.

Percent of Treg suppression at day +30. Investigators had also planned to test Treg function at day +90, if sufficient Tregs had been available for analysis.

Outcome measures

Outcome measures
Measure	GVHD Regimen n=3 Participants Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Function of Blood Treg After Allogeneic HSCT	61.0 percentage of suppression Standard Deviation 11.15

OTHER_PRE_SPECIFIED outcome

Timeframe: 365 days post HCT

Population: Lab test results to be compared to compiled data at a later date.

Investigators planned to monitor natural killer cell (NK) reconstitution. Standard immune deficiency flow cytometry panels (IDP) was to be drawn on days +90, +180, and +365 to evaluate NK reconstitution. Results of standard lab tests to be compared to compiled data at a later date

Outcome measures

Outcome data not reported

Adverse Events

GVHD Regimen

Serious events: 11 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GVHD Regimen n=20 participants at risk Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Blood and lymphatic system disorders Anemia	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Cardiac disorders Atrial fibrillation	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Cardiac disorders Sinus tachycardia	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Gastrointestinal disorders Abdominal pain	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Gastrointestinal disorders Colonic hemorrhage	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Gastrointestinal disorders Nausea	10.0% 2/20 • Number of events 2 • 2 years, 6 months
Gastrointestinal disorders Vomiting	10.0% 2/20 • Number of events 2 • 2 years, 6 months
General disorders Fever	15.0% 3/20 • Number of events 3 • 2 years, 6 months
General disorders Pain	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Hepatobiliary disorders Hepatobiliary disorders - Other, VOD	10.0% 2/20 • Number of events 2 • 2 years, 6 months
Hepatobiliary disorders Portal vein thrombosis	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Infections and infestations Infections and infestations - Other, pneumonia	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Infections and infestations Infections and infestations - Other, staphylococcus epidermis bacteremia	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Infections and infestations Sepsis	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Nervous system disorders Intracranial hemorrhage	5.0% 1/20 • Number of events 2 • 2 years, 6 months
Renal and urinary disorders Acute kidney injury	10.0% 2/20 • Number of events 2 • 2 years, 6 months
Renal and urinary disorders Cystitis non-infective	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Renal and urinary disorders Renal and urinary disorders - Other, adenovirus cystitis	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Renal and urinary disorders Renal and urinary disorders - Other, kidney stones	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Vascular disorders Hypotension	5.0% 1/20 • Number of events 1 • 2 years, 6 months

Other adverse events

Other adverse events
Measure	GVHD Regimen n=20 participants at risk Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Gastrointestinal disorders Ileus	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Hepatobiliary disorders Hepatobiliary disorders - Other, portal vein thrombosis	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Investigations Alanine aminotransferase increased	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Investigations Aspartate aminotransferase increased	5.0% 1/20 • Number of events 1 • 2 years, 6 months
Vascular disorders Hypertension	5.0% 1/20 • Number of events 1 • 2 years, 6 months

Additional Information

Dr. Brian Betts

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-5410

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place