In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis
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|ClinicalTrials.gov Identifier: NCT01927120|
Recruitment Status : Completed
First Posted : August 22, 2013
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Graft-Versus-Host-Disease||Drug: IL-2 Drug: Tacrolimus Drug: Sirolimus||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis With IL-2, Sirolimus, and Tacrolimus Following Allogeneic Hematopoietic Cell Transplantation|
|Actual Study Start Date :||March 25, 2014|
|Actual Primary Completion Date :||August 25, 2016|
|Actual Study Completion Date :||March 9, 2017|
Experimental: GVHD Regimen
Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
A subcutaneous injection will be administered 3 times a week (separated by at least 1 day between injections), from day 0 to +90 (+/- 7 days).
Will be administered at 0.01 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3
Orally on day -1. The dose for loading is 12 mg by mouth (PO)
Other Name: Rapamune
- Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT [ Time Frame: 30 days post HCT ]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.
- Overall Survival at Day +365 [ Time Frame: 365 days post HCT ]Overall survival will be defined as the time from transplant date to death from any cause.
- Cumulative Incidence of Relapse [ Time Frame: 1 year post HCT ]Incidence of primary disease relapse per standard definitions.
- Cumulative Incidence of Grade II-IV Acute GVHD by Day +100 [ Time Frame: 100 days post HCT ]Acute GVHD will be graded per the 1995 consensus guidelines.
- Cumulative Incidence of Chronic GVHD by Day +365 [ Time Frame: 365 days post HCT ]Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria.
- Incidence of Non-relapse Death [ Time Frame: 365 days post HCT ]Incidence of Non-relapse death/Transplant-related mortality. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation.
- Incidence of Unexpected or Serious Adverse Events (AEs) [ Time Frame: Up to days 130 post HCT ]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.
- Proportion of Treg Among Blood CD4+ T Cells at Day +90 After HCT [ Time Frame: 90 days post HCT ]The proportion of Tregs to non-Treg CD4+ cells to be assessed at day +90. Natural Killer Cells (NKs): Median K/uL NK cells.
- STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30 [ Time Frame: 30 days post HCT ]Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +30.
- STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 [ Time Frame: 90 days post HCT ]Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +90.
- Function of Blood Treg After Allogeneic HSCT [ Time Frame: 30 days post HCT ]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.
- Rate of Natural Killer Cell (NK) Reconstitution [ Time Frame: 365 days post HCT ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01927120
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Brian Betts, MD||Moffitt Cancer Center|