Skip to main content
OpenTrials
Completed

NCT Number: NCT01927120

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

IL-2 add-back post allogeneic hematopoietic stem cell transplant (HSCT), combined with Sirolimus (SIR), Tacrolimus (TAC) will optimize Treg reconstitution and prevent graft versus host disease (GVHD).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Graft-versus-host-disease Graft vs Host Disease Immune System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

About this study

  • Determine if a GVHD prophylaxis regimen of IL-2/SIR/TAC enhances in vivo Treg differentiation and growth; 2) Study the safety and effects of IL-2/SIR/TAC on the incidence of acute and chronic GVHD; 3) Evaluate the influence of dual IL-2 supplementation and mammalian target of rapamycin (mTOR) inhibition on T cell-specific signaling pathways and the polarization of emerging T helper cells.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients must have an available 8/8 human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell graft.
  • Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, or myeloproliferative neoplasms requiring a matched allogeneic HSCT.
  • Acute Leukemia (AML or ALL) must be in complete remission defined as: <5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow >20% cellular, and peripheral absolute neutrophil count >1000/µL (platelet recovery is not required).
  • Myelodysplasia (MDS) and chronic myeloid leukemia (CML): Must have <5% marrow blasts.
  • Myeloproliferative neoplasms (MPN): Must have <5% peripheral / marrow blasts.
  • Adequate vital organ function:
  • Left ventricular ejection fraction (LVEF) ≥ 45% by multi gated acquisition (MUGA) scan or ECHO
  • Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing lung capacity oxygenation (DLCO) ≥ 50% of predicted values on pulmonary function tests
  • Transaminases (AST, ALT) < 2 times upper limit of normal values
  • Creatinine clearance ≥ 50 cc/min.
  • Performance status: Karnofsky Performance Status Score ≥ 80%
  • Donor eligibility: Eligible donors will include healthy sibling, relative or unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high resolution typing.

Exclusion criteria

  • Active infection not controlled with appropriate antimicrobial therapy
  • History of HIV, hepatitis B, or hepatitis C infection
  • Anti-thymocyte globulin, alemtuzumab, bortezomib, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT.
  • Hypersensitivity to recombinant human IL-2
  • Chronic lymphocytic leukemia, Hodgkin lymphoma, and non-hodgkin lymphoma are excluded as these malignancies may express the IL-2 receptor and pose a potential growth signal to any present disease.
  • Sorror's co-morbidity factors with total score >4

Treatment and study plan

IL-2

Drug

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).

Other names: Proleukin®, (aldesleukin)

Tacrolimus

Drug

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

sirolimus

Drug

Orally on day -1. The dose for loading is 12 mg by mouth (PO)

Other names: Rapamune

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. Cumulative Incidence of Relapse

    Time frame: 1 year post HCT

    Incidence of primary disease relapse per standard definitions.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

Other outcomes

  1. 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.

  2. 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

Sponsors and collaborators

Lead sponsor

H. Lee Moffitt Cancer Center and Research Institute

Other

Registry information

Official study title

In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis With IL-2, Sirolimus, and Tacrolimus Following Allogeneic Hematopoietic Cell Transplantation

Important dates

Study start
2014
Primary completion
2016
Study completion
2017
First posted
Aug 22, 2013
Registry last updated
Jul 2, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.