In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis
- Conditions
- Graft-Versus-Host-Disease
- Interventions
- Registration Number
- NCT01927120
- Brief Summary
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).
- Detailed Description
1) 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
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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.
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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.
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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.
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Performance status: Karnofsky Performance Status Score ≥ 80%
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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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GVHD Regimen IL-2 Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT). GVHD Regimen Sirolimus Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT). GVHD Regimen Tacrolimus Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
- Primary Outcome Measures
Name Time Method Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT 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 Outcome Measures
Name Time Method STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 90 days post HCT Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +90.
Overall Survival at Day +365 365 days post HCT Overall survival will be defined as the time from transplant date to death from any cause.
Cumulative Incidence of Relapse 1 year post HCT Incidence of primary disease relapse per standard definitions.
Cumulative Incidence of Grade II-IV Acute GVHD by Day +100 100 days post HCT Acute GVHD will be graded per the 1995 consensus guidelines.
Cumulative Incidence of Chronic GVHD by Day +365 365 days post HCT Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria.
Incidence of Non-relapse Death 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) 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 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 30 days post HCT Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +30.
Trial Locations
- Locations (1)
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States