In Vivo Treg Expansion and Graft-versus-Host Disease Prophylaxis
This trial is active, not recruiting.
|Treatments||il-2, tacrolimus, sirolimus|
|Sponsor||H. Lee Moffitt Cancer Center and Research Institute|
|Start date||March 2014|
|End date||October 2017|
|Trial size||22 participants|
|Trial identifier||NCT01927120, MCC-17578, NCI-2014-00755|
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).
|Endpoint classification||efficacy study|
|Intervention model||single group assignment|
In Vivo Treg Expansion
time frame: 30 days post transplant
Male or female participants at least 18 years old.
- 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.
- 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
|Official title||In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis With IL-2, Sirolimus, and Tacrolimus Following Allogeneic Hematopoietic Cell Transplantation|
|Principal investigator||Brian Betts, MD|
|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.|
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