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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01927120
Recruitment Status : Completed
First Posted : August 22, 2013
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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).

Condition or disease Intervention/treatment Phase
Graft-Versus-Host-Disease Drug: IL-2 Drug: Tacrolimus Drug: Sirolimus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: GVHD Regimen
Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Drug: IL-2
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)

Drug: Tacrolimus
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

Drug: Sirolimus
Orally on day -1. The dose for loading is 12 mg by mouth (PO)
Other Name: Rapamune

Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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:

    1. Left ventricular ejection fraction (LVEF) ≥ 45% by multi gated acquisition (MUGA) scan or ECHO
    2. 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
    3. Transaminases (AST, ALT) < 2 times upper limit of normal values
    4. 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01927120

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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
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Principal Investigator: Brian Betts, MD Moffitt Cancer Center
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT01927120    
Other Study ID Numbers: MCC-17578
NCI-2014-00755 ( Other Identifier: NCI CTRP )
First Posted: August 22, 2013    Key Record Dates
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017
Last Verified: March 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Hematopoietic Cell Transplant
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents