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

Phase 2CompletedNCT01927120

H. Lee Moffitt Cancer Center and Research Institute20 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Graft-Versus-Host-Disease

Interventions

IL-2DRUG

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).

TacrolimusDRUG

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

SirolimusDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Outcomes

Primary Outcomes

Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 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.

Time frame: 30 days post HCT

Secondary Outcomes

Overall Survival at Day +365

Overall survival will be defined as the time from transplant date to death from any cause.

Time frame: 365 days post HCT

Cumulative Incidence of Relapse

Incidence of primary disease relapse per standard definitions.

Time frame: 1 year post HCT

Cumulative Incidence of Grade II-IV Acute GVHD by Day +100

Acute GVHD will be graded per the 1995 consensus guidelines.

Time frame: 100 days post HCT

Cumulative Incidence of Chronic GVHD by Day +365

Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria.

Time frame: 365 days post HCT

Incidence of Non-relapse Death

Incidence of Non-relapse death/Transplant-related mortality. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation.

Time frame: 365 days post HCT

Incidence of Unexpected or Serious Adverse Events (AEs)

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.

Data from ClinicalTrials.gov

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