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

Graft-Versus-Host-Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01927120
• Other study ID #: MCC-17578
• Secondary ID: NCI-2014-00755
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 16, 2013
• Last updated: March 30, 2017
• Start date: March 25, 2014
• Est. completion date: January 2018

Study information

• Verified date: March 2017
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: January 2018
• Est. primary completion date: August 25, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Graft vs Host Disease
• Graft-Versus-Host-Disease

Intervention

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

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In Vivo Treg Expansion	Proportion of Treg among blood CD4+ T cells at day 30 after hematopoietic cell transplantation (HCT)	30 days post transplant

External Links

•   H. Lee Moffitt Cancer Center & Research Institute