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

NCT ID: NCT01927120

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-25
• Study Completion Date: 2017-03-09

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.

Conditions

Graft-Versus-Host-Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

GVHD Regimen

Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).

Group Type: EXPERIMENTAL

IL-2

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: 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

Intervention Type: DRUG

Sirolimus

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

Intervention Type: DRUG

Other Intervention Names

Proleukin®; (aldesleukin); Rapamune

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Betts, MD

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

References

Betts BC, Pidala J, Kim J, Mishra A, Nishihori T, Perez L, Ochoa-Bayona JL, Khimani F, Walton K, Bookout R, Nieder M, Khaira DK, Davila M, Alsina M, Field T, Ayala E, Locke FL, Riches M, Kharfan-Dabaja M, Fernandez H, Anasetti C. IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation. Haematologica. 2017 May;102(5):948-957. doi: 10.3324/haematol.2016.153072. Epub 2017 Jan 19.

Reference Type: DERIVED

PMID: 28104702 (View on PubMed)

Related Links

http://www.moffitt.org

H. Lee Moffitt Cancer Center \& Research Institute

http://www.haematologica.org/content/early/2017/01/19/haematol.2016.153072.long

IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation

Other Identifiers

NCI-2014-00755

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-17578

Identifier Type: -

Identifier Source: org_study_id