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

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Completed; Phase 2

Conditions: Graft-Versus-Host-Disease

Treatments: Drug: Tacrolimus; Drug: IL-2; Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT01927120

MCC-17578

NCI-2014-00755 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

GVHD Regimen

Experimental group

Description:

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

Treatment:

Drug: Tacrolimus

Drug: Sirolimus

Drug: IL-2