Donor Regulatory T Cells in Treating Patients With Visceral Acute Graft-versus-Host Disease After Stem Cell Transplant

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of donor T regulatory (Treg) cell infusions in
subjects with visceral acute graft-versus-host disease (aGVHD) and incidence of dose
limiting toxicities (DLTs) graded according to the Common Terminology Criteria for Adverse
Events (CTCAE version 4 [v.4]) with a focus on infusion reactions within 24 hours,
respiratory distress within 72 hours of infusion and all-cause mortality within 28 days of
infusion.

SECONDARY OBJECTIVES:

I. Determine the quantitative blood Treg cell changes following the cell infusions.

II. Assess dosing requirements and treatment response rates to primary steroid, secondary
and tertiary immunosuppressive therapy.

III. Post-transplant day +100 and day +180 survival. IV. Post-transplant incidence of
chronic graft-versus-host disease (GVHD) at day +180.

OUTLINE: This is a dose-escalation study.

Patients receive donor regulatory T lymphocytes intravenously (IV) over 5 minutes or less on
day 0. Some patients receive a second infusion of frozen donor regulatory T lymphocytes 5-7
days after the initial infusion or 2 additional infusions separated by 5-7 days.

After completion of study treatment, patients are followed up weekly until day 28 and then
on days 100 and 180.

Inclusion Criteria:

- Visceral aGVHD defined as: at least stage III/IV acute liver or stage II/III
gastrointestinal (GI) GVHD by clinical criteria and/or GI and/or liver biopsy
confirmation showing no alternative explanation for symptoms of GVHD

- Ability to understand and willingness to sign a written informed consent form

- Must have a 7/8 or 8/8 or haploidentical related donor matched at the human leukocyte
antigen (HLA)-A, B, C, DRB1 who was evaluated and provided the donor transplant graft

- Myeloablative or non-myeloablative allogeneic hematopoietic cell transplantation

- Karnofsky performance status >= 50

- DONOR: Age >= 18 to =< 77 years old

- DONOR: Karnofsky performance status of >= 70% defined by institutional standards

- DONOR: Must be the same sibling donor from whom the recipient's blood and marrow
graft was collected for the original allogeneic transplant that is HLA 7/8 or 8/8 or
haploidentical matched at the HLA-A, B, C, and DRB1

- DONOR: Serologies for human immunodeficiency virus (HIV) antigen (Ag), HIV 1 and HIV
2 antibody (Ab), human T-cell lymphotropic virus (HTLV) 1 and HTLV 2 Ab, hepatitis B
surface antigen (sAg) or polymerase chain reaction (PCR)+, or hepatitis C Ab or PCR+,
syphilis (Treponema) screen and HIV 1 and hepatitis C by NAT (nucleic acid testing)
have been collected prior to apheresis

- DONOR: Female donors of child-bearing potential must have a negative serum or urine
beta-human chorionic gonadotropin (HCG) test within two weeks of apheresis

- DONOR: Capable of undergoing leukapheresis, have adequate venous access, and be
willing to undergo insertion of a central catheter should leukapheresis via
peripheral vein be inadequate

- DONOR: Donor selection will be in compliance with 21 Code of Federal Regulations
(CFR) 1271

Exclusion Criteria:

- Uncontrolled infections not responsive to antimicrobial therapy requiring intensive
critical care

- Progressive malignant disease, including post-transplant lymphoproliferative disease
unresponsive to therapy

- Cytomegalovirus colitis or enteritis as defined by cytomegalovirus (CMV) shell vial
or culture positivity from endoscopic biopsy the discretion of the treating physician
based upon PCR positivity, clinical presentation and histology

- Respiratory insufficiency with oxygen requirement > 4 L nasal cannula

- Multi-organ failure

- DONOR: Evidence of active infection or viral hepatitis

- DONOR: HIV positive

- DONOR: Pregnant donor

- DONOR: Factors which place the donor at increased risk for complications from
leukapheresis