Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

OBJECTIVES:

Primary

- To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely
administered to patients undergoing HLA-identical sibling donor Peripheral Blood
Progenitor Cell (PBPC) transplantation.

- To determine whether CD4+ and CD25+ cells can be safely administered to patients with
high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC
transplantation.

Secondary

- To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD),
chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T
cells in these patients.

OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed
by a phase II study. All patients receive myeloablative preparative therapy and GVHD
prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10.

- First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive
unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over
15-60 minutes at the assigned dose on day -2.

- Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC
transplantation IV on day 0.

Patients undergo blood sample collection prior to commencement of preparative therapy and
then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for
immune reconstitution by immunophenotyping and functional analyses.

After completion of study therapy, patients are followed for up to 1 year.

Inclusion Criteria:

- Diagnosis of a high-risk hematologic malignancy, including any of the following:

- Acute lymphocytic leukemia

- Acute myelocytic leukemia

- Chronic myelogenous leukemia

- Myelodysplastic syndrome

- Non-Hodgkin lymphoma

- Multiple myeloma

- Meet eligibility criteria and co-enrolled in one of the following University of
Minnesota protocols:

- MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body
irradiation) followed by HLA-identical sibling peripheral blood progenitor cells
(PBPC) transplantation

- MT2001-10 consisting of nonmyeloablative prep (cyclophosphamide, fludarabine and
total body irradiation) followed by HLA-identical sibling PBPC transplantation

- Voluntarily written informed consent

- Must have an HLA-identical sibling donor available, meeting the following criteria:

- 12 to 75 years of age, >40 kg body weight and in good health

- Matched to recipient for HLA-A, B,DRB1 identical sibling match to recipient

- Must be able and willing to have a separate apheresis collection performed on day
-21 for the purposes of this study (in addition to the apheresis required for the
transplant protocol)

- Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human
T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative

Exclusion Criteria:

- Not pregnant or nursing