RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells.
When the healthy stem cells from a donor are infused into the patient they may help the
patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Once the donated stem cells begin working, the patient's immune system may see the remaining
cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of
donor T cells may helps stop the patient's immune system from rejecting the donor's stem
PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in
treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood
stem cell transplant.
Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed
before Phase II portion of study.
- 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
- 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.
- 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
- MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body
irradiation) followed by HLA-identical sibling peripheral blood progenitor cells
- 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
- Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human
T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative
- Not pregnant or nursing