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Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation


Phase 1
18 Years
70 Years
Not Enrolling
Both
Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

Thank you

Trial Information

Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)

Outcome Time Frame:

Day 0 (48 hours post infusion)

Safety Issue:

Yes

Principal Investigator

Margaret L. MacMillan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2004LS034

NCT ID:

NCT00725062

Start Date:

June 2008

Completion Date:

April 2010

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • graft versus host disease
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • stage III adult Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • recurrent adult acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location
Masonic Cancer Center, University of Minnesota Minneapolis, Minnesota  55455