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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Terminated

CT.gov ID

NCT00725062

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 cells.

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes	Biological: CD4+CD25+ regulatory T cells Procedure: allogeneic hematopoietic stem cell transplantation	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients Receiving CD4+/CD25+ cells CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)	Biological: CD4+CD25+ regulatory T cells Cohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg Procedure: allogeneic hematopoietic stem cell transplantation Occurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation Other Names: peripheral blood progenitor cell (PBPC) transplantation

Arm

Intervention/Treatment

Experimental: Patients Receiving CD4+/CD25+ cells

CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)

Biological: CD4+CD25+ regulatory T cells

Cohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg

Procedure: allogeneic hematopoietic stem cell transplantation

Occurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation

Other Names:

peripheral blood progenitor cell (PBPC) transplantation

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of CD4+CD25+ cells/kg (phase I) [Day 0 (48 hours post infusion)]
Incidence of grade 3-5 infusional toxicity (phase II) [Day 0 (48 hours post infusion)]

Secondary Outcome Measures

Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD) [Day 100 Post Infusion]
Incidence of chronic graft-versus-host disease (GVHD) [Month 6 Post Infusion]
Incidence of Relapse [Month 6 Post Infusion]
Overall Survival [Day 100 and 1 Year Post Infusion]
Disease-free survival [Day 100 and 1 Year Post Infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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