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

November 27, 2017 updated by: Masonic Cancer Center, University of Minnesota

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Margaret L. MacMillan, MD, Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

July 29, 2008

First Submitted That Met QC Criteria

July 29, 2008

First Posted (Estimate)

July 30, 2008

Study Record Updates

Last Update Posted (Actual)

November 29, 2017

Last Update Submitted That Met QC Criteria

November 27, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2004LS034
  • MT2004-03 (Other Identifier: Blood and Marrow Transplantation Program)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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