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

Phase 1

Terminated

• Conditions: Multiple Myeloma and Plasma Cell Neoplasm; Leukemia; Lymphoma; Myelodysplastic Syndromes; Graft Versus Host Disease
• Interventions: Biological: CD4+CD25+ regulatory T cells; Procedure: allogeneic hematopoietic stem cell transplantation

• Registration Number: NCT00725062
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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.

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 Timeline

• Study Start: 2008-06
• Study First Submitted: 2008-07-29
• Study First Submitted QC: 2008-07-29
• Study First Posted: 2008-07-30
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-27
• Last Update Posted: 2017-11-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients Receiving CD4+/CD25+ cells	CD4+CD25+ regulatory T cells	CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)
Patients Receiving CD4+/CD25+ cells	allogeneic hematopoietic stem cell transplantation	CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Incidence of Relapse	Month 6 Post Infusion
Disease-free survival	Day 100 and 1 Year Post Infusion
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
Overall Survival	Day 100 and 1 Year Post Infusion

Trial Locations

Locations (1)

Masonic Cancer Center, University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States