Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant

NCT01627275 | Completed Phase 1 DMC

• 1 other identifier: Pro00003975
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic stem cell transplantation offers the hope of cure for a wide variety of hematologic malignancies. Mature donor T-cells play a critical role in the success or failure of this procedure and a subset of donor T-cells mediate graft-versus-host disease while other subsets provide the foundation for immune recovery. The major challenge in allogeneic stem cell transplantation is determining how to maximally exploit the beneficial effects mediated by T-cells without causing GvHD. This challenge could be overcome by selectively depleting the population of donor T-cells responsible for eliciting the GvHD response. The study hypothesis is depletion of naïve T-cells from the donor lymphocyte inoculum will not cause GVHD while providing T-cells to affect both anti-infection and anti-tumor responses.

Conditions

Hematological Malignancies

Keywords

Naive T Cell Depletion; Donor Lymphocyte Infusion; Allogeneic Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• MTD of Naive TCD DLI

  To determine the maximum tolerated dose (MTD) of a Naive T cell depleted (TCD) donor lymphocyte infusion (DLI) post alemtuzumab-containing allogeneic transplant procedure from a HLA-identical family donor, or an 8/8 HLA-matched unrelated donor and derive a preliminary assessment of the efficacy of the naive T-cell depleted DLI.

  12 months

Secondary Outcomes (4)

• Immunological Recovery

  12 months

• Overall Incidence of Acute GVHD

  60 Days

• Overall Incidence of Opportunistic Infections

  60 Days

• Overall Incidence of Chronic GVHD

  12 months

Study Arms (1)

DLI from HLA-identical donor

EXPERIMENTAL

Naive T Cell Depleted Donor Lymphocyte Infusion from HLA matched family member donor or 8/8 HLA matched unrelated donor.

Biological: Naive T Cell Depleted Donor Lymphocyte Infusion

Interventions

Naive T Cell Depleted Donor Lymphocyte Infusion BIOLOGICAL

A single naive T-cell depleted donor lymphocyte infusion will be administered through a peripheral or central venous catheter greater than or equal to 60 days post allogeneic hematopoietic stem cell transplant.

Also known as: CD45RA+ T Cells

DLI from HLA-identical donor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have undergone an alemtuzumab or thymoglobulin-containing allogeneic transplant procedure from an HLA-identical family donor, or an 8/8 HLA-matched unrelated donor.
• At least 60 days from day of transplantation.
• Karnofsky performance status 50-100%.
• Donor myeloid engraftment (from peripheral blood or bone marrow) of at least 40% documented ≤ 60 days from protocol therapy.
• No active acute GvHD ≥ grade II.
• Prednisone (or equivalent corticosteroid) dose ≤ 20mg, daily mycophenolate mofetil dose ≤2000mg/d and cyclosporine/tacrolimus at ≤ therapeutic blood trough levels.
• No change in dosing of immunosuppressive agents 2 weeks before the naïve T-cell depleted donor lymphocyte infusion.
• A commitment not to electively taper for a minimum of 60 days, the immunosuppressive medications ongoing at time of naïve T-cell depleted donor lymphocyte infusion.
• No extensive chronic GvHD.
• Age ≥ 18 years of age.

You may not qualify if:

• Pregnant or lactating women.
• Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.

Sponsors & Collaborators

• Mitchell Horwitz, MD: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Mitchell Horwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 21, 2012
• First Posted: June 25, 2012
• Study Start: June 1, 2012
• Primary Completion: February 24, 2017
• Study Completion: August 3, 2017
• Last Updated: February 13, 2018

Record last verified: 2018-02

Locations

US (1)