Infusion of Donor Lymphocytes Depleted of CD25+ Regulatory T-cells in Patients With Relapsed Hematologic Malignancies

September 28, 2016 updated by: John Koreth, MD, Dana-Farber Cancer Institute

Infusion of Donor Lymphocytes Depleted of CD25+ Regulatory T-cells in Patients With Relapsed Hematologic Malignancies After Matched Allogeneic Hematopoietic Stem Cell Transplantation

The purpose of this research study is to evaluate the safety and efficacy of cell depletion in a donor lymphocyte infusion (DLI) product with the use of the CliniMACS machine. Previously, patients with hematologic malignancies who have relapsed after transplant have been given infusions of donor white blood cells calsed donor lymphocyte infusion (DLI) as a way to boost their immune function and fight cancer. Information from other research studies suggests that lowering the number of a certain type of white blood cell called CD25+ Tregs in the DLI may allow for a greater effect. In this research study, we are looking for the appropriate dose of DLI depleted of the CD25+ Treg white blood cells that can be given safely.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • The original marrow/stem cell donor will undergo one or two white blood cell collection procedures called leukopheresis. The cells collected from the first leukopheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. If the number of cells collected at the first leukopheresis is not enough, the donor will have a second leukopheresis procedure.
  • Once enough lymphocytes are collected from the donor, the CliniMACS CD25 Reagent System device will reduce the number of CD25+ Tregs. The CD25+ depleted donor lymphocytes will then be infused to the participant intravenously. Participants will be observed for about one hour after the infusion.
  • One, two, four and eight weeks after the DLI, participants will return to the clinic for follow-up visits. At each visit a physical exam, questions about the participants general health, and blood tests will be performed.

Study Type

Interventional

Enrollment (Actual)

24

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
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with hematologic malignancies that have relapsed after HLA-A, -B, -C, and-DRBI matched allogeneic hematopoietic stem cell transplantation
  • At least 2 months following hematopoietic stem cell transplantation
  • Off any systemic immunosuppressive medication for treatment or prevention of GVHD, for a minimum of 2 weeks prior to study entry
  • Recipient with donor chimerism of 20% or greater within 6 weeks prior to DLI
  • Patient with less than 50% bone marrow involvement (% cellularity) and less than 5cm lymph nodes, in the 6 weeks prior to DLI
  • 18 years of age or older
  • ECOG Performance Status score 0-2
  • Prior stem cell donor is medically fit to undergo leukapheresis procedure

Exclusion Criteria:

  • Relapsed CML in chronic phase
  • Prior donor lymphocyte infusion or other immunotherapy treatment within 8 weeks prior to enrollment
  • Chemotherapy within 4 weeks prior to enrollment
  • Clinically significant and active autoimmune disease in donor or patient. This is defined as autoimmune disease resulting in organ dysfunction and/or requiring systemic therapy
  • Evidence of active acute or chronic GVHD
  • Uncontrolled infection

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CD25+ Treg depleted DLI dose schema

Patients will receive a defined dose of CD25+ Treg depleted DLI. 5 patients will be enrolled, initially at dose level B, and subsequent cohorts will be dose adjusted per the CD3+ dose escalation/de-escalation schema:

  • Dose level -C: 3x10^7 (CD3+Dose (#cells/kg*))
  • Dose level -B: 1x10^7 (CD3+Dose (#cells/kg*))
  • Dose level -A: 1x10^6 (CD3+Dose (#cells/kg*)) *Recipient's body weight in Kg
Device: CliniMACS CD25 Reagent Device
Used to engineer CD25+ depleted donor lymphocytes which will be infused intravenously over 5-10 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol
Time Frame: 3 years
3 years
To determine the safety of CD25+ Treg depleted DLI in this patient population.
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess clinical response after infusions of CD25+ Treg depleted donor lymphocytes
Time Frame: 3 years
3 years
To assess the immunologic impact of infusions of CD25+ Treg depleted donor lymphocytes
Time Frame: 3 years
3 years

Collaborators and Investigators

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

Sponsor

Dana-Farber Cancer Institute

Collaborators

Miltenyi Biomedicine GmbH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

December 1, 2007

Primary Completion (ACTUAL)

January 1, 2013

Study Completion (ACTUAL)

January 1, 2013

Study Registration Dates

First Submitted

May 8, 2008

First Submitted That Met QC Criteria

May 8, 2008

First Posted (ESTIMATE)

May 12, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

September 29, 2016

Last Update Submitted That Met QC Criteria

September 28, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-193

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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