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

Primary Purpose

Hematologic Malignancies

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CliniMACS CD25 Reagent Device

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring CD25+, Tregs, DLI, Donor lymphocyte infusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD25+ Treg depleted DLI dose schema

Arm Description

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

Outcomes

Primary Outcome Measures

To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol

To determine the safety of CD25+ Treg depleted DLI in this patient population.

Secondary Outcome Measures

To assess clinical response after infusions of CD25+ Treg depleted donor lymphocytes

To assess the immunologic impact of infusions of CD25+ Treg depleted donor lymphocytes

Full Information

NCT ID

NCT00675831

First Posted

May 8, 2008

Last Updated

September 28, 2016

Sponsor

Dana-Farber Cancer Institute

Collaborators

Miltenyi Biomedicine GmbH

1. Study Identification

Unique Protocol Identification Number

NCT00675831

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

December 2007 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Dana-Farber Cancer Institute

Collaborators

Miltenyi Biomedicine GmbH

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancies

Keywords

CD25+, Tregs, DLI, Donor lymphocyte infusion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CD25+ Treg depleted DLI dose schema

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

CliniMACS CD25 Reagent Device

Intervention Description

Used to engineer CD25+ depleted donor lymphocytes which will be infused intravenously over 5-10 minutes

Primary Outcome Measure Information:

Title

To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol

Time Frame

3 years

Title

To determine the safety of CD25+ Treg depleted DLI in this patient population.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

To assess clinical response after infusions of CD25+ Treg depleted donor lymphocytes

Time Frame

3 years

Title

To assess the immunologic impact of infusions of CD25+ Treg depleted donor lymphocytes

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Koreth, MBBS, DPhil

Organizational Affiliation

Dana-Farber Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27354021

Citation

Nikiforow S, Kim HT, Daley H, Reynolds C, Jones KT, Armand P, Ho VT, Alyea EP 3rd, Cutler CS, Ritz J, Antin JH, Soiffer RJ, Koreth J. A phase I study of CD25/regulatory T-cell-depleted donor lymphocyte infusion for relapse after allogeneic stem cell transplantation. Haematologica. 2016 Oct;101(10):1251-1259. doi: 10.3324/haematol.2015.141176. Epub 2016 Jun 27.

Results Reference

derived

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

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