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
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Malignancies focused on measuring CD25+, Tregs, DLI, Donor lymphocyte infusion
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
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
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
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
No
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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