Clinical trial NCT00675831: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematologic Malignancies
Keywords: CD25+
Tregs
DLI
Donor lymphocyte infusion
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Miltenyi Biomedicine GmbH
First posted: 2008-05-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol
timeFrame: 3 years
measure: To determine the safety of CD25+ Treg depleted DLI in this patient population.
timeFrame: 3 years
Secondary outcomes:
measure: To assess clinical response after infusions of CD25+ Treg depleted donor lymphocytes
timeFrame: 3 years
measure: To assess the immunologic impact of infusions of CD25+ Treg depleted donor lymphocytes
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: John Koreth, MBBS, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
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.