Clinical trial NCT00476177: Donor Dendritic Cells And Donor Lymphocytes in Patients With Relapsed Hematologic Malignancies After Allogeneic Transplant
Official title: Infusion of Donor Dendritic Cells and Donor Lymphocytes in Patients With Relapsed Hematologic Malignancies After Allogenic Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematologic Malignancy
Keywords: DC
DLI
graft vs. host disease
GVHD
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Beth Israel Deaconess Medical Center
name: National Cancer Institute (NCI)
First posted: 2007-05-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the safety of adding donor dendritic cells to donor lymphocyte infusions, and to determine the type and severity of any side effects associated with this addition. Previously patients with hematologic malignancies who relapsed after transplant have been given infusions of donor white blood cells (donor lymphocyte infusion, DLI) as a way to boost their immune function and fight disease. Although DLI has led to cancer regression in some patients, the overall response rate using DLI alone is low, and unfortunately, rarely lasting. Researchers have discovered a new subset of blood cells, called dendritic cells (DC), which are crucial partners to lymphocytes in generating an immune response. We believe that the infusion of DC together with DLI may improve the ability of the donor lymphocytes to recognize and kill cancer cells.

Detailed description: * Since we are looking for the highest dose of donor dendritic cells that can be administered safely with DLI patients after allogeneic stem cell transplant, not everyone who participates in this study will be receiving the same number of dendritic cells.
* The study procedure can be divided into 3 phases: 1) Pre-infusion evaluation, 2) Cell collections and infusions, 3) Follow-up after infusions.
* Pre-infusion evaluation: Routine blood tests will be performed on both the participant and donor. The participant will undergo a bone marrow aspirate and biopsy if this has not been recently performed. During this time, additional standard blood tests and/or radiology tests may be done to fully determine the extent of the cancer.
* Cell Collections: About 2-3 weeks before the infusion date, the 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 a portion will be used to cultivate dendritic cells, and the remaining lymphocytes will be set aside for the DLI. If the number of cells collected at the first leukopheresis is insufficient, the donor will undergo a second leukopheresis procedure 7-10 days later.
* Infusions: We plan to administer the dendritic cells and donor lymphocytes separately in the outpatient clinic. The dendritic cells will be given first, followed by the DLI one to two days later.
* Follow-up after infusions: After completion of both the donor DC and DLI, participants will be followed closely for the development of side effects and response. They will be evaluated at least once a week, and routine blood tests and physical examination to assess for graft vs. host disease (GvHD) or other side effects will be performed. Additional blood tests will be done after 3, 6, and 10 weeks. At 10 weeks after the lymphocyte infusion, bone marrow aspirate and biopsy will be performed to assess the disease as well as the percentage of bone marrow cells that are derived from the donor. Additional restaging studies will also be performed at 10 weeks.

Eligibility criteria: Inclusion Criteria:

* Patients with hematologic malignancies who have relapsed after related or unrelated donor hematopoietic stem cell transplantation (e.g. CML, AML, ALL, MDS, NHL, HD, CLL, MM)
* At least two months following hematopoietic stem cell transplantation
* Patients off any systemic immunosuppressive medication for treatment or prevention of GVHD for minimum of 2 weeks prior to initiation of therapy
* 18 years of age or older
* ECOG performance status 0-2
* Donor medically fit to undergo leukapheresis procedure

Exclusion Criteria:

* Relapsed CML in chronic phase
* Prior donor lymphocyte infusion or other immunotherapy treatment within 8 weeks of enrollment
* Clinically significant and active autoimmune disease in donor or patient
* Evidence of active grade II-IV acute GVHD or active extensive chronic GVHD
* Uncontrolled infection

Primary outcomes:
measure: To determine the maximum tolerated dose of allogeneic DC in combination with DLI in patents with a relapsed hematologic malignancy following allogeneic hematopoietic stem cell transplantation.
timeFrame: 4 years
Secondary outcomes:
measure: To assess clinical response after infusions of donor derived DC and donor lymphocytes
measure: To assess the immunologic impact of infusions of donor derived DC and donor lymphocytes.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Edwin Alyea, MD
role: PRINCIPAL_INVESTIGATOR
References: