Stem Cell Transplantation for Patients With Cancers of the Blood
This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body.
Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match.
Participants have a central intravenous (IV) line placed into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples. Treatment starts with a conditioning regimen of chemotherapy (fludarabine and cyclophosphamide) and total body irradiation to suppress immunity and prevent rejection of the donated stem cells. The day after chemotherapy ends, the stem cells are given through the central line. This is followed by transfusion of the donor's immune cells, which have been treated to remove cells that could cause severe GVHD. Also to minimize the risk of GVHD, patients are given cyclosporine. Not all participants receive the same amount of this drug; in order to determine how much immunosuppression is needed to protect against severe GVHD, the length of treatment with cyclosporine varies among patients, depending on when they entered the study and how well preceding patients did.
The average hospital stay for stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. The patient's referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, and 3 years after transplantation. After 3 years, participants are offered the opportunity to enroll in NHLBI's long-term evaluation and follow-up care protocol.
CML (Chronic Myelogenous Leukemia)
CLL (Chronic Lymphocytic Leukemia)
AML (Acute Myelogenous Leukemia)
ALL (Acute B-Lymphoblastic Leukemia)
MDS (Myelodysplastic Syndrome)
Procedure: Peripheral Blood Stem Cell Transplant
Device: CliniMACS and Theralux Systems
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Selective Depletion of Alloreacting T Cells Using a Photodepletion Technique to Prevent GVHD After HLA-Matched Peripheral Blood Stem Cell Transplantation for Subjects With Hematologic Malignancies|
- To determine if selective T cell depletion using the photodepletion procedure can substantially reduce the rate of severe acute GVHD (grade III/IV) after matched sibling transplantation followed by low-dose or no immunosuppression. [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
- Secondary objectives include determining the rate od standard transplant outcome variables: toxicity, relapse, graft rejection, disease free survival. [ Time Frame: 3 years maximum ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2007|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Procedure: Peripheral Blood Stem Cell Transplant
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on approaches in transplant techniques designed to decrease graft versus host disease (GVHD), increase the graft-versus-leukemia (GVL) effect, and/or reduce the risk for post-transplant graft rejection or disease relapse.
Ex vivo selective depletion of alloreacting T cells, hereafter referred as selective depletion (SD), represents a translational strategy aiming to reduce severe GVHD whilst preserving GVL. We found that selectively depleted transplants are safe to administer and associated with less severe acute GVHD. This protocol is designed to evaluate the safety and efficacy of photodepletion (PD) as an improved selective depletion procedure in the HLA-matched peripheral blood stem cell transplant setting and to determine whether post-transplant immunosuppression with cyclosporine is necessary to prevent severe GVHD after a photodepleted transplant.
The protocol will accrue subjects ages 18-75 who are diagnosed with a hematological malignancy where allogeneic stem cell transplantation from an HLA-matched sibling would be normally indicated. Diagnostic categories will include acute and chronic leukemias, myelodysplastic syndromes, B-cell lymphomas, multiple myeloma, and myeloproliferative syndromes.
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach (Kiadis Pharma). Older subjects will receive a lower dose of irradiation to reduce the regimen intensity.
To determine appropriate level of post transplant immunosuppression, we will utilize a three sequential de-escalation stage design involving 17 subjects per cohort (minimum 17, maximum 51 total evaluable subjects in study). Stopping rules for non-relapse mortality in each cohort will determine whether to continue to the next stage; to continue accumulating subjects at the same level; or to stop the protocol.
Cohort 1: Low dose cyclosporine until day 90 then dose tapered to stop within 2 weeks.
Cohort 2: If no severe GVHD is encountered in Cohort 1, the cyclosporine withdrawal will begin on day 45.
Cohort 3: If no severe GVHD is encountered in Cohort 2, cyclosporine will not be used in the post-transplant period.
Primary endpoints will be the incidence of acute grade III/IV GVHD at day 90. Secondary endpoints will be standard transplant outcome variables: toxicity, non relapse mortality and survival.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00467961
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Minocher M Battiwalla, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|