Acute Lymphoblastic Leukemia | T-cell Depleted Alternative Donor Transplantation
Acute Lymphoblastic Leukemia research study
What is the primary objective of this study?
The primary purpose is to determine the ability of CD34+ selection and T cell depletion using the CliniMACS® device to prevent severe acute graft-versus-host disease (GVHD) in patients receiving a stem cell transplant from an alternative (unrelated and mismatched related) donor. The secondary objectives include evaluation of engraftment, immune recovery, and post-transplant infections. Patients requiring stem cell transplants for either malignant (cancerous) or non-malignant disease will be included in the study. The recipients will be grouped into one of two groups based on whether the donor is mismatched related (Cohort A) or unrelated (Cohort B). The patient will receive a conditioning regimen including chemotherapy drugs and/or total body irradiation based on the disease for which the transplant is performed.
Who is eligible to participate?
Inclusion Criteria: - Age < 30 years - Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, and immunodeficiencies. - Patients with acute lymphoblastic leukemia must be in morphological remission (< 5% blasts) at the time of transplant. Patients with acute non-lymphocytic leukemia will preferably be in morphologic remission but may be enrolled when aplastic after chemotherapy or with < 20% blasts. Patients with lymphoma must be in complete or close to complete remission (if residual adenopathy, PET scan must be negative or only have slight uptake, eg. SUV < 2). - Patients must lack a healthy HLA-identical related donor of at least one year of age. - Patient must have a mismatched related or an unrelated donor who is: 1. Able to receive G-CSF and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter, 2. Healthy, 3. Willing, 4. For recipients of an unrelated donor transplant, recipient eligibility will be restricted as follows if in the judgment of the recipients' transplant physician, the recipient cannot receive a transplant with combined positive and negative fractions as described in Section 22.214.171.124 or an unmanipulated PBSC product. 5. Meets eligibility criteria for donors. - If only one mismatched related relative is available, an acceptable unrelated donor must be identified as a backup. - Patient or authorized guardian must sign informed consent for this study. Exclusion Criteria: - Patient with an anticipated life expectancy of < 1 month - Active infectious hepatitis or CMV infection - HIV or HTLV-I/II infection - Serious infection (bacterial, fungal, viral) within the last 4 weeks - Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used. - Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used. - Pulmonary diffusion capacity (adjusted for Hgb), FEV1, or FVC <60% of predicted or O2 sat < 94% if unable to perform PFTs; can be lower if a reduced intensity conditioning regimen is used. - Serum ALT > 3 x upper limit of normal (can be up to 5 x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2. The bilirubin criteria for sickle cell disease patients is direct bilirubin >2x upper limit of normal. - Performance score (Lansky/Karnofsky) < 50 - Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
Bone Marrow Failure
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Device:CliniMACS® (T cell depletion)Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
CliniMACS® (T cell depletion)Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device.
Start Date: August 2009
Completed Date: November 2016
Phase: Phase 2
Primary Outcome: Number of Participants With Severe Graft vs. Host Disease (GVHD).
Secondary Outcome: Number of Participants With Engraftment and Time to Engraftment
Study sponsors, principal investigator, and references
Principal Investigator: Andrew Gilman, MD
Lead Sponsor: Andrew Gilman