T-cell Depleted Alternative Donor Transplantation
Condition: Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Lymphomas; Bone Marrow Failure; Hemoglobinopathy; Immune Deficiency; Osteopetrosis
MeSH terms: Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Osteopetrosis; Myelodysplastic Syndromes; Bone Marrow Failure Disorders; Pancytopenia; Hemoglobinopathies; Immunologic Deficiency Syndromes
Intervention: CliniMACS® (T cell depletion)
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No
Keywords: T cell depleted; Matched unrelated donors; Haplocompatible donors

Summary:

      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.
    

Eligibility criteria:

        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 6.1.3.2 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.