Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor
Condition: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Neoplasms, Plasma Cell; Multiple Myeloma; Plasmacytoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Anemia, Aplastic
Intervention: Total Body Irradiation (TBI); Donor Lymphocyte Infusion (DLI); Cyclophosphamide; Mycophenolate Mofetil (MMF); Tacrolimus; Hematopoietic stem cell transplantation (HSCT)
Intervention description: Total body irradiation is given in 8 fractions over 4 days (total dose of 12 Gy).; After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days.; Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days; Started the day before the transplant to prevent graft versus host disease (GVHD); Started the day before the transplant to prevent graft-versus-host disease (GVHD); One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-donor stem cell product. This is the day of transplant.
The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia; Hematopoietic stem cell transplant (HSCT); myeloablative haploidentical HSCT; graft versus host disease (GVHD)

Summary:

      The primary hypothesis of this research study is that patients in remission undergoing
      myeloablative haploidentical hematopoietic stem cell transplantation (HSCT) on the Thomas
      Jefferson University (TJU) 2 Step treatment regimen will have a disease-free survival (DFS)
      rate at 1 year that is the same or better than the historical DFS of patients with similar
      diagnoses and ages undergoing matched sibling HSCT. Based on a review of the literature a DFS
      rate of 50% or better at 1 year would meet the criterion for an effective alternative
      therapy. A DFS rate of 75% or better would imply superior efficacy of the TJU 2 Step approach
      over T-replete matched sibling HSCT.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Any patient with a hematologic or oncologic diagnosis without morphological evidence
             of disease in which allogeneic HSCT is thought to be beneficial.

               -  Diagnoses include:

             Acute Myeloid Leukemia Myelodysplastic Syndromes Biphenotypic Leukemia Acute
             Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Lymphocytic Leukemia Plasma Cell
             Neoplasms Lymphoma Hodgkin Disease Aplastic Anemia

          2. Patients must have a related donor who is a two or more allele mismatch at the HLA-A;
             B; C; DR loci.

          3. Patients must adequate organ function:

               -  LVEF of > or = 50%

               -  DLCO > or = 50% of predicted corrected for hemoglobin

               -  Adequate liver function as defined by a serum bilirubin < or = 1.8, AST or ALT <
                  or = 2.5X upper limit of normal

               -  Creatinine clearance of > or = 60 ml/min

          4. Performance status > or = 70% (TJU Karnofsky)

          5. HCT-CI Score < 5 Points

          6. Patients must be willing to use contraception if they have childbearing potential

          7. Able to give informed consent

        Exclusion Criteria:

          1. Performance status < or = 70% (TJU Karnofsky)

          2. HCT-CI Score > 5 Points

          3. Combination of Performance status of < 80% (TJU Karnofsky) and an HCT-CI of 4 points
             or more.

          4. HIV positive

          5. Active involvement of the central nervous system with malignancy

          6. Psychiatric disorder that would preclude patients from signing an informed consent

          7. Pregnancy

          8. Patients with life expectancy of < or = 6 months for reasons other than their
             underlying hematologic/oncologic disorder

          9. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or
             who have recently received horse or rabbit ant-thymocyte globulin and have an ATG
             level of > or = 2 ugm/ml

         10. Patients who cannot receive cyclophosphamide

         11. Patients with evidence of another malignancy, exclusive of a skin cancer that requires
             only local treatment, should not be enrolled on this protocol.