A Two-Step Approach to Bone Marrow Transplant Using Cells From Two Partially-Matched Relatives
Condition: Hematologic Malignancy; Leukemia; Acute Lymphoblastic Leukemia; ALL; Acute Myelogenous Leukemia; AML; Chronic Lymphocytic Leukemia; CLL; Lymphoma; Hodgkin's Lymphoma; Non-hodgkin's Lymphoma; Myeloma
MeSH terms: Lymphoma; Leukemia; Neoplasms; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myeloid, Acute
Intervention: Total Body Irradiation (TBI); Donor Lymphocyte Infusion (DLI); Cyclophosphamide (CY); Tacrolimus; Mycophenolate Mofetil (MMF); Hematopoietic Stem Cell Transplant (HSCT)
Intervention description: TBI twice daily for 4 days and occurs 6 to 9 days prior to the transplant. Total radiation dose is 12 Gy.; DLI given 6 days prior to transplant (HSCT).; Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).; Tacrolimus is started the day before the transplant and stops a few months after transplant.; MMF is started the day before transplant and stops a few weeks after transplant.; CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed using donor cells from two related donors.
The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem cells.
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: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hematologic malignancy; leukemia; Acute lymphoblastic leukemia; ALL; Acute myelogenous leukemia; AML; Chronic lymphocytic leukemia; CLL; lymphoma; hodgkin's lymphoma; non-hodgkin's lymphoma; myeloma; allogeneic stem cell transplant; TJU 2-step; Hematopoietic stem cell transplant; HSCT; bone marrow transplant; Cyclophosphamide; MMF; Mycophenolate Mofetil

Summary:

      This phase II clinical trial studies how well two donors stem cell transplant work in
      treating patients with high-risk hematologic malignancies. After receiving radiation to help
      further treat the disease, patients receive a dose of donors' T cells. T cells can fight
      infection and react against cancer cells. Two days after donors' T cells are given, patients
      receive cyclophosphamide (CY) to help destroy the most active T cells that may cause tissue
      damage (called graft versus host disease or GVHD). Some of the less reactive T cells are not
      destroyed by CY and they remain in the patient to help fight infection. A few days after the
      CY is given, patients receive donors' stem cells to help their blood counts recover. Using
      two donors' stem cell transplant instead of one donor may be more effective in treating
      patients with high-risk disease and may prevent the disease from coming back.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Any patient with a hematologic malignancy with residual disease (morphological,
             cytogenetic, molecular, or radiographic) after treatment with 1 or more chemotherapy
             regimens in whom achievement of remission with additional chemoradiotherapy is felt to
             be unlikely or who is in 3rd or greater CR. Patients with marrow based diseases in
             which the marrow biopsy does not meet criteria for active disease (i.e. <5% blasts in
             acute leukemia) but who does not have full count recovery will be eligible for
             treatment on this high risk trial.

          2. Patients must have two related donors that meet an acceptable scenario as described
             above.

          3. Patients must adequate organ function:

               -  LVEF of >= 50%

               -  DLCO (adjusted for hemoglobin) >= 50% of predicted

               -  Adequate liver function as defined by a serum bilirubin =< 1.8, AST or ALT < 2.5X
                  upper limit of normal

               -  Creatinine clearance of >= 60 ml/min

          4. Karnofsky Performance Status of > 80 % on the modified KPS tool (see Appendix A).

          5. Patients must be willing to use contraception if they have childbearing potential.

          6. Able to give informed consent

        Exclusion Criteria:

          1. Modified KPS of < 80%

          2. >= 5 Comorbidity Points on the HCT-CI Index (See Appendix B)

          3. Class I or II antibodies against donor HLA antigens

          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, or unwillingness to use contraception if they have child bearing potential

          8. Patients with life expectancy of =< 6 months for reasons other than their underlying
             hematologic/oncologic disorder

          9. Alemtuzumab treatment within 8 weeks of HSCT admission.

         10. ATG level of >= 2 ugm/ml

         11. Patients with active inflammatory processes (such as flair of an autoimmune disease)
             including T max > 101, or active tissue inflammation are excluded.

         12. Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses
             specified in the treatment plan.