Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Haploidentical Donor
Condition: Hematopoietic/Lymphoid Cancer
MeSH terms: Hematologic Neoplasms
Intervention: Total-Body Irradiation (TBI); Donor Lymphocyte Infusion (DLI); Cyclophosphamide; Allogeneic hematopoietic stem cell transplantation (HSCT); Mycophenolate mofetil
Intervention description: Undergo TBI; Undergo DLI; Given IV; Undergo CD34+ selected allogeneic HSCT; Given IV
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well total-body irradiation, donor lymphocyte infusion, and
      cyclophosphamide before donor stem cell transplant works in treating patients with high-risk
      hematologic malignancies. Giving total-body irradiation, donor lymphocyte infusion, and
      chemotherapy before a donor stem cell transplant helps stop the growth of cancer and abnormal
      cells and helps stop the patient's immune system from rejecting the donor's stem cells. When
      certain stem cells from a donor are infused into the patient they may help the patient's bone
      marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the
      transplanted cells from a donor can make an immune response against the body's normal cells.
      Removing the T cells from the donor cells before transplant and giving tacrolimus and
      mycophenolate mofetil may stop this from happening.
    

Eligibility criteria:

        Inclusion Criteria:

          1. This treatment is for patients with high risk hematologic malignancies. High risk is
             defined as:

               -  Any patient with a hematologic malignancy with residual disease after treatment
                  with 1 or more chemotherapy regimens in whom achievement of remission with
                  additional chemoradiotherapy is felt to be unlikely

               -  Patients without morphologic evidence of disease but with high risk features
                  which would predict for relapse despite remission at HSCT such as adverse
                  cytogenetics, 3rd or greater CR (complete response), or failure to recover
                  peripheral blood counts to normal ranges. While these patients do not have
                  detectable disease by current methods, like all patients they have non-detectable
                  disease which in their case is highly aggressive.

          2. Patients must have one related donor who is HLA (human leukocyte antigen) mismatched
             in the GVHD direction at two or more HLA loci

          3. Patients must adequate organ function:

               -  LVEF (left ventricular ejection fraction) of >50 %

               -  Diffusing capacity of the lungs for carbon monoxide (DLCO) (adjusted for
                  hemoglobin) >50 % of predicted and forced expiration to the full FEV-1 >50 %

               -  Adequate liver function as defined by a serum bilirubin <1.8, AST (aspartate
                  aminotransferase) or ALT (alanine aminotransferase) < 2.5X upper limit of normal

               -  Creatinine clearance of > 60 ml/min

          4. Karnofsky Performance Status (KPS) of > 80% on the modified (KPS) tool

          5. Patients must be willing to use contraception if they have childbearing potential

          6. Able to give informed consent

        Exclusion Criteria:

          1. Modified (KPS) Karnofsky Performance status of <80%

          2. > 5 Comorbidity Points on the Hematopoietic cell transplantation - specific
             comorbidity (HCT-CI) Index (See Appendix B)

          3. Class I or II antibodies against donor human leukocyte antigens (HLA)

          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. Anti-thymocyte globulin (ATG) level of > 2 ugm/ml

         11. Patients with active inflammatory processes 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