Trial of Allogeneic Stem Cell Transplants From HLA Compatible, Related and Unrelated Donors After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine For Adult Patients With Lymphohematopoietic Disorders
Condition: Allogeneic Stem Cell Transplant; Leukemia; Non-Hodgkins; Lymphoblastic Lymphoma; Myelodysplastic Syndrome; Paroxysmal Nocturnal Hemoglobinuria (PNH)
MeSH terms: Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemoglobinuria; Myelodysplastic Syndromes; Hemoglobinuria, Paroxysmal
Intervention: cytoreductive regimen followed by a CD34+E- selected allogeneic stem cell transplant
Intervention description: Myeloablative and will consist of hyperfractionated TBI - 1375 cGy administered in 11 doses of 125 cGy each over a total of four days, with three doses on three days and two doses on the last day, fludarabine 25 mg/m2 IV x 5 days, and thiotepa 5mg/kg IV x 2 days. Recipients of HLA identical related transplants will not receive ATG to promote engraftment. Recipients of HLA mismatched related or unrelated stem cells will receive ATG for two days prior to the transplant. G-CSF mobilized CD34+E- PBSCs obtained from the HLA compatible donor will be infused on day 0. Post transplantation G-CSF will be administered only if clinically indicated and should begin on or after d+7.
Patients will be clinically evaluated at each clinic visit for incidence and severity of acute and chronic GVHD and transplant associated morbidity. Sequential evaluation of functional reconstitution of hematopoiesis and immunity will be made as per the BMT Service guidelines.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: leukemia; non-Hodgkins; lymphoblastic lymphoma; myelodysplastic syndrome; paroxysmal nocturnal hemoglobinuria (PNH); cytoreductive regimen; allogeneic stem cell transplant

Summary:

      This is a phase II, single-center study to evaluate the efficacy of a novel cytoreductive
      regimen followed by CD34+E- selected T cell depleted allogeneic stem cell (or soybean
      agglutinated and E-rosetted BM) transplant as treatment for patients with acute and chronic
      leukemias, lymphoma and myelodysplstic syndrome/PNH. The impact of the change in conditioning
      regimen and use of CD34-selected T cell depleted PBSCs on transplanted related morbidity and
      mortality and disease free survival will be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven acute or chronic leukemia, non Hodgkins and lymphoblastic
             lymphoma or myelodysplastic syndrome

          -  HLA 6/6 or 5/6 antigen matched related or unrelated donor

          -  creatinine = normal or if not, CrCl > 60 ml/min/1.73ml

          -  total bilirubin < 2.5, AST < 2xnl, cardiac function > 50%

          -  pulmonary function - asymptomatic or if not DLCO > %50% (corrected for Hgb)

          -  Karnofsky performance status > 70%

          -  negative pregnancy test (where applicable)

          -  signed informed consent of patient and donor.

        Exclusion Criteria:

          -  Pregnancy or lactation

          -  unwillingness to comply with protocol treatment or follow-up

          -  uncontrolled infection

          -  HIV or HTLV positivity

          -  active CNS/skin disease