Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases
Condition: Chronic Leukemia; Acute Leukemia; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Myelodysplastic Syndrome
MeSH terms: Leukemia; Hodgkin Disease; Myelodysplastic Syndromes
Intervention: Peripheral Blood Stem Cell Transplant
Intervention description: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1.
Fludarabine 30 mg/m^2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: CML; CLL; AML; ALL; MDS; HD; NHL; MFB; P.vera; Essential Thrombocytosis

Summary:

      In this study, patients will receive a myeloablative preparative regimen consisting of
      fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized
      peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All
      patients will receive post-transplant Cy in addition to standard post transplant
      immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially
      identical to the prior study, with the exception of the substitution of TBI for Busulfan. The
      investigators hypothesize that this change will significantly reduce the risk of HC, while
      maintaining the efficacy of the transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  No available matched related or unrelated donor OR a matched related or unrelated
             donor that is unavailable in the time frame necessary

          -  Availability of a 3/6 or 5/6 matched (HLA-A, B, DR) related donor

          -  Donor must have a negative HLA cross-match in the host vs. graft direction

          -  Donor must be willing to donate mobilized peripheral blood stem cells

          -  Age 18 to </=60 years

          -  Karnofsky Status >/= 70%

          -  Must have one of the following high-risk malignancies

          -  Chronic Myelogenous Leukemia (CML) in chronic phase, resistant and/or intolerant to
             TKI

          -  CML in accelerated phase

          -  CML blast crisis that has entered into 2nd Chronic phase following induction

          -  Acute Myelogenous Leukemia (AML) in 2nd or subsequent complete remission (CR)

          -  AML primary induction failure but subsequently in CR

          -  AML in 1st CR with poor risk cytogenetics or arising from preceding hematologic
             disease

          -  AML with marrow blasts <5% but persistence of minimal residual disease by flow
             cytometry, cytogenetics or FISH

          -  Myelodysplastic Syndrome (MDS) that is treatment related

          -  MDS that has monosomy 7 or complex cytogenetics

          -  MDS with IPSS score of 1.5 or greater

          -  Chronic myelomonocytic leukemia (CMML)

          -  Acute Lymphocytic Leukemia/lymphoblastic lymphoma (ALL) in 2nd or subsequent complete
             remission (CR)

          -  ALL with poor-risk karyotype [t(9;22) or bcr-abl fusion, t(4;11) or other MLL
             translocation] and in 1st CR

          -  ALL with marrow blasts < 5% but persistence of minimal residual disease by flow
             cytometry, cytogenetics or FISH

          -  Chronic Lymphocytic Leukemia (CLL)/Prolymphocytic Leukemia (PLL) with previously
             treated disease that has either relapsed or failed to respond adequately to
             conventional-dose therapy including purine analogs AND in the opinion of the
             transplant physician is unlikely to benefit from reduced intensity transplantation due
             to the presence of one or more high risk features (i.e. bulky tumor masses, B
             symptoms, and/or inadequate response to salvage chemotherapy)

          -  Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and
             intermediate-grade/diffuse) with previously treated disease that has either relapsed
             or failed to respond adequately to conventional-dose therapy or autologous
             transplantation AND in the opinion of the transplant physician is unlikely to benefit
             from reduced intensity transplantation due to the presence of one or more high risk
             features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage
             chemotherapy)

          -  Advance Myelofibrosis, Primary or Post-Polycythemia Vera/Essential Thrombocythemia.
             Patients must have one of more of the following accelerate phase features, which have
             been associated with a median overall survival of </= 15 months

          -  Blood or bone marrow blasts >/= 10%

          -  Platelets < 50 x 10*9/L

          -  Chromosome 17 aberrations

        Exclusion Criteria:

          -  Patients will not be excluded on the basis of sex, racial or ethnic background

          -  Poor cardiac function: Left ventricular ejection fraction < 45%

          -  Poor pulmonary function: FEV1 and FVD < 60% predicted

          -  Poor liver function: bilirubin >/= 2.5 mg/dl (not due to hemolysis, Gilbert's or
             primary malignancy), AST/ALT > 3x ULN

          -  Poor renal function: Creatinine >/= 2.0 mg/dl or creatinine clearance (calculated
             creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault
             formula: 140-age (yrs) x smaller of actual weight vs ideal body weight (kg)/72 x serum
             creatinine (mg/dl)

          -  HIV positive

          -  Women of childbearing potential who currently are pregnant or who are not practicing
             adequate contraception

          -  Patients who have any debilitating medical or psychiatric illness which would preclude
             their giving informed consent or their receiving optimal treatment and follow-up.

          -  Prior irradiation therapy rendering patient ineligible for TBI