Haploid Allogeneic Transplant Using the CliniMACS System
Condition: Acute Myelogenous Leukemia (AML) - Relapsed, Primary Refractory Disease or Poor Risk Factors; Chronic Myelogenous Leukemia (CML) - Accelerated or Second Chronic Phase; Myelodysplastic Syndrome (MDS) - High and Intermediate Risk; Non-Hodgkin's Lymphoma (NHL); Chronic Lymphocytic Leukemia (CLL) - Refractory
MeSH terms: Leukemia; Lymphoma, Non-Hodgkin; Preleukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: CliniMACS System
Intervention description: The CliniMACS System is a cell selection device consisting of the following components:
Computer-controlled instrument;
Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix)
Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle)
Wash buffer
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      To assess the proportion of patients with donor neutrophil engraftment within 30 days of
      allogeneic transplant. To assess the incidence of acute GvHD during the first 100 days after
      transplantation.
    

Eligibility criteria:

        RECIPIENT INCLUSION CRITERIA

        Histopathologically-confirmed diagnosis of hematological or lymphatic malignancy, defined
        as one of the following:

          -  Acute myeloid leukemia (AML) as primary refractory disease, or in relapse

          -  Acute leukemia in first remission with poor risk factors and molecular prognosis

          -  AML with -5,-7, t(6;9), tri8, -11

          -  Acute lymphocytic / lymphoblastic leukemia (ALL) with Phil+ t(9;22),(q34;q11.2), and
             t(4:11)(q21;23)

          -  Chronic myelogenous leukemia (CML in accelerated, second chronic phase

          -  Myelodysplastic syndrome with high intermediate to high risk categories

          -  Non-Hodgkin's lymphoma (NHL)

          -  Chronic lymphocytic leukemia (CLL), Refractory < 50 years old at time of registration
             Donor is related Donor is genotypically-matched and haploidentical for HLA-A, B,C and
             DRB1, DQ loci Donor differs for 2 or 3 HLA alleles on the unshared haplotype in the
             GvHD direction No HLA-matched sibling or matched unrelated donor is identified ECOG
             performance status not more than 2 LVEF > 45% DLCO > 50% corrected for hemoglobin
             Serum creatinine

          -  < 1.5 mg/dL OR

          -  creatinine clearance > 50 mL/min for those above serum creatinine of 1.5 mg/dL serum
             bilirubin < 2.0 mg/dL ALT < 2x ULN (unless secondary to disease) Females of
             childbearing potential must have a negative serum or urine beta-HCG test within 3
             weeks of registration No prior cancer within 5 years with the exception of
             surgically-cured, non-melanoma skin cancer or in situ cancer of the cervix No prior
             myeloablative therapy or transplant Duly-executed informed consent

        RECIPIENT EXCLUSION CRITERIA Suitable candidate for autologous transplantation
        Participation in other investigational drugs or devices trials that might influence the
        study endpoints Evidence of active hepatitis Evidence of active cirrhosis HIV-positive
        History of invasive aspergillosis Presence of any other uncontrolled, active infection, ie,
        bacterial, viral or fungal Uncontrolled CNS involvement Documented allergy to murine
        proteins Documented allergy to iron dextran Lactating female Female of child-bearing
        potential unwilling to implement adequate birth control Medical problem /
        neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with
        the medical regimen and/or to tolerate transplantation, in the opinion of the principal
        investigator Medical problem / neurologic/psychiatric dysfunction which would prolong
        hematologic recovery and place the recipient at unacceptable risk, in the opinion of the
        principal investigator would .

        DONOR INCLUSION CRITERIA Age < 60 years Weight > 25 kg Medical history and physical
        examination confirm good health status as defined by institutional standards Within 30 days
        of apheresis collection, seronegative for HIV assessed as HIV Ag; HIV 1+2 Ab; or HTLV I/II
        Ab Within 30 days of apheresis collection, seronegative for hepatitis assessed as HBsAg;
        HBcAb (IgM and IgG); or HCV Ab Within 30 days of apheresis collection, seronegative for
        syphilis assessed as RPR Genotypically haploidentical as determined by HLA typing Female
        donors of child-bearing potential must have a negative serum or urine beta-HCG test within
        3 weeks of mobilization Capable of undergoing leukapheresis Has adequate venous access
        Willing to undergo insertion of a central catheter should leukapheresis via peripheral vein
        be inadequate Agreeable to second donation of PBPC (or a bone marrow harvest) should the
        recipient fail to demonstrate sustained engraftment following the transplant Duly-executed
        informed consent Screened for CMV seroreactivity

          -  Must be seronegative donor if recipeint is seronegative.

          -  Otherwise the donor will be selected on the ability of NK cell alloreactivity based
             upon HLA typing results and donors who are capable of NK cell alloreactivity will be
             used preferentially.

        DONOR EXCLUSION CRITERIA Evidence of active infection (including urinary tract infection,
        or upper respiratory tract infection) Evidence of hepatitis (on screening) Medical,
        physical or psychological reason which makes the donor unlikely to tolerate or cooperate
        with growth factor therapy and leukapheresis Factors placing donor at increased risk for
        leukapheresis or G-CSF-related complications Lactating female Female of child-bearing
        potential unwilling to implement adequate birth control HIV-positive