Clinical trial NCT01050764 (phase 1/phase 2, status: terminated)
Conditions: leukemia, acute, chronic myelogenous leukemia (cml), myelodysplastic syndrome (mds), non-hodgkin lymphoma (nhl), chronic lymphocytic leukemia (cll), acute myelogenous leukemia (aml), acute lymphoblastic leukemia (all)
ICD codes: D46.Z, D46.9, C94.6, D46.C, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, A87.2, K52.832, D72.111, C91.11, C91.12, C91.10
Drugs: regulatory t-cells, conventional t-cells, melphalan, thiotepa, anti-thymocyte globulin, rabbit, clinimacs cd34 reagent system
SMILES: [H][C@]12SCC(CSC3=NN=C(C)S3)=C(N1C(=O)[C@H]2NC(=O)CN1C=NN=N1)C(O)=O, N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O, CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1
Reason stopped: 
    safety
  
Eligibility criteria:

        Inclusion Criteria

        RECIPIENT

          -  Histopathologically-confirmed:

          -  Acute leukemia (in first remission with poor risk factors and molecular prognosis)

          -  Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11

          -  Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11)

          -  Acute leukemia with refractory disease or > Complete Remission (CR) 1

          -  Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase)

          -  Myelodysplastic syndrome (in high and high intermediate risk categories)

          -  Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous
             transplantation

          -  Refractory Chronic lymphocytic leukemia (CLL)

          -  At least 21 days from the end of most recent prior therapy to start of the transplant
             conditioning regimen

          -  Must be < 60 years old at time of registration.

          -  Karnofsky Performance Status (KPS) > 70%

        Must have related donor who is:

          -  Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci
             haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared
             haplotype in the graft-versus-host disease (GvHD) direction)

          -  No HLA-matched sibling or matched-unrelated donor is identified.

          -  Adequate cardiac and pulmonary function (left ventricular ejection fraction (LVEF) >
             45%, diffusing capacity of the lungs for carbon monoxide (DLCO) >50% corrected for
             hemoglobin)

          -  Serum creatinine < 1.5 mg/dL OR Creatinine clearance > 50 mL/min for those above serum
             creatinine at least 1.5 mg/dL

          -  Serum bilirubin < 2.0 mg/dL

          -  Alanine transaminase (ALT) < 2x upper normal limit (ULN) (unless secondary to disease)

          -  No prior myeloablative therapy or hematopoietic cell transplantation

        DONOR:

          -  Age ≤ 70 years

          -  Weight ≥ 25 kg.

          -  Medical history and physical examination confirm good health status as defined by
             institutional standards

          -  Seronegative for HIV Ag within 30 days of apheresis collection for:

          -  Hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR) +

          -  Hepatitis C ab or PCR+

          -  Genotypically haploidentical as determined by HLA typing

          -  Female donors (child-bearing potential) must have a negative serum or urine beta-human
             chorionic gonadotropin (HCG) test within 3 weeks of mobilization

          -  Capable of undergoing leukapheresis

          -  Has adequate venous access

          -  Willing to undergo insertion of a central catheter if leukapheresis via peripheral
             vein is inadequate

          -  Capable of agreeing to second donation of peripheral blood progenitor cell (PBPC) (or
             a bone marrow harvest) should the patient fail to demonstrate sustained engraftment
             following the transplant

          -  Institutional review board (IRB)-approved consent form signed by donor or legal
             guardian > 18 years of age

        Donor Selection in the priority order:

          -  Recipient's biological mother preferred, if available

          -  Other available haploidentical donors will be selected based upon the presence of
             natural killer (NK) alloreactivity between donor and recipient by high-resolution HLA
             typing of the C locus. An NK-alloreactive donor will be preferentially chosen.
             Recipients lacking a killer immunoglobulin-like receptor (KIR)-ligand present in the
             donor along with the corresponding KIR defines "NK alloreactivity".

          -  If more than one NK-alloreactive donor is available, preference is to cytomegalovirus
             (CMV)-seronegative donor

        Exclusion Criteria

        RECIPIENT:

          -  Suitable candidate for autologous transplantation or allogeneic transplantation with
             an available matched-related or matched-unrelated donor

          -  Seropositive for:

          -  HIV ab

          -  Hepatitis B sAg or PCR+

          -  Hepatitis C ab or PCR+

          -  History of invasive Aspergillosis

          -  Any active, uncontrolled bacterial, viral or fungal infection

          -  Uncontrolled central nervous system (CNS) disease involvement

          -  Lactating female

        DONOR:

          -  Evidence of active infection or viral hepatitis

          -  Factors of increased risk for complications from leukapheresis or granulocyte-colony
             stimulating factor (G-CSF) therapy

          -  Lactating female

          -  HIV-positive