Clinical trial NCT00625729 (phase 1/phase 2, status: terminated)
Conditions: leukemia, lymphoma
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: cyclophosphamide, fludarabine phosphate
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Reason stopped: 
    no patients exhibited natural killer cell expansion (primary endpoint).
  
Eligibility criteria:

        Inclusion Criteria:

          -  Patient 18 years or older with a diagnosis of non-Hodgkin Lymphoma or chronic
             lymphocytic leukemia (NHL or CLL) and one of the following:

               -  Progression of NHL following at least 2 prior chemotherapy regimens, (must
                  contain rituximab for all NHL and fludarabine for follicular NHL) defined as:

                    -  failure to achieve partial remission (PR) with the last chemotherapy

                    -  disease progression within 6 months following last chemotherapy

               -  Progression of CLL/SLL (small lymphocytic lymphoma) following at least 2 prior
                  chemotherapy regimens (containing purine analogs ) in stage Rai III or IV or
                  symptomatic disease.

               -  Relapsed NHL or CLL following stem cell transplantation for whom the option of
                  donor lymphocyte infusion is not available or clinically indicated (e.g.
                  recipients of autologous or umbilical cord blood [UCB] transplants).

          -  Available related HLA-haploidentical (human leukocyte antigen) natural killer (NK)
             cell adult donor by at least Class I serologic typing

          -  Karnofsky performance status > 60%

          -  Measurable disease based on modified Response Evaluation Criteria In Solid Tumors
             (RECIST)

          -  Have acceptable organ function as defined within 28 days of enrollment:

               -  Hematologic: platelets ≥ 80,000 x 10^9/L; hemoglobin ≥ 9g/dL, unsupported by
                  transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10^9/L, unsupported by
                  granulocyte-colony stimulating factor or granulocyte-macrophage
                  colony-stimulating factor (G-CSF or GM-CS)F for 10 days or Neulasta for 21 days -
                  the hematologic requirements are waived for patients with inadequate counts due
                  to known bone marrow involvement by lymphoma who are otherwise eligible

               -  Renal: glomerular filtration rate (GFR) > 50 ml/min

               -  Hepatic: alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3 x
                  upper limit of normal and total bilirubin <3 mg/dl

               -  Pulmonary function: >50% corrected carbon monoxide diffusing capacity (DLCO) and
                  Forced Expiratory Volume in the first second (FEV1)

               -  Cardiac: no symptoms of uncontrolled cardiac disease, left ventricular ejection
                  fraction >40%

          -  Off prednisone or other immunosuppressive medications for at least 3 days prior to Day
             0

          -  Women of childbearing potential must agree to use adequate contraception (diaphragm,
             birth control pills, injections, intrauterine device [IUD], surgical sterilization,
             subcutaneous implants, or abstinence, etc.) for the duration of treatment.

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care.

        Exclusion Criteria:

          -  Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and
             there is no information on the excretion of agents into breast milk. All females of
             childbearing potential must have a blood test or urine study within 2 weeks prior to
             registration to rule out pregnancy. Women of childbearing age must use appropriate
             contraceptive method.

          -  Active central nervous system (CNS) lymphoma/leukemia

          -  Active serious infection (pulmonary infiltrates or lesions are allowed only after the
             appropriate diagnostic testing is negative for infection or appropriate therapy was
             initiated for probable infection)

          -  Pleural effusion - large enough to be detectable on the chest x-ray

          -  Allergy to rituximab or IL-2

          -  Human immunodeficiency virus (HIV) and associated non-Hodgkins lymphoma (NHL)

          -  Active concurrent malignancy (except skin cancer) requiring systemic therapy in the
             past 2 years

          -  Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder

          -  Positive hepatitis B surface antigen (HBsAg). If Hepatitis B core antibody (HBcAb) is
             positive, Hepatitis B deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR)
             will be evaluated. Positive anti HBcAb and undetectable viral load does not exclude
             the patient.

          -  Any experimental therapy in the past 30 days

        Donor Selection:

          -  Related donors (sibling, parent, offspring, parent or offspring of an HLA identical
             sibling) ≥ age 18 years

          -  Able and willing to undergo lymphapheresis

          -  HLA-haploidentical donor/recipient match. If time permits and multiple donors are
             available, preference will be given to the Killer-cell Immunoglobulin-like Receptors
             (KIR) ligand mismatched donor (as predicted by HLA typing).

          -  HIV-1, HIV-2 negative, Human T-lymphotropic virus Type I (HTLV-1), HTLV-2 negative,
             West Nile virus (WNV) negative, Hepatitis B and C negative

          -  Adequate organ function defined as:

               -  Hematologic: CBC/diff/platelet count near normal limits,

               -  Hepatic: ALT < 2 x upper limit of normal,

          -  Not pregnant or lactating

          -  In general good health as determined by the study physician

          -  Able to give informed consent