Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803

Inclusion Criteria:

* Patients must have histologic confirmation of relapsed and or refractory hematologic malignancy, locally advanced or metastatic colon/rectal carcinoma, or refractory and/or relapsed soft tissue sarcomas and have failed at least one standard line of therapy.
* Patients will be eligible if they have either declined standard treatment regimens or if there is no standard approach to curative salvage therapy per National Comprehensive Cancer Network (NCCN) guidelines in the setting of relapsed/refractory disease.
* In addition, patients for whom a potential 29-day delay in treatment will not interfere with the subject's potential therapeutic options can be eligible per the treating physician's discretion.

Malignancies can include:

* Acute myeloid leukemia
* Myelodysplastic syndrome
* Acute lymphoblastic leukemia
* Chronic myeloid leukemia
* Chronic lymphocytic leukemia
* Non Hodgkin Lymphoma
* Hodgkin Lymphoma
* Myeloproliferative syndromes
* Plasma cell myeloma
* Colon/rectal carcinoma
* Soft tissue sarcomas including but not limited to Ewing's sarcoma and Rhabdomyosarcoma

  * Patients must have recovered from acute toxicities of prior chemotherapy or stem cell transplant. Any prior non-hematologic vital organ toxicity (cardiac, pulmonary, hepatic, renal) of previous therapy must have resolved to grade 1 or less.
  * All previous chemotherapy or radiation must be completed at least 3 weeks prior to study entry. Immunologic therapy must be completed at least 3 weeks prior to study entry. Patients with prior stem cell transplant must be greater than 365 days post-transplant.
  * Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  * Organ function criteria (There is no exclusion for the presence of cytopenias),

    * Serum total bilirubin \<2 mg/dl (except if known Gilbert syndrome and normal transaminases)
    * Aspartate aminotransferase (AST) (SGOT) \< 2.5 X institutional upper limit of normal
    * Alanine aminotransferase (ALT) (SGPT) \< 2.5 X institutional upper limit of normal
    * Pulmonary function (DLCO) \>40% of the expected value corrected for alveolar volume and hemoglobin
    * Serum Creatinine ≤ 1.5 X institutional upper limit of normal
  * Subjects must have the ability to understand and the willingness to sign a written informed consent document.
  * Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 4 weeks prior to study entry and for the duration of study participation. Women of child-bearing age must have documented negative pregnancy test prior to start of lympho-depleting regimen.

Exclusion Criteria:

* Subjects receiving any other investigational agents.
* Subjects for whom a potential 29-day delay in treatment will interfere with the subject's potential therapeutic options.
* Patients with untreated malignant involvement of the central nervous system (CNS) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Head imaging will be necessary to document absence of CNS involvement in patients with colon/rectal cancer and soft tissue sarcomas. Patients with hematologic malignancies who have undergone treatment for malignant involvement of the CNS must have no evidence of residual disease by imaging or CSF sampling prior to study enrollment.
* History of allergic reactions to chemotherapy agents used in this protocol as part of lymphodepletion regimen (Fludarabine and Cyclophosphamide)
* Patients with uncontrolled intercurrent illness including, but not limited to ongoing active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or breastfeeding women are excluded from this study.
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic agents. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
* Chronic active untreated hepatitis B or C infection.
* Recipients of previous allogeneic transplants who have rash involving more than 10% body surface area attributed to graft versus host disease (GVHD) (\> Grade 1 GVHD of skin). Stem cell transplant recipients will be excluded if they are still receiving immunosuppression including steroids for GVHD or have active GVHD in any organ (except for Grade 1 only of skin, not requiring treatment).