Universal Donor Natural Killer Cells and ALT-803 in Treating Patients with Relapsed or Refractory Blood Cancer, Colon / Rectal Cancer, or Soft Tissue Sarcoma

Status: Temporarily Closed to Accrual


This phase I trial studies the best dose of universal donor natural killer cells when given together with superagonist interleukin-15:interleukin-15 receptor alphaSu / Fc fusion complex ALT-803 (ALT-803) in treating patients with blood cancer, colon / rectal cancer, or soft tissue sarcoma that has come back after a period of improvement or does not respond to treatment. Natural killer cells are a type of white blood cell that may kill tumor cells. ALT-803 may enhance natural killer cell survival and enable them to increase in number after infusion. Giving natural killer cells and ALT-803 may kill more tumor cells.

Eligibility Criteria

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 * 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 1 week prior to study entry; patients with prior stem cell transplant must be greater than 365 days post-transplant
  • Eastern Cooperative Oncology Group performance status (ECOG PS) =< 2
  • Serum total bilirubin < 2 mg/dl (except if known Gilbert syndrome AND normal transaminases)
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 2.5 x institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Pulmonary function (diffusion capacity of the lung for carbon monoxide [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; 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 cerebrospinal fluid (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; breastfeeding should be discontinued if the mother participates in this trial
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • 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)

Locations & Contacts


Case Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Folashade Otegbeye
Phone: 216-286-4443
Email: folashade.otegbeye@uhhospitals.org

Trial Objectives and Outline


I. To determine the maximum tolerated dose of ex vivo expanded non-human leukocyte antigen (HLA) matched donor natural killer (NK) cells in combination with ALT-803.


I. Describe safety profile / toxicity of combining ALT-803 with NK cell adoptive therapy.

II. Determine antitumor activity of allogeneic NK cells with ALT-803 support.

III. Determine if a lymphocyte depleting regimen is adequate for preventing early elimination of HLA-mismatched donor NK cells by host T-cells.

OUTLINE: This is a dose escalation study of natural killer cells.

PREPARATIVE REGIMEN: Patents receive cyclophosphamide intravenously (IV) and mesna IV on day -7 and fludarabine phosphate IV over 30 minutes daily (QD) on days -6 to -2.

NK CELL INFUSION: Patients receive NK cells IV on day 0 and day 14. Patients also receive superagonist interleukin-15:interleukin-15 receptor alphaSu/Fc fusion complex ALT-803 subcutaneously (SC) on days 0, 7, 14, and 21.

After completion of study treatment, patients are followed up at 28 days, 100 days, 6 months, and 12 months after the first NK cell infusion.

Trial Phase & Type

Trial Phase

Phase I

Trial Type


Lead Organization

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Folashade Otegbeye

Trial IDs

Primary ID CASE2Z16
Secondary IDs NCI-2017-00305
Clinicaltrials.gov ID NCT02890758