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Donor Natural Killer Cell Therapy in Treating Patients with Recurrent or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Trial Status: Active

This phase I trial studies the best dose of donor natural killer (NK) cell therapy and to see how well it works in treating patients with acute myeloid leukemia that has come back (recurrent) or has not responded to treatment (refractory), or myelodysplastic syndrome. Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body’s immune system and may interfere with the ability of cancer cells to grow and spread.

Inclusion Criteria

  • Patients with one of the following diagnoses: * Relapsed or primary refractory acute myeloid leukemia (AML), including ** Patients with relapsed AML after allogeneic stem cells transplantation, including those who have received donor lymphocyte infusions ** Isolated central nervous system (CNS) or extramedullary disease ** Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease OR * Myelodysplastic syndrome ** >= 6% blasts, including patients who have received prior hypomethylating agents
  • Karnofsky or Lansky performance scale (PS) greater or equal to 70, or, Eastern Cooperative Oncology Group (ECOG) score 0-2
  • Serum creatinine =< 2 mg/dl and/or creatinine clearance greater or equal than 40 cc/min
  • Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of expected, corrected for hemoglobin
  • Total bilirubin =< 2 mg/dl or =< 2.5 x upper limit of normal (ULN) for age (unless Gilbert's syndrome)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN for age
  • Left ventricular ejection fraction >= 40%
  • Patients with seizure disorder may be eligible if seizures well controlled
  • Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential (non-childbearing potential defined as premenarchal, greater than one year post-menopausal, or surgically sterilized)
  • Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the investigator
  • Ability to understand and willingness to sign the written informed consent document
  • Negative serology for human immunodeficiency virus (HIV)
  • Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible

Exclusion Criteria

  • Investigational therapies in the 3 weeks prior to beginning treatment on this protocol
  • Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine, decitabine or cytarabine
  • Uncontrolled infection, defined as an infection which has not resolved spontaneously or does not show evidence of significant resolution after initiating appropriate therapy. Asymptomatic viremia such as cytomegalovirus (CMV), human papillomavirus (HPV), BK virus, hepatitis C virus (HCV), hepatitis B virus (HBV), etc. is NOT considered as an exclusion criteria
  • Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
  • Active graft versus host disease (GVHD)
  • Patient on corticosteroids to control GVHD
  • Patients on systemic steroids for asthma and prednisone dose is > 20 mg/day or > 0.25 mg/kg, whichever is higher will be excluded
  • Patients with donor-specific antibodies with mean fluorescence intensity (MFI) > 5000 will be ineligible


Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Sumithira Vasu
Phone: 614-293-8197


I. To determine the recommended phase II dose of NK cells.

II. To determine the overall response rate (complete response [CR], CR with incomplete hematologic recovery [CRi] & morphologic leukemia-free state [MLFS]).


I. To determine percentage of patients with measurable residual-negative remission.

II. To determine percentage of patients proceeding to an allogenic transplant.

III. Estimate the median time to neutrophil and platelet count recovery.

IV. Estimate the median duration of remission.

V. Estimate the incidence of infectious complications.

VI. To determine the percentage of patients with progression free survival.

VII. To determine the percentage of patients with overall survival.


I. Determine the persistence of ex-vivo expanded, off-the-shelf, third-party NK cells.

II. Characterize in vivo expansion of third-party NK cells and if it differs based on the conditioning regimen as defined by NK chimerism assay.

III. Determine the immunophenotype and function of expanded cells.

IV. Chimerism analysis in patients who have had post-transplant relapses.

OUTLINE: This is a dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells.

INDUCTION: Patients are assigned to 1 of 2 arms.

COHORT I: Patients who are < 60 years old, are able to tolerate intensive chemotherapy, and not insensitive to cytarabine receive fludarabine intravenously (IV) and cytarabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients who are >= 60 years old, unable/unwilling to tolerate intensive chemotherapy, or disease insensitive to cytarabine (tp53, TET2 mutations) receive fludarabine IV on days -5 to -2 and decitabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity.

All patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells via infusion on days 0, 2, 4, 7, 9, and 11.

After completion of study treatment, patients are followed up to day 56.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Ohio State University Comprehensive Cancer Center

Principal Investigator
Sumithira Vasu

  • Primary ID OSU-18336
  • Secondary IDs NCI-2019-05150, 2019C0170
  • ID NCT04220684