A Phase 1 interventional study of decitabine and natural killer cell therapy in Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q) and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), sponsored by Sumithira Vasu. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-09.
Sponsored by Sumithira Vasu · Phase 1, Interventional, and Treatment
This pilot trial studies decitabine, donor natural killer cells, and aldesleukin in treating patients with acute myeloid leukemia that has come back after previous treatment (relapsed) or has not responded to previous treatment (refractory). Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving donor natural killer cells after decitabine may boost the patient's immune system by helping it see the remaining cancer cells as not belonging in the patient's body and causing it to destroy them (called graft-versus-tumor effect). Aldesleukin may stimulate natural killer cells to kill acute myeloid leukemia cells. Giving decitabine, donor natural killer cells, and aldesleukin may be a better treatment for acute myeloid leukemia.
PRIMARY OBJECTIVES:
I. To determine the feasibility and safety of decitabine followed by natural killer (NK) cells and IL-2 (Interleukin).
II. To define the specific toxicities and the dose limiting toxicity (DLT) of decitabine plus NK cells and IL-2.
III. To determine the feasibility and safety of manufacturing processes for NK cells.
SECONDARY OBJECTIVES:
I. To determine the overall response rate (ORR). II. To determine the rate of complete remission (CR) to this regimen of decitabine plus NK cells and IL-2 (interleukin) in acute myeloid leukemia (AML).
TERTIARY OBJECTIVES:
I. To correlate the biological activity of decitabine as in upregulating ligands that mediate susceptibility to NK mediated cytotoxicity.
II. To characterize the biological activity of infused NK cells and persistence as defined by NK chimerism.
III. To evaluate if decitabine has immunosuppressive properties or modulates changes in endogenous cytokines in patients.
OUTLINE:
Patients receive decitabine intravenously (IV) over 60 minutes on days -4 to 0 and undergo infusion of allogeneic NK cells on day 0. Beginning 1 hour after infusion allogeneic NK cells, patients also receive aldesleukin subcutaneously (SC) every other day for 6 doses.
After completion of study treatment, patients are followed up for 30 days.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 8 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
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Patients with relapsed or refractory AML
Exclusion Criteria:
Patients receive decitabine IV over 60 minutes on days -4 to 0 and undergo infusion of allogeneic NK cells on day 0. Beginning 1 hour after infusion allogeneic NK cells, patients also receive aldesleukin SC every other day for 6 doses.
Drug: decitabine · Biological: natural killer cell therapy · Biological: aldesleukin · Other: laboratory biomarker analysis
20 mg/m2 Given IV (intravenous) for 5 days over 60 minutes
Also known as: 5-aza-dCyd, 5AZA, DAC
Undergo infusion of allogeneic NK cells on day 0
Given SC
Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Correlative studies
Incidence of toxicities graded by using the Common Terminology Criteria for Adverse Events (CTCAE) version 4
Will be summarized descriptively. Infusion toxicity and tolerability will be summarized by frequencies of type of reaction and will be tabulated for each cohort of patients treated under a specific approach and manufacturing process.
Time frame: Up to 28 days post NK infusion
DLTs (dose limiting toxicites) defined by occurrence of life-threatening consequences within 4 hours of infusion graded using CTCAE version 4.0
Infusion toxicity and tolerability will be summarized by frequencies of type of reaction and will be tabulated for each cohort of patients treated under a specific approach and manufacturing process.
Time frame: Within 4 hours of infusion
Therapeutic response of these combinations of agents in patients ORR
Therapeutic response assessed using International Working Group criteria
Time frame: Up to 30 days post-treatment
Detect infused NK cells in vivo by donor-specific short tandem repeats in the Histocompatibility laboratory at Ohio state University.
Infused NK cells will be detected in vivo by donor-specific short tandem repeats in the Histocompatibility laboratory at Ohio state University. Prior to NK cell infusion, donor and recipient samples will be evaluate for unique short-tandem repeats. After the NK cell infusion, samples will be drawn at different time points( days 7, 14 and 21) to determine if circulating NK cells in the recipient are derived from the donor or recipient.
Time frame: Up to 21 days
Plan to share: No
This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.
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Sumithira Vasu