Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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Brief Title

Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

Phase I Study of Decitabine and Haplo-identical Natural Killer Cells in Acute Myeloid Leukemia (AML)

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Incidence of toxicities graded by using the Common Terminology Criteria for Adverse Events (CTCAE) version 4

Secondary Outcome

 Therapeutic response of these combinations of agents in patients ORR

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

decitabine

Study Arms / Comparison Groups

 Treatment (decitabine, allogeneic NK cells, aldesleukin)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

8

Start Date

April 21, 2015

Completion Date

December 20, 2019

Primary Completion Date

December 6, 2017

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with relapsed or refractory AML

               -  Patients without a response after two cycles of decitabine

               -  Patients with primary refractory AML (persistent disease after standard induction
                  with 7+3) or relapsed AML

               -  Patients who have relapsed post-allogeneic transplant

          -  Patients with secondary AML or therapy related disease (t-AML) are eligible; patients
             who received decitabine or 5-azacytidine as prior treatment for myelodysplastic
             syndrome (MDS) remain eligible

          -  Patients with central nervous system (CNS) leukemia are eligible as long as they have
             received treatment and most recent cerebrospinal fluid (CSF) analysis is negative for
             leukemia

          -  If the patient has co-morbid medical illness, life expectancy attributed to the
             comorbid illness must be greater than 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Total bilirubin < 2.0 mg/dL

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) <
             2.5 X institutional upper limit of normal

          -  Creatinine < 2.0 mg/dL

          -  New York Heart Association (NYHA) congestive heart failure (CHF) class II or better

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; if the patient does not agree, the patient is not
             eligible; should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately

          -  Ability to understand and willingness to sign the written informed consent document

          -  Human immunodeficiency virus (HIV) infection without acquired immune deficiency
             syndrome (AIDS)-defining criteria are eligible

          -  DONOR: Donors must be human leukocyte antigen (HLA)-haploidentical first-degree
             relatives of the patient; eligible donors include biological parents, siblings or
             half-siblings, or children

          -  DONOR: Donor must be in general good health and eligible for apheresis as determined
             by the medical provider

          -  DONOR: HLA-haploidentical donor/recipient match by at least class I serologic typing
             at the HLA-A and B loci

          -  DONOR: Willing and able to provide informed consent

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study

          -  Patients receiving any other investigational agents or patients that have received
             other investigational agents within 14 days of enrollment

          -  Patients with history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to decitabine that are not easily managed

          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements; as infection is a common feature of AML, patients with active infection
             are permitted to enroll provided that the infection is under control

          -  Patients with serious medical or psychiatric illness likely to interfere with
             participation in this clinical study

          -  Pregnant women or women who are breastfeeding are excluded from this study;
             confirmation that the subject is not pregnant must be established by a negative serum
             B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during
             screening; pregnancy testing is not required for post-menopausal or surgically
             sterilized women

          -  Patients with metastatic malignant solid tumors who received treatment in the past 6
             months are excluded

          -  DONOR: Pregnancy

          -  DONOR: HIV
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Sumithira Vasu, MBBS, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02316964

Organization ID

OSU-14040

Secondary IDs

NCI-2014-01489

Responsible Party

Sponsor-Investigator

Study Sponsor

Sumithira Vasu


Study Sponsor

Sumithira Vasu, MBBS, Principal Investigator, Ohio State University Comprehensive Cancer Center


Verification Date

March 2020