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Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 1NCT02316964

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

A Phase 1 study testing decitabine, natural killer cell therapy and aldesleukin in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Del(5q), run by Sumithira Vasu at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
decitabine, natural killer cell therapy and aldesleukin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
21 Apr 2015to 20 Dec 2019
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • Patients with metastatic malignant solid tumors who received treatment in the past 6 months are excluded
  • DONOR: Pregnancy
  • DONOR: HIV

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
decitabine, natural killer cell therapy, aldesleukin, laboratory biomarker analysis
Keywords
AML, acute myeloid leukemia, decitabine
Medical subject headings
Congenital Abnormalities, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • decitabineDrug

    Also called 5-aza-dCyd, 5AZA, DAC

    20 mg/m2 Given IV (intravenous) for 5 days over 60 minutes

  • natural killer cell therapyBiological

    Undergo infusion of allogeneic NK cells on day 0

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02316964
Study groupRoleWhat they receive
Treatment (decitabine, allogeneic NK cells, aldesleukin)ExperimentalPatients 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.
Receives: Drug: decitabine; Biological: natural killer cell therapy; Biological: aldesleukin; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days post NK infusion

  2. 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.

    Measured: Within 4 hours of infusion

Secondary outcomes (2)

  1. Therapeutic response of these combinations of agents in patients ORR

    Therapeutic response assessed using International Working Group criteria

    Measured: Up to 30 days post-treatment

  2. 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.

    Measured: Up to 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Dec 2014 (estimated)
  2. Study start21 Apr 2015
  3. Primary completion6 Dec 2017
  4. Study completion20 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02316964
Sponsor's protocol ID
OSU-14040
Other IDs
NCI-2014-01489
Status last verified
Mar 2020
First submitted
20 Aug 2014
Last updated
9 Mar 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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