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Recurrent Adult Acute Myeloid LeukemiaPhase 1NCT01787474

Donor Natural Killer Cells in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Cytarabine, Filgrastim and Filgrastim-sndz in people with Recurrent Adult Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center 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 phase I/II trial studies the side effects and best dose of donor natural kill cells and to see how well they work in treating patients with acute myeloid leukemia that does not respond to treatment (refractory) or has come back after a period of improvement (relapsed). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cytarabine, Filgrastim and Filgrastim-sndz
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
19 May 2014to 17 Jun 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 primary refractory AML; patients with relapsed AML after allogeneic stem cell transplantation, including those who have received donor lymphocyte infusions, are eligible if they have no active graft versus host disease (GVHD) and are off immunosuppression
  • Have a haploidentical family peripheral blood donor selected for best possible killer cell immunoglobulin-like receptor (KIR) reactivity; KIR typing will not be indicated if there is only one haploidentical donor; KIR typing is advised to be done if feasible and does not delay transplant
  • Karnofsky or Lansky performance scale (PS) greater or equal to 70
  • Serum creatinine =< 2 mg/dl or creatinine clearance greater or equal than 40 cc/min; creatinine for pediatric patients =< 2 mg/dl or =< 2 times upper limit of normal for age (whichever is less)
  • Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50% of expected, corrected for hemoglobin; for pediatric patients, if unable to perform pulmonary function tests (most children < 7 years of age), pulse oximetry >= 92% on room air by pulse oximetry
  • Total bilirubin =< 2 mg/dl or =< 2.5 x upper limit of normal (ULN) for age (unless Gilbert's syndrome)
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  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN for age
  • Left ventricular ejection fraction >= 40%; no uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
  • Negative serum test to rule out pregnancy within 2 weeks prior to registration 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
  • Negative serology for human immunodeficiency virus (HIV)
  • DONOR: Donor must be 16 years of age or older and weigh at least 110 pounds
  • DONOR: Donor must be a human leukocyte antigen (HLA)-haploidentical relative selected for best NK alloreactivity, defined as having a KIR gene present on the donor NK cells for which the relevant HLA haplotype (KIR ligand) is absent in the recipient and present in the donor or selected on the basis of activating KIR gene content
  • DONOR: Donor must meet standard institutional eligibility and donor certification criteria for therapeutic cell product donation
  • DONOR: Not be pregnant as defined by negative serum (beta human chorionic gonadotropin [beta HCG]) pregnancy test in females of childbearing potential (non-childbearing potential defined as premenarchal, previous surgical sterilization, or postmenopausal for > 12 months)
  • DONOR: Evaluation: history and physical examination; laboratory examinations: hematology, electrolytes, chemistry; infectious disease screening and serology; HLA typing; KIR typing will not be indicated if there is only one haploidentical donor; KIR typing is advised to be done if feasible and does not delay transplant

Who cannot join

  • Congestive heart failure < 6 months prior to screening
  • Unstable angina pectoris < 6 months prior to screening
  • Myocardial infarction < 6 months prior to screening
  • Uncontrolled infection, defined as an infection which has not resolved spontaneously or does not show evidence of significant resolution after initiating appropriate therapy, excluding chronic asymptomatic viral infections (e.g., human papillomavirus [HPV], BK virus, hepatitis C virus [HCV], etc.)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I/II Clinical Trial Testing the Safety and Feasibility of IL-21-Expanded Natural Killer Cells for the Induction of Relapsed/Refractory Acute Myeloid Leukemia

This phase I/II trial studies the side effects and best dose of donor natural kill cells and to see how well they work in treating patients with acute myeloid leukemia that does not respond to treatment (refractory) or has come back after a period of improvement (relapsed). Giving natural killer cells after high dose chemotherapy 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).

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety, feasibility, and maximum tolerated dose of membrane-bound interleukin 21 (mbIL21)-expanded haploidentical natural killer (NK) cells after induction chemotherapy with fludarabine (fludarabine phosphate), cytarabine, and filgrastim-sndz, Zarxio (filgrastim-sndz) (G-CSF) (FLAG).

SECONDARY OBJECTIVES:

  1. Determine the persistence of adoptively-transferred expanded NK cells. II. Determine the immunophenotype and function of expanded NK cells. III. Determine the overall response of acute myeloid leukemia (AML) to this regimen.

IV. Correlate NK cell persistence, phenotype, and function with overall response.

  1. Estimate the rate at which patients receiving this regimen are able to go to transplant.

OUTLINE: This is a phase I, dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells followed by a phase II study.

Patients receive filgrastim-sndz subcutaneously (SC) once daily (QD) beginning on day -7 and continuing until absolute neutrophil counts (ANC) are equal or over 1000. Patients also receive fludarabine phosphate intravenously (IV) over 30 minutes and approximately 4 hours later followed by cytarabine IV over 1 hour on days -6 to -2 (days -6 to -3 for patients over age 60). Beginning 2-7 days after the last dose of fludarabine phosphate and cytarabine, patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells IV over 30 minutes thrice weekly for 3 doses over 4 days (Monday-Thursday only).

After completion of study treatment, patients are followed up for 56 days.

Being tested
Cytarabine, Filgrastim, Filgrastim-sndz, Fludarabine Phosphate, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • FilgrastimBiological

    Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

    Given SC

  • Filgrastim-sndzBiological

    Also called Filgrastim Biosimilar Filgrastim-sndz, Zarxio

    Given SC

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer CellsBiological

    Also called (mbIL21)-expanded Haploidentical NK Cells, mbIL21-expanded Haploidentical NK Cells

    Given IV

Study groups in NCT01787474
Study groupRoleWhat they receive
Treatment (NK cells)ExperimentalPatients receive filgrastim-sndz SC QD beginning on day -7 and continuing until ANC are equal or over 1000. Patients also receive fludarabine phosphate IV over 30 minutes and approximately 4 hours later followed by cytarabine IV over 1 hour on days -6 to -2 (days -6 to -3 for patients over age 60). Beginning 2-7 days after the last dose of fludarabine phosphate and cytarabine, patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells IV over 30 minutes thrice weekly for 3 doses over 4 days (Monday-Thursday only).
Receives: Drug: Cytarabine; Biological: Filgrastim; Biological: Filgrastim-sndz; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

What is being measured

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

  1. Maximum tolerated dose of natural killer (NK) cells, defined as the highest dose level at which no more than 2 patients in a 6-patient cohort experience a dose limiting toxicity during treatment

    Measured: Day 28

Secondary outcomes (3)

  1. Complete remission rate (CR)

    Estimated with Kaplan-Meier estimator and tabulated with 95% confidence intervals. Cox proportional hazards regression will be used to model CR as a function of NK cell dose.

    Measured: Day 56 following infusion of the NK cells

  2. NK-cell numerical expansion in vivo defined as an absolute circulating donor-derived NK cell count that increases above the post-infusion level

    Proportion of patients with successful in vivo NK-cell expansion estimated with a 95% confidence interval.

    Measured: Up to day 56

  3. Time to transplantation (TTT)

    Estimated with Kaplan-Meier estimator and tabulated with 95% confidence intervals. Cox proportional hazards regression will be used to model TTT as a function of NK cell dose.

    Measured: Up to day 56

Timeline

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

  1. First posted8 Feb 2013 (estimated)
  2. Study start19 May 2014
  3. Primary completion17 Jun 2021
  4. Study completion17 Jun 2021

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01787474
Sponsor's protocol ID
2012-0079
Other IDs
NCI-2014-00883, NCI-2014-00841, 2012-0079
Status last verified
Jun 2021
First submitted
6 Feb 2013
Last updated
21 Jun 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytarabine, Filgrastim and Filgrastim-sndz in people with Recurrent Adult Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of natural killer (NK) cells, defined as the highest dose level at which no more than 2 patients in a 6-patient cohort experience a dose limiting toxicity during treatment (time frame: Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01787474.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2021; AzTrials last refreshed its copy on 6 Nov 2026.

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