NCT01787474

Brief 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). 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started May 2014

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 6, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 8, 2013

Completed
1.3 years until next milestone

Study Start

First participant enrolled

May 19, 2014

Completed
7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 17, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 17, 2021

Completed
Last Updated

June 21, 2021

Status Verified

June 1, 2021

Enrollment Period

7.1 years

First QC Date

February 6, 2013

Last Update Submit

June 18, 2021

Conditions

Recurrent Adult Acute Myeloid LeukemiaRefractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (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

    Day 28

Secondary Outcomes (3)

  • Complete remission rate (CR)

    Day 56 following infusion of the NK cells

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

    Up to day 56

  • Time to transplantation (TTT)

    Up to day 56

Study Arms (1)

Treatment (NK cells)

EXPERIMENTAL

Patients 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).

Drug: CytarabineBiological: FilgrastimBiological: Filgrastim-sndzDrug: Fludarabine PhosphateOther: Laboratory Biomarker AnalysisBiological: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

Interventions

CytarabineDRUG

Given IV

Also known as: .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, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Treatment (NK cells)
FilgrastimBIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim
Treatment (NK cells)
Filgrastim-sndzBIOLOGICAL

Given SC

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Zarxio
Treatment (NK cells)
Fludarabine PhosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Treatment (NK cells)
Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (NK cells)
Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer CellsBIOLOGICAL

Given IV

Also known as: (mbIL21)-expanded Haploidentical NK Cells, mbIL21-expanded Haploidentical NK Cells
Treatment (NK cells)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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)
  • +1 more criteria

You may not qualify if:

  • 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.)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CytarabineFilgrastimGranulocyte Colony-Stimulating Factorfludarabine phosphate

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

CytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Study Officials

  • Samer Srour, MBCHB

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 6, 2013

First Posted

February 8, 2013

Study Start

May 19, 2014

Primary Completion

June 17, 2021

Study Completion

June 17, 2021

Last Updated

June 21, 2021

Record last verified: 2021-06

Locations

US(1)