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

NCT ID: NCT01787474

Last Updated: 2021-06-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-19

Study Completion Date

2021-06-17

Brief Summary

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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).

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Detailed Description

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PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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.

Conditions

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Recurrent Adult Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (NK cells)

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).

Group Type EXPERIMENTAL

Cytarabine

Intervention Type DRUG

Given IV

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Filgrastim-sndz

Intervention Type BIOLOGICAL

Given SC

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

Intervention Type BIOLOGICAL

Given IV

Interventions

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Cytarabine

Given IV

Intervention Type DRUG

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Filgrastim-sndz

Given SC

Intervention Type BIOLOGICAL

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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.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 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim Filgrastim Biosimilar Filgrastim-sndz Zarxio 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 (mbIL21)-expanded Haploidentical NK Cells mbIL21-expanded Haploidentical NK Cells

Eligibility Criteria

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Inclusion Criteria

* 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)
* 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

Exclusion Criteria

* 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.)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Samer Srour, MBCHB

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center Website

Other Identifiers

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NCI-2014-00883

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2014-00841

Identifier Type: -

Identifier Source: secondary_id

2012-0079

Identifier Type: OTHER

Identifier Source: secondary_id

2012-0079

Identifier Type: -

Identifier Source: org_study_id

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