NCT03420963

Brief Summary

This phase I trial studies the side effects and best dose of cord blood-derived expanded allogeneic natural killer cells (donor natural killer \[NK\] cells) and how well they work when given together with cyclophosphamide and etoposide in treating children and young adults with solid tumors that have come back (relapsed) or that do not respond to treatment (refractory). NK cells, white blood cells important to the immune system, are donated/collected from cord blood collected at birth from healthy babies and grown in the lab. Drugs used in chemotherapy, such as cyclophosphamide and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving NK cells together with cyclophosphamide and etoposide may work better in treating children and young adults with solid tumors.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2018

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

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

January 29, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 5, 2018

Completed
7 months until next milestone

Study Start

First participant enrolled

August 31, 2018

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 26, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 26, 2026

Completed
Last Updated

March 20, 2026

Status Verified

March 1, 2026

Enrollment Period

7.5 years

First QC Date

January 29, 2018

Last Update Submit

March 17, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • Incidence of adverse events

    Since toxicity is the primary outcome, patients with non-measurable disease (who are still evaluable) will be included in the analysis and in these cases standard methods for categorizing response of non-measurable disease will be used. Toxicity rate will be estimated separately by dose and cohort along with a 95% confidence interval. Adverse events will be tabulated for all the patients separately by dose levels.

    Up to 30 days after the NK cell infusion

  • Maximum tolerated dose and/or recommended phase 2 dose of cord blood-derived expanded allogeneic natural killer (NK) cells following chemotherapy

    Primary analyses in this phase I trial are descriptive and exploratory. Toxicity rate will be estimated separately by dose and cohort along with a 95% confidence interval. Adverse events will be tabulated for all the patients separately by dose levels.

    Up to 30 days after the NK cell infusion

Secondary Outcomes (4)

  • Response rate per immune-related therapy trials Response Evaluation Criteria in Solid Tumors (irRECIST)

    Up to 30 days after the NK cell infusion

  • NK cell persistence, phenotype, and function

    Up to 30 days after the NK cell infusion

  • Overall survival (OS)

    Up to 30 days after the NK cell infusion

  • Time to progression (TTP)

    Up to 30 days after the NK cell infusion

Study Arms (1)

Treatment (cyclophosphamide, etoposide, NK cells)

EXPERIMENTAL

Patients receive cyclophosphamide IV QD over 30 minutes and etoposide IV QD over 60 minutes on days 1-5 in the absence of unacceptable toxicity. Patients then receive cord blood derived allogeneic NK cells IV on day 8.

Biological: Cord Blood-derived Expanded Allogeneic Natural Killer CellsDrug: CyclophosphamideDrug: Etoposide

Interventions

Given IV

Also known as: Allogeneic CB-derived Ex vivo-expanded NK Cells, CB-derived Expanded Allogeneic NK Cells, UCB-derived Expanded Allogeneic NK Cells, Umbilical Cord Blood-derived Expanded Allogeneic Natural Killer Cells
Treatment (cyclophosphamide, etoposide, NK cells)

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Treatment (cyclophosphamide, etoposide, NK cells)

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16
Treatment (cyclophosphamide, etoposide, NK cells)

Eligibility Criteria

Age12 Months - 40 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • SCREENING: Patients with relapsed or refractory solid tumors and without known curative therapy or therapy proven to proven to prolong survival with acceptable quality of life.
  • SCREENING: Patients older than 21 years must have a solid tumor considered by study doctor to be of the childhood cancer type.
  • SCREENING: Performance level as measured by Karnofsky \>= 60% for patients \> 16 years of age or Lansky \>= 60% for patients =\< 16 years of age.
  • SCREENING: Documentation of measurable or evaluable non-measurable disease.
  • SCREENING: At least one documented histological verification of solid tumor diagnosis. Can be from original diagnosis or more recent.
  • ENROLLMENT: Patient must have fully recovered (i.e. returned to baseline) from the clinically significant acute treatment-related toxicities of all prior treatments prior to beginning treatment on this protocol with exceptions of cytopenias resulting from persistent disease, hearing loss and alopecia.
  • ENROLLMENT: Performance level as measured by Karnofsky \>= 60% for patients \> 16 years of age or Lansky \>= 60% for patients =\< 16 years of age.
  • ENROLLMENT: Creatinine clearance \>= 60 mL/min/1.73m\^2 (calculated by 24 hour \[h\] urine collection or nuclear glomerular filtration rate \[GFR\] scan if 24 h collection is not possible) or a serum creatinine based on age and gender as follows:
  • Age, maximum serum creatinine (mg/dL):
  • month to \< 6 months, male 0.4, female 0.4;
  • months to \< 1 year, male 0.5, female 0.5;
  • to \< 2 years, male 0.6, female 0.6;
  • to \< 6 years, male 0.8, female 0.8;
  • to \< 10 years, male 1, female 1;
  • to \< 13 years, male 1.2, female 1.2;
  • +10 more criteria

You may not qualify if:

  • SCREENING: Primary tumors of the central nervous system.
  • SCREENING: Chronic corticosteroid dependence that is unable to be weaned to discontinue.
  • ENROLLMENT: Uncontrolled arrhythmias or uncontrolled symptoms of cardiac disease noted by screening history and physical. Patients with known cardiac dysfunction should have an ejection fraction (EF) \> 40% documented by echocardiogram (ECHO).
  • ENROLLMENT: Patients where the burden of pulmonary metastasis, location, or bulkiness of disease may cause high morbidity if localized swelling such as causing uncontrolled symptoms, oxygen dependence, or location near a major bronchi as determined by investigator.
  • ENROLLMENT: Pregnant females.
  • ENROLLMENT: Any uncontrolled systemic infection.

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

MelanomaMouth NeoplasmsEndocrine Gland NeoplasmsMesothelioma, MalignantPharyngeal NeoplasmsSkin NeoplasmsSarcomaThyroid NeoplasmsUrologic NeoplasmsBone Neoplasms

Interventions

CyclophosphamideEtoposide

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasNeoplasms by SiteSkin DiseasesSkin and Connective Tissue DiseasesHead and Neck NeoplasmsMouth DiseasesStomatognathic DiseasesEndocrine System DiseasesMesotheliomaAdenomaNeoplasms, Glandular and EpithelialNeoplasms, MesothelialLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsPleural NeoplasmsLung DiseasesRespiratory Tract DiseasesOtorhinolaryngologic NeoplasmsPharyngeal DiseasesOtorhinolaryngologic DiseasesNeoplasms, Connective and Soft TissueThyroid DiseasesUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesUrologic DiseasesBone DiseasesMusculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesCarbohydrates

Study Officials

  • Demetrios Petropoulos

    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

January 29, 2018

First Posted

February 5, 2018

Study Start

August 31, 2018

Primary Completion

February 26, 2026

Study Completion

February 26, 2026

Last Updated

March 20, 2026

Record last verified: 2026-03

Locations