Clinical trial NCT03420963: Donor Natural Killer Cells, Cyclophosphamide, and Etoposide in Treating Children and Young Adults With Relapsed or Refractory Solid Tumors
Official title: Ex-Vivo Expanded Allogeneic NK Cells for the Treatment of Solid Tumors of Pediatric Origin in Children and Young Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Recurrent Cutaneous Melanoma
Recurrent Lip and Oral Cavity Carcinoma
Recurrent Malignant Endocrine Neoplasm
Recurrent Malignant Female Reproductive System Neoplasm
Recurrent Malignant Male Reproductive System Neoplasm
Recurrent Malignant Mesothelioma
Recurrent Malignant Neoplasm of Multiple Primary Sites
Recurrent Malignant Oral Neoplasm
Recurrent Malignant Pharyngeal Neoplasm
Recurrent Malignant Skin Neoplasm
Recurrent Malignant Soft Tissue Neoplasm
Recurrent Malignant Solid Neoplasm
Recurrent Malignant Thyroid Gland Neoplasm
Recurrent Malignant Urinary System Neoplasm
Refractory Cutaneous Melanoma
Refractory Malignant Bone Neoplasm
Refractory Malignant Endocrine Neoplasm
Refractory Malignant Female Reproductive System Neoplasm
Refractory Malignant Male Reproductive System Neoplasm
Refractory Malignant Mesothelioma
Refractory Malignant Neoplasm of Multiple Primary Sites
Refractory Malignant Oral Neoplasm
Refractory Malignant Pharyngeal Neoplasm
Refractory Malignant Skin Neoplasm
Refractory Malignant Soft Tissue Neoplasm
Refractory Malignant Solid Neoplasm
Refractory Malignant Thyroid Gland Neoplasm
Refractory Malignant Urinary System Neoplasm
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-02-05
Enrollment: 38
Sex: ALL
Minimum age (years): 12
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVE:

I. Determine the safety, maximum tolerated dose and/or recommended phase II dose of cord blood-derived expanded allogeneic natural killer cells (expanded allogeneic cord donor natural killer \[NK\] cells) following chemotherapy.

SECONDARY OBJECTIVES:

I. Determine the persistence of adoptively-transferred cord NK cells after solid tumor directed chemotherapy.

II. Preliminarily define the antitumor activity to adoptively transferred NK cells following the study preparative regimen in the confines of a phase I study.

III. Determine the immunophenotype and function of the infused NK cell product. IV. Preliminarily evaluate for any correlate of phenotype, killer cell immunoglobulin-like receptor (kir) haplotype, and function with overall response.

OUTLINE: This is a dose escalation study of cord blood derived allogeneic NK cells.

Patients receive cyclophosphamide intravenously (IV) once daily (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.

After completion of study treatment, patients are followed up at 3-4 days, and then every week for 30 days.

Eligibility criteria: Inclusion Criteria:

* 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):

    * 1 month to \< 6 months, male 0.4, female 0.4;
    * 6 months to \< 1 year, male 0.5, female 0.5;
    * 1 to \< 2 years, male 0.6, female 0.6;
    * 2 to \< 6 years, male 0.8, female 0.8;
    * 6 to \< 10 years, male 1, female 1;
    * 10 to \< 13 years, male 1.2, female 1.2;
    * 13 to \< 16 years, male 1.5, female 1.4;
    * \>= 16 years, male 1.7, female 1.4.
* ENROLLMENT: Adequate liver function, defined as: total bilirubin =\< 2 mg/dl
* ENROLLMENT: Adequate liver function, as defined as serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x upper limit of normal (ULN) for age (unless Gilbert's disease or abnormal liver function due to primary disease).
* ENROLLMENT: Evidence of adequate bone marrow function (defined by absolute neutrophil count \>= 750), unless patient has documented tumor metastasis to the bone marrow or other condition that results in cytopenia without abnormal marrow function.
* ENROLLMENT: Evidence of adequate bone marrow function (defined by platelets \>= 50,000), unless patient has documented tumor metastasis to the bone marrow or other condition that results in cytopenia without abnormal marrow function.
* ENROLLMENT: Pulmonary symptoms controlled by medication and pulse oximetry \>= 92% on room air.
* ENROLLMENT: Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the investigator. (Non-childbearing potential defined as pre-menarche, greater than one year post-menopausal or surgically sterilized).
* ENROLLMENT: Confirmation that a cord blood donor which is matched with the recipient at a 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and HLA class II (molecular) antigens.
* ENROLLMENT: Signed informed consent and if applicable pediatric assent.

Exclusion Criteria:

* SCREENING: Primary tumors of the central nervous system.
* SCREENING: Chronic corticosteroid dependence that is unable to be weaned to discontinue.
* SCREENING: Determined by study doctor that patient is unlikely to meet inclusion criteria after screening.
* 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.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 30 days after the NK cell infusion
measure: Maximum tolerated dose and/or recommended phase 2 dose of cord blood-derived expanded allogeneic natural killer (NK) cells following chemotherapy
timeFrame: Up to 30 days after the NK cell infusion
Secondary outcomes:
measure: Response rate per immune-related therapy trials Response Evaluation Criteria in Solid Tumors (irRECIST)
timeFrame: Up to 30 days after the NK cell infusion
measure: NK cell persistence, phenotype, and function
timeFrame: Up to 30 days after the NK cell infusion
measure: Overall survival (OS)
timeFrame: Up to 30 days after the NK cell infusion
measure: Time to progression (TTP)
timeFrame: Up to 30 days after the NK cell infusion
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Demetrios Petropoulos
role: PRINCIPAL_INVESTIGATOR
References: