Clinical Trial Finder

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 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.

Arms

Experimental: Treatment (cyclophosphamide, etoposide, NK cells)

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.

Interventions

Biological: - Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Given IV

Drug: - Cyclophosphamide

Given IV

Drug: - Etoposide

Given IV