Modified Donor Peripheral Blood Stem Cells in Combination with Zoledronic Acid for the Treatment of Pediatric, Adolescent, and Young Adult Patients with Relapsed or Refractory Solid Tumors

Inclusion Criteria

• RECIPIENT INCLUSION CRITERIA:
• Patients age 6 months to =< 25 years
• Relapsed/refractory solid tumor whom failed or deemed ineligible to receive autologous transplant or if autologous transplant did not offer > 20% chance of cure with the following diseases. Subjects should have received and be refractory to available standard of care (SOC) therapy specific to their cancer type. Their prior medical history and therapies will be reviewed by their treating physician prior to enrollment: * Neuroblastoma (high risk with relapsed or refractory disease), * Relapsed/refractory rhabdomyosarcoma, * Relapsed/refractory non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): synovial sarcoma, malignant peripheral nerve sheath tumors (MPNST), * High risk adult type NRSTS: clear cell sarcoma, alveolar soft part sarcoma, * Other high-risk extracranial solid tumors: desmoplastic small round cell tumors, chordoma, malignant rhabdoid tumor, epithelioid sarcoma, myoepithelial tumor * Relapsed/refractory bone tumors: osteosarcoma and Ewing sarcoma/primitive neuroectodermal tumor (PNET), or * Other high-risk solid tumors with < 10% expected survival with conventional treatment
• Subjects must not have more than one active malignancy at the time of enrollment. (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen [as determined by the treating physician and approved by the principal investigator (PI)] may be included.)
• Haplo-identical related donor (at least one full haplotype must be matched)
• Karnofsky or Lansky score >= 60% at the time of enrollment. Karnofsky scores must be used for patients > 16 years of age and Lansky scores for patients =< 16 years of age
• Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and corrected diffusion capacity of the lung for carbon monoxide (DLCO) must all be >= 50% of predicted by pulmonary function tests (PFTs). For children who are unable to perform for PFTs due to age, the criteria are: no evidence of dyspnea at rest and no need for supplemental oxygen (within 4 weeks of initiation of preparative regimen)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 4 weeks of initiation of preparative regimen): * Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male), 0.6 (female) * Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male), 0.8 (female) * Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1 (male), 1 (female) * Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male), 1.2 (female) * Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female) * Age: 16 years and up; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)
• Ejection fraction of >= 50% by echocardiogram or radionuclide scan (multigated acquisition scan [MUGA]) (within 4 weeks of initiation of preparative regimen)
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures
• Individuals of childbearing potential (IOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for one year following transplantation to minimize the risk of pregnancy. Prior to study enrollment, individuals of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factor for an unintentional pregnancy. IOCBP includes any individual who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: * Amenorrhea that has lasted for >= 12 consecutive months without another cause, or * For individuals with irregular menstrual periods who are taking hormone replacement therapy (HRT), or * Women with a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL
• Subjects with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for one year following stem cell transplantation
• DONOR INCLUSION CRITERIA:
• Donors must be first generation haploidentical relative (at least one full haplotype must be matched) < 65 years of age
• Human leukocyte antigen (HLA) typing will be done using high resolution at HLA-A, B, C, and DRB1 loci. Additional testing performed per institutional standard of care
• Donors will undergo infectious disease screening per institutional standard operating procedure (SOP) within 30 days of collection. (Minimum infectious testing will include testing for HIV-1 [antigen and nucleic acid], HIV-2, hepatitis B virus [HBV, nucleic acid and surface and core antigen], hepatitis C virus [HCV, antigen and nucleic acid], Treponema pallidum [syphilis], West Nile virus [WNV], Creutzfeldt-Jakob disease [CJD] [screening only], Zika virus [screening only], human T-lymphotropic virus types 1 and 2 [HTLV-1, HTLV-2] and cytomegalovirus [CMV].)
• Absolute neutrophil count >= 1000/m^3 (at the time of donor evaluation)
• Hemoglobin >= 9 g/dL (at the time of donor evaluation)
• Platelet count >= 100,000/mm^3 (at the time of donor evaluation)

Exclusion Criteria

• RECIPIENT EXCLUSION CRITERIA:
• Patients with documented uncontrolled infection at the time of study entry are not eligible * Uncontrolled infection is patient without treatment antimicrobials and/or demonstrating progression despite antimicrobials
• Demonstrated lack of compliance with medical care, as determined by the treating physician
• Patients who have received an allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months
• Patients who do not have an eligible allogeneic donor available
• Patients with a life expectancy < 3 months
• Patients not meeting inclusion criteria for organ function
• Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one year after transplantation
• Females who are known to be pregnant or breastfeeding
• History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness