Specialized Stem Cell Transplant Product (Hematopoietic Progenitor Blood Cell Graft Cells) for the Treatment of Children, Adolescent and Young Adult Patients with Hematologic Cancers

Inclusion Criteria

• PATIENTS: Children, adolescents, young adults (age 6 months to =< 39 years) with malignant hematological diseases: * Acute lymphoblastic leukemia (ALL): ** ALL high risk including one or more of the following: (t(9;22) or 11q23 chromosomal abnormality, primary induction failure [=< 15% blasts at time of registration], mixed phenotype acute leukemia [MPAL], persistent minimal residual disease [MRD] [>= 0.01% by flow or persistent abnormal karyotype detected by cytogenetics] or hypodiploidy [=< 44 chromosomes]) in first remission*** ** ALL in second remission and beyond *** Complete remission (CR) is defined as < 5% blasts by morphology and flow cytometry on the pre-transplant bone marrow evaluation with minimum sustained absolute neutrophil count (ANC) of 300 cells/microliter for 1 week or ANC > 500 cells/microliter * Acute myeloid leukemia (AML) ** History of AML induction/reinduction failure (=< 15% blasts at time of registration) ** AML in complete remission 1 (CR1) with poor cytogenetics (i.e., 12p, 5a, -7, FLT3 mutation/duplication, t(9;11) and others) ** AML with persistent minimal residual disease (MRD) in CR1 (>= 0.01% on flow or persistent abnormal karyotype detected by cytogenetics) ** AML complete remission 2 (CR2) or beyond ** AML in refractory relapse but =< 15% bone marrow leukemia blasts ** Therapy-related AML * Juvenile myelomonocytic leukemia (JMML) ** JMML in CR1 without CBL mutation ** JMML with recurrence of disease with or without CBL mutation ** JMML CR2 or beyond * Chronic myeloid leukemia (CML) ** CML in complete remission (CR) with regard to blast crisis * High risk myelodysplastic syndrome (MDS) * Lymphoma: Hodgkin (HL) or non-Hodgkin (NHL) ** HL or NHL with a history of induction failure ** HL or NHL in partial remission 1 (PR1) or partial remission 2 (PR2) ** HL or NHL in CR2 or subsequent remission
• PATIENTS: 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)
• PATIENTS: Human leukocyte antigen (HLA)-matched (5-6/6) sibling donor, matched (8-10/10) unrelated donor available for stem cell donation, haplo-identical related donor (at least one full haplotype must be matched)
• PATIENTS: 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
• PATIENTS: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and corrected diffusing capacity of the lungs for carbon monoxide (DLCO) must all be ≥ 60% 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)
• PATIENTS: 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 (male 0.6 mg/dL; female 0.6 mg/dL) * Age 2 to < 6 years: Maximum serum creatinine (male 0.8 mg/dL; female 0.8 mg/dL) * Age 6 to < 10 years: Maximum serum creatinine (male 1 mg/dL; female 1 mg/dL) * Age 10 to < 13 years: Maximum serum creatinine (male 1.2 mg/dL; female 1.2 mg/dL) * Age 13 to < 16 years: Maximum serum creatinine (male 1.5 mg/dL; female 1.4 mg/dL) * Age 16 years and up: Maximum serum creatinine (male 1.7 mg/dL; female 1.4 mg/dL)
• PATIENTS: Shortening fraction of ≥ 27% by echocardiogram or ejection fraction of ≥ 50% by echocardiogram or radionuclide scan (multigated acquisition scan [MUGA]) (within 4 weeks of initiation of preparative regimen)
• PATIENTS: Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) < 5 x upper limit of normal (ULN) for age (within 4 weeks of initiation of preparative regimen)
• PATIENTS: Conjugated bilirubin < 2.5 mg/dL, unless attributable to Gilbert’s syndrome (within 4 weeks of initiation of preparative regimen)
• PATIENTS: Written informed consent obtained from the subject or guardian and the subject agrees to comply with all the study-related procedures
• PATIENTS: Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 8 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. SOCBP includes any woman 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 subjects with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL
• PATIENTS: Subjects with 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 8 weeks following the last dose of study drug
• DONORS: Donors may be matched sibling donors, matched unrelated donors, or first generation haploidentical relative (at least one full haplotype must be matched)
• DONORS: 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: Donors will undergo infectious disease screening per institutional standard operating procedure (SOP) within 30 days of collection. (Minimum infectious testing will be screened and tested 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 CMV.)
• DONORS: Absolute neutrophil count ≥ 1000/m^3
• DONORS: Hemoglobin ≥ 9 g/dL
• DONORS: Platelet count ≥ 50,000/mm^3
• DONORS: Rest of eligibility based on institutional standards

Exclusion Criteria

• PATIENTS: Patients with documented uncontrolled infection
• PATIENTS: Patients who have received allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months, unless being done as a boost
• PATIENTS: Patients with active ≥ grade 2 aGVHD
• PATIENTS: Demonstrated lack of compliance with medical care
• PATIENTS: 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 8 weeks after the last dose of study drug
• PATIENTS: Females who are known to be pregnant or breastfeeding
• PATIENTS: 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
• PATIENTS: Prisoners or subjects who are incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness