Orca Q Stem Cells for the Treatment of Pediatric Patients with Leukemia

Inclusion Criteria

• DONOR: Age ≥ 18 and ≤ 50 years at time of enrollment
• DONOR: Match to the patient as follows: * Matched related donor who is a 7 or 8/8 match for human leukocyte antigen (HLA) -A, -B, -C, and -DRB1, all typed using deoxyribonucleic acid (DNA) -based high resolution methods * Matched unrelated donor who is a 7 or 8/8 match at HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods * Haploidentical related donor who is a ≥ 4/8 but < 7/8 match at HLA-A, -B, -C, and -DRB1 (typed using DNA-based high-resolution methods), with at most one mismatch per locus
• DONOR: Willing to donate peripheral blood stem cells (PBSC) for up to two consecutive days
• DONOR: Able to donate within North America or Hawaii at a site that will employ a Spectra Optia Apheresis System for post-mobilization apheresis
• DONOR: Meets federal eligibility criteria for donors of viable, leukocyte-rich cells or tissues as defined by 21 Code of Federal Regulations (CFR) section 1271 2018 and all relevant Food and Drug Administration (FDA) Guidance for Industry
• DONOR: Donors determined to be ineligible, based on the results of required testing and/or screening, may nonetheless be included if either apply, as per 21 CFR section 1271.65 2018: * The donor is a first-degree or second-degree blood relative of the recipient * Urgent medical need, meaning no comparable human cell product is available and the recipient is likely to suffer death or serious morbidity without the human cell product, as attested by the investigator
• DONOR: Meets any other criteria for donation as specified by standard National Marrow Donor Program (NMDP) guidelines (NMDP donors) or institutional/ Foundation for the Accreditation of Cellular Therapy (FACT) standards (non-NMDP donors)
• RECIPIENT: Age < 22 years of age at the time of diagnosis of malignancy
• RECIPIENT: Eligible for treatment at a pediatric HCT center
• RECIPIENT: Patients with the following histopathologically-confirmed diseases: * Acute myeloid, lymphoid, mixed phenotype or undifferentiated leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) as defined by: ** Marrow blasts < 5% by morphologic examination ** Absolute neutrophil count > 1.0 x 10^9 /L ** Platelet count > 100 x 10^9 /L ** Absence of leukemic blasts in the peripheral blood by morphological examination, and ** No evidence of extramedullary disease ** CRi: all CR criteria except for residual neutropenia (< 1.0 × 10^9/L) or thrombocytopenia (< 100 × 10^9/L) * Myeloid or lymphoid blast crisis or accelerated phase developing in the setting of chronic myeloid leukemia is an allowed diagnosis provided that patients are in CR or CRi with regard to the blast crisis
• RECIPIENT: Planned to undergo myeloablative (MA)-alloHCT with a myeloablative conditioning regimen
• RECIPIENT: Available donor willing to donate PBSCs: * Related donor who is a 7 or 8/8 match for HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods * Matched unrelated donor who is a 7 or 8/8 match at HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods * Haploidentical related donor who is a ≥ 4/8 but < 7/8 match at HLA-A, -B, -C, and -DRB1 (typed using DNA-based high-resolution methods), with at most one mismatch per locus
• RECIPIENT: Serum creatinine within normal range for age and estimated glomerular filtration rate (GFR) by Schwartz equation > 70 ml/min/1.73m^2. If serum creatinine is higher than normal, obtain creatinine clearance or nuclear medicine glomerular filtration rate. GFR of ≥ 70 mL/minute/1.73m^2 is required
• RECIPIENT: Cardiac ejection fraction at rest ≥ 50% by echocardiogram or radionuclide scan (MUGA)
• RECIPIENT: Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 70% or pulse oximetry (ox) on room air (RA) > 95% for patients who cannot cooperate with the pulmonary function test (PFTs)
• RECIPIENT: Total bilirubin < 1.5 times upper limit of normal (ULN) (< 3 times if attributed to Gilbert’s syndrome)
• RECIPIENT: Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) < 4 times ULN
• RECIPIENT: Recipients in screening must screen negative for SARS-CoV-2 ribonucleic acid (RNA) using a polymerase chain reaction (PCR)-based test prior to enrollment as follows: * The SARS-CoV-2 testing screening test should be timed such that the results are available prior to the start of the recipient’s conditioning regimen. Efforts should be made to minimize the window of time between test result availability and the start of conditioning. * Recipients in screening who test positive for SARS-CoV-2 are ineligible but may be considered eligible for future trial participation provided that they are cleared for transplantation per the most current American Society for Transplantation and Cellular Therapy (ASTCT) guidelines
• RECIPIENT: 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)
• RECIPIENT: Written informed consent obtained from the subject or parental/legal representative permission and subject’s assent, if applicable, stating that the subject agrees to comply with all the study-related procedures
• RECIPIENT: Women of childbearing potential (WOCBP) 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, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. WOCBP 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 women 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.
• RECIPIENT: Males 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 after transplantation

Exclusion Criteria

• DONOR: Evidence of active infection
• DONOR: Seropositive for human immunodeficiency virus (HIV)-1 or -2, human T-cell lymphotropic virus (HTLV) -1 or -2
• DONOR: Positive for active or chronic hepatitis B (hepatitis B virus [HBV]) based on serology [HBV surface antigen (HBsAg), total anti-Hepatitis B core antibody (HBcAb, IgG and IgM), and hepatitis B surface antibody (HBsAb)] or by nucleic acid testing (NAT). Donors with ambiguous HBV serology results should be tested for HBV by NAT
• DONOR: Positive for anti-hepatitis C (hepatitis C virus [HCV]) antibody or HCV NAT
• DONOR: Potential for Zika virus infection as defined as any of the following: * Medical diagnosis of Zika virus infection in the past 6 months * Residence in, or travel to, an area with active Zika virus transmission within the past 6 months * Sex within the past 6 months with a person who is known to have either of the risk factors listed above * Donors determined to be ineligible based on the results of Zika virus screening may be determined to be eligible if: ** The donor has no signs or symptoms consistent with active Zika virus infection and either of the following is true: *** The donor is a first-degree or second-degree blood relative of the recipient *** Urgent medical need, meaning no comparable human cell product is available and the recipient is likely to suffer death or serious morbidity without the human cell product, as attested by the investigator
• DONOR: Aberrant CD45RA isoform expression by central laboratory testing
• DONOR: Women who are pregnant or breastfeeding and unwilling to cease breastfeeding
• RECIPIENT: Prior myeloablative allogeneic HCT
• RECIPIENT: Currently receiving corticosteroids or other immunosuppressive therapy (topical corticosteroids or physiologic replacement hydrocortisone is allowed)
• RECIPIENT: Planned donor lymphocyte infusion (DLI)
• RECIPIENT: Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab. Anti-thymocyte globulin is allowed only as specified in the protocol
• RECIPIENT: Positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either: * A positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing), or * The presence of anti-donor HLA antibody to any of the following HLA loci: HLA-A, -B, -C, –DRB1, -DQB1, -DQA1, -DPB1, or -DPA1, with mean fluorescence intensity (MFI) > 1000 by solid phase immunoassay
• RECIPIENT: Lansky play scale < 70% or Karnofsky < 70%
• RECIPIENT: Hematopoietic cell transplantation specific Comorbidity Index (HCT-CI) > 4
• RECIPIENT: Documented or suspected bridging fibrosis or liver cirrhosis
• RECIPIENT: Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
• RECIPIENT: Seropositive for HIV-1 or -2, HTLV-1 or -2
• RECIPIENT: Known allergy or hypersensitivity to, or intolerance of, tacrolimus
• RECIPIENT: Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
• RECIPIENT: Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
• RECIPIENT: Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
• RECIPIENT: Females who are confirmed to be pregnant or breastfeeding and unwilling to cease breastfeeding
• RECIPIENTS: 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.
• RECIPIENT: Any serious medical condition or abnormality in clinical laboratory tests that, in the Investigator’s or treating physician’s judgement, precludes the recipient’s safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results
• RECIPIENT: Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment (conditioning regimen). Non-live versions of the COVID-19 vaccine are allowed
• RECIPIENT: Prisoners or subjects who are involuntarily incarcerated, wards of state, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness