Laboratory Expanded Umbilical Cord Blood Product (Spanlecortemlocel) in Treating Patients with High-Risk Blood Cancers

Inclusion Criteria

• Subjects must be ≤ 55 years of age.
• Subjects must weigh > 11 kg.
• Subjects must have a partially human leukocyte antigen (HLA) matched UCB unit with a pre-cryopreserved total nucleated cell (TNC) dose > 1.0 x 10^7 per kilogram recipient weight. HLA matching is initially based on a minimum of 5 of 8 HLA alleles at high resolution A, B, C, DRB1 typing; searches will be performed according to the current Magenta Cord Blood Search Algorithm.
• Acute myelogenous leukemia (AML) in morphological complete remission with: * Minimal residual disease (MRD) by flow cytometry, or * Intermediate to high risk leukemia in first (CR1) based on institutional criteria, e.g. not favorable risk AML which is defined as having one of the following: ** T(8,21) without cKIT mutation. ** Inv(16) or t(16;16) without cKIT mutation. ** Normal karyotype with mutated NPM1 but FLT3-internal tandem duplication (ITD) wild type. ** Normal karyotype with double mutated CEBPA. ** Acute promyelocytic leukemia (APL) in first molecular remission at the end of consolidation. * Any second or subsequent complete remission (CR), or * Secondary AML with prior malignancy that has been in remission for at least 12 months.
• Acute lymphocytic leukemia (ALL) at the following stages: * High risk first morphological, cytogenetic and molecular CR with: ** MRD by flow cytometry, or ** Diagnosis of Philadelphia chromosome (Ph)+ ALL, or ** MLL rearrangement at diagnosis with slow early response at Day 14, or ** Hypodiploidy (< 44 chromosomes or deoxyribonucleic acid [DNA] index < 0.81) at diagnosis, or. ** End of induction M3 bone marrow, or ** End of induction M2 with M2-3 at Day 42 * High risk second CR based on institutional criteria (e.g., for children, bone marrow relapse < 36 months from induction or T-lineage bone marrow relapse or very early isolated central nervous system (CNS) relapse < 6 months from diagnosis, or slow re-induction (stage M2-3 at day 28 after induction) regardless of length remission. All patients with MRD by flow cytometry. * Any third or subsequent CR.
• Secondary ALL.
• Biphenotypic/undifferentiated leukemia in morphological, cytogenetic and molecular CR.
• Chronic Myelogenous Leukemia (CML) in high risk first chronic phase (failure of two tyrosine kinase inhibitors [TKI] or TKI intolerance), accelerated phase or second chronic phase.
• Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e. refractory anemia with excess blasts [RAEB], RAEB in transformation [t] < 5% blasts) or other high risk features, including multiple cytopenias, high risk cytogenetics or lack of response to standard therapy.
• Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma that is chemotherapy sensitive and ineligible for an autologous transplant.
• Burkitt’s lymphoma in CR2 or subsequent CR.
• Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/partial remission (PR) that is ineligible for an autologous transplant.
• Karnofsky score >= 70 (16 years and older), Lansky play score >= 50 (children 2-16 years, or ‘adequate’ score for children < 2 years.
• Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then creatinine clearance > 40 ml/min or glomerular filtration rate (GFR) normal for age.
• Bilirubin < 3 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST) < 5 x ULN.
• Alanine aminotransferase (ALT) < 5 x ULN.
• Alkaline phosphatase < 5 x ULN.
• Diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), FEC (diffusion capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 95% on room air.
• No uncontrolled arrhythmia and left ventricular ejection fraction at rest must be > 45%.
• Available ‘back-up’ hematopoietic stem and progenitor cells (HSPC) graft (e.g., second UCB unit, haploidentical related donor).
• Females of child bearing potential and sexually active males must agree to use adequate birth control during study treatment.
• Voluntary written consent signed (adult or parental) before performance of any study-related procedure not part of normal medical care.

Exclusion Criteria

• Patients with a HLA matched sibling donor or a HLA matched unrelated donor who is available for marrow or peripheral blood stem cell collection at the desired time of transplant.
• Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy.
• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology.
• Active bacterial, viral or fungal infection (currently taking medication and persistence of clinical signs and symptoms) with a minimum of 4 weeks of anti-fungal treatment.
• Prior autologous or allogeneic transplant.
• Other active malignancy.
• Subjects > 3 years of age unable to receive TBI 1320 cGy due to extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation, or prior Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar), as part of their salvage therapy.