Trial Evaluating MGTA-456 in Patients With High-Risk Malignancy

Age, Unit Cell Dose and HLA Match Criteria

- Subjects must be ≤55 years of age

- Subjects must weigh >11 kg

- Subjects must have a partially HLA matched UCB unit with a pre-cryopreserved TNC dose
>1.0 x 107 per kilogram recipient weight. HLA matching is initially based on a minimum
of 4 of 6 HLA-A and B (at low or intermediate resolution by molecular typing) and DRB1
(at high resolution by molecular typing).

Eligible Diseases:

- 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, eg. 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-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 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 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 (eg, 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) IPSS Int-2 or High risk (i.e. RAEB, RAEBt <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/PR that is
ineligible for an autologous transplant.

Organ Specific Inclusion Criteria

- Karnofsky score ≥70 (16 years and older), Lansky play score >50 (children 2-16 years,
or 'adequate' score for children <2 years, as detailed in Appendix II.

- Adequate organ function defined as:

- Renal: Serum creatinine within normal range for age, or if serum creatinine
outside normal range for age, then creatinine clearance >40 ml/min or GFR ≥70
mL/min/1.73 m2.normal for age

- Hepatic: Bilirubin <3x upper limit of normal (ULN) and AST, ALT and alkaline
phosphatase <5x ULN.

- Pulmonary function: DLCO, FEV1, FEC (diffusion capacity) >5030% of predicted
(corrected for hemoglobin); if unable to perform pulmonary function tests, then
O2 saturation >95% on room air.

- Cardiac: No uncontrolled arrhythmia and left ventricular ejection fraction at rest
must be >3545%.

- Available 'back-up' 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 >2 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 tostumomab (Bexxar),
as part of their salvage therapy.