Safety and Efficacy of Human Myeloid Progenitor Cells (CLT-008) During Chemotherapy for Acute Myeloid Leukemia

The prolonged period of severe neutropenia caused by induction chemotherapy for the treatment
of AML is associated with a nearly universal risk of febrile neutropenia. Standard supportive
care strategies include administration of prophylactic anti-bacterial and anti-fungal agents,
but serious breakthrough bacterial and fungal infections still occur. Granulocyte
colony-stimulating factor (G-CSF; filgrastim, Neupogen®) has been shown to shorten the
duration of severe neutropenia, fever, antibiotic use and hospitalization following induction
chemotherapy for AML. CLT-008, a human allogeneic myeloid progenitor cell product, is
intended to provide the cellular target for G-CSF to produce neutrophils during the period of
chemotherapy-induced bone marrow suppression when the patient's own progenitor cells may be
limited in responding to G-CSF. It is hypothesized that the production of allogeneic
neutrophils from CLT-008 will be sufficient to mitigate the infection-related consequences of
induction chemotherapy for AML.

Inclusion Criteria:

1. Acute myeloid leukemia arising de novo (per European LeukemiaNet)

2. Treated with any established chemotherapy regimen based on either:

1. 7+3: Standard-dose cytarabine 100-200 mg per meter squared continuous infusion
for 7 days with idarubicin 12 mg per meter squared or daunorubicin 45-90 mg per
meter squared for 3 days

2. High-dose cytarabine-based (HIDAC) chemotherapy administering a total cytarabine
dose of ≥ 4 g per meter squared alone or in combination with other anti-leukemic
agents (for example, anthracyclines, purine nucleoside inhibitors, etoposide,
etc.)

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening or by
the day chemotherapy is initiated

4. Adequate respiratory function with a room air oxygen saturation of at least 92%

5. Adequate cardiac function defined as an ejection fraction of at least 45%

6. Serum bilirubin ≤ 1.5 times the upper limits of normal. Subjects with a history of
Gilbert's syndrome may be enrolled if the total bilirubin is < 3 mg/dL with an
indirect bilirubin of > 1.5 mg/dL

7. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times
upper limits of normal prior to chemotherapy

8. Serum creatinine ≤ 2 times upper limits of normal or estimated glomerular filtration
rate ≥ 60 mL/min/1.73 meter squared per Modification of Diet in Renal Disease equation
(MDRD)

9. All subjects, except post-menopausal women, must be willing to utilize a highly
effective method of contraception throughout the study

10. Adequately informed of the nature and risks of the study with written informed consent

Exclusion Criteria:

1. Pregnant or breast feeding

2. Overt central nervous system manifestations of leukemia at diagnosis

3. Specifically diagnosed and uncontrolled fungal, bacterial, viral, or other infection
(e.g. confirmed sepsis, pneumonia, abscess, cellulitis, etc.) at the day chemotherapy
is initiated. "Uncontrolled" is defined as exhibiting ongoing signs and symptoms of
infection without improvement despite antimicrobial or other treatment.

4. AML subtype M3 (promyelocytic leukemia)

5. Previous chemotherapy for AML

6. History of or current human immunodeficiency virus (HIV) or hepatitis C virus
infection

7. History of or current clinically significant immunodeficiency

8. Known contraindication to receiving G-CSF

9. History of or current clinically significant alloimmunization to leukocyte antigens

10. Participation in another clinical study within 28 days of the day chemotherapy is
initiated, in which the study drug or device may influence hematopoiesis.
Co-enrollment in another study is allowed in cases where the investigational therapy
under study is a version of an acceptable chemotherapy regimen for this study per the
inclusion criteria.

11. Receiving any agent concurrently with CLT-008 infusion which inhibits cell division
(e.g., methotrexate or hydroxyurea)

12. Acute or chronic medical disorder that, in the opinion of the investigator or medical
monitor, may prevent the subject from completing participation in the study