High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

PRIMARY OBJECTIVES:

I. To test patient cells in a high throughput assay against individual drugs and drug
combinations within 21 days to enable optimal choice of drug combinations for therapy.

II. To test gene expression that reveals activation of druggable pathways or mutations in
genes that confer susceptibility to specific agents may also be considered in choice of
treatment.

SECONDARY OBJECTIVES:

I. To evaluate the response to the chosen therapy.

OUTLINE:

Leukemia cells obtained from blood or bone marrow are analyzed for sensitivity to both
individual drugs and drug combinations via high throughput chemotherapy sensitivity assay and
next generation sequencing assays. Doctors will then recommend chemotherapy regimens based on
the results.

After completion of the chemotherapy regimen, patients are followed up at 2-4 weeks for
response, and then every 3 months for 2 years for duration of response and survival.

Inclusion Criteria:

- Diagnosis of acute leukemia by World Health Organization (WHO) criteria (e.g.-acute
myeloid leukemia, acute lymphoblastic leukemia, acute leukemia of ambiguous origin)

- Either:

- Relapsed after or refractory to prior treatment with at least two regimens or
lines of treatment

- Prior failure of at least one regimen or line of treatment, with poor cytogenetic
or other risk factors, and ineligible for other clinical trials

- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3

- Expectation that we can obtain about 10 million blasts from blood and/or marrow (e.g.,
circulating blast count of 5,000 or greater or cellular marrow with greater than or
equal to 20% blasts)

- Bilirubin =< 1 .5 x upper limit of normal (ULN) unless elevation is thought to be due
to Gilbert's syndrome, hemolysis, or hepatic infiltration by the hematologic
malignancy

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2.5 x
ULN, unless elevation is thought to be due to hepatic infiltration by the hematologic
malignancy

- Alkaline phosphatase =< 2.5 x ULN, unless elevation is thought to be due to hepatic
infiltration by the hematologic malignancy

- Serum creatinine =< 2.0 mg/dL

- Informed consent

- Willing to use contraception when appropriate

- Expected survival is greater than 100 days

Exclusion Criteria:

- No other active cancer that requires systemic chemotherapy or radiation

- Active systemic fungal, bacterial, viral or other infection, unless disease is under
treatment with antimicrobials and considered controlled in the opinion of the
investigator

- Significant organ compromise that will increase risk of toxicity or mortality

- Pregnancy or lactation