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

Individualized Treatment for Relapsed/Refractory Acute Leukemia Based on Chemosensitivity and Genomics/Gene Expression Data

This pilot clinical trial studies the feasibility of choosing treatment based on a high throughput ex vivo drug sensitivity assay in combination with mutation analysis for patients with acute leukemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). A high throughput screening assay tests many different drugs individually or in combination that kill leukemia cells in tiny chambers at the same time. High throughput drug sensitivity assay and mutation analysis may help guide the choice most effective for an individual's 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 OBJECTIVE:

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