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

Not Applicable

Completed

Conditions: Refractory Acute Lymphoblastic Leukemia
Recurrent Acute Leukemia of Ambiguous Lineage
Recurrent Acute Myeloid Leukemia
Recurrent Acute Lymphoblastic Leukemia
Refractory Acute Myeloid Leukemia
Refractory Acute Leukemia of Ambiguous Lineage

Interventions: Other: Chemosensitivity Assay
Other: Cytology Specimen Collection Procedure
Genetic: Gene Expression Analysis
Genetic: Genetic Variation Analysis
Drug: In Vitro Sensitivity-Directed Chemotherapy

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment (chemosensitivity testing, chemotherapy)	In Vitro Sensitivity-Directed Chemotherapy	Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.
Treatment (chemosensitivity testing, chemotherapy)	Gene Expression Analysis	Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.
Treatment (chemosensitivity testing, chemotherapy)	Chemosensitivity Assay	Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.
Treatment (chemosensitivity testing, chemotherapy)	Cytology Specimen Collection Procedure	Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.
Treatment (chemosensitivity testing, chemotherapy)	Genetic Variation Analysis	Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients we Are Able to Test and Initiate Treatment Within a 21 Day Period	Up to 21 days	The study will be considered successful (feasibility demonstrated) if it is possible to choose and initiate a combination drug regimen within 21 days in 9 out of 15 patients. With that outcome, there would be 90% confidence that the true feasibility rate is at least 40%.

Secondary Outcome Measures

Name	Time	Method
Rate of Complete Remission	Up to 2 years	The secondary objective is to evaluate the response to the chosen therapy. Response will be evaluated using European LeukemiaNet Response Evaluation Criteria in AML (2010 version)
Survival	Up to 2 years	Disease free and overall survival data will be assessed by contacting the referring MD or the patient every three months for the first two years.