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

Study Overview
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Brief Summary
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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
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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.

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

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

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemosensitivity testing, chemotherapy)<br>Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing. | Other: Chemosensitivity Assay<br>* Lab test in which leukemia cells obtained from blood or bone marrow are tested for sensitivity to 115 drugs individually and in certain combinations<br>* Other names: Chemosensitivity Testing;Other: Cytology Specimen Collection Procedure<br>* Undergo blood or bone marrow collection<br>* Other names: Cytologic Sampling;Genetic: Gene Expression Analysis<br>* Analysis of leukemia cell genes to identify possible drug targets<br>Genetic: Genetic Variation Analysis<br>* Analysis of leukemia cell genes to identify possible drug targets<br>* Other names: mutation analysis;Drug: In Vitro Sensitivity-Directed Chemotherapy<br>* Receive personalized chemotherapy with one or more of the following drugs: Afatinib Arsenic trioxide Axitinib Azacitidine Bexarotene Bortezomib Bosutinib Busulfan Cabazitaxel Cabozantinib Carfilzomib Ceritinib Cladribine Clofarabine Crizotinib Cytarabine HCl Dabrafenib Dasatinib Daunorubicin HCl Decitabine Erlotinib Etoposide Everolimus Fludarabine Gefitinib Gemcitabine HCl Hydroxyurea Imatinib Irinotecan Lapatinib Lomustine Melphalan Mercaptopurine Methotrexate Mitoxantrone Nelarabine Nilotinib Paclitaxel Pazopanib Pentostatin Ponatinib Pralatrexate Rapamycin Regorafenib Romidepsin Ruxolitinib Sorafenib Sunitinib Temsirolimus Thioguanine Topotecan HCl Trametinib Tretinoin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients we Are Able to Test and Initiate Treatment Within a 21 Day Period | 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%. | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Complete Remission | 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) | Up to 2 years | 
| Survival | 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. | Up to 2 years |