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Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.

Lab test in which leukemia cells obtained from blood or bone marrow are tested for sensitivity to 115 drugs individually and in certain combinations

Chemosensitivity Assay

Cytology Specimen Collection Procedure

Analysis of leukemia cell genes to identify possible drug targets

Gene Expression Analysis

Genetic Variation Analysis

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

In Vitro Sensitivity-Directed Chemotherapy

Mary-Elizabeth Percival

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.

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

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%.

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)

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.

National Cancer Institute (NCI)

University of Washington

Assistant Professor, Division of Hematology

Non-hematologic toxicities \>/= grade 3 were recorded from time of assay-guided therapy administration through 14 days after last administration of study therapy Hospitalizations or prolongation of hospitalizations for protocol-scheduled procedures, blood product transfusions, or for social reasons (i.e. awaiting transport home) were not considered SAEs. And hospitalization or prolongation of hospitalizations for fever and/or infection were considered expected, and not considered SAEs.

Leukemia cells purified from blood or bone marrow samples are analyzed for sensitivity to individual drugs and drug combination and by next generation sequencing.

Chemosensitivity Assay: Lab test in which leukemia cells obtained from blood or bone marrow are tested for sensitivity to 115 drugs individually and in certain combinations

Cytology Specimen Collection Procedure: Undergo blood or bone marrow collection

Gene Expression Analysis: Analysis of leukemia cell genes to identify possible drug targets

Genetic Variation Analysis: Analysis of leukemia cell genes to identify possible drug targets

In Vitro Sensitivity-Directed Chemotherapy: 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

Chemosensitivity Testing

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Percival

Chemosensitivity Testing and Treatment Initiation Within 21 Days

Percentage of Patients we Are Able to Test and Initiate Treatment Within a 21 Day Period

Treatment (Chemosensitivity Testing, Chemotherapy)

Number of complete remissions + complete remissions with incomplete blood counts

Rate of Complete Remission

Overall survival in months from date of study consent

Survival

Overall Study

Spots Global Cancer Trial Database for genetic variation analysis