Last updated on April 2018

Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia


Brief description of study

This phase II trial studies how well targeted therapy works in treating patients with acute lymphoblastic leukemia or acute myelogenous leukemia that has come back after a period of improvement or does not respond to treatment. Testing patients' blood or bone marrow to find out if their type of cancer may be sensitive to a specific drug may help doctors choose more effective treatments. Dasatinib, nilotinib, sunitinib malate, sorafenib tosylate, and ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving targeted therapy based on cancer type may be an effective treatment for acute lymphoblastic leukemia or acute myelogenous leukemia.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To determine the clinical activity of kinase inhibitors using pre-clinical (in-vitro) activity to select individual therapy.

SECONDARY OBJECTIVES:

I. To evaluate overall objective response rates (complete response plus partial response).

II. Determine overall survival (OS) and progression-free survival (PFS). III. Any changes in transfusion requirements.

TERTIARY OBJECTIVES:

I. Prioritize active/aberrant kinase pathways using an in vitro inhibitor screen using individual primary leukemia samples.

II. Measure "on target" in vivo kinase inhibition and signal transducer and activator of transcription (STAT)-5 phosphorylation and correlate with response to treatment.

III. Perform next generation sequencing (whole exome sequencing) for complete mutational analysis.

IV. Identify aberrant gene expression in primary leukemia samples from study subjects.

V. Evaluate pharmacokinetics for each individual kinase inhibitor during therapy.

OUTLINE: Patients are assigned to 1 of 5 treatment groups based on pre-clinical kinase inhibitor activity.

GROUP I: Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive nilotinib PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

GROUP III: Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

GROUP IV: Patients receive sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

GROUP V: Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Clinical Study Identifier: NCT01620216

Contact Investigators or Research Sites near you

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Christopher S. Hourigan

National Heart Lung and Blood Institute
Bethesda, MD United States
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Marc Loriaux

OHSU Knight Cancer Institute
Portland, OR United States
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Robert H. Collins

UT Southwestern/Simmons Cancer Center-Dallas
Dallas, TX United States
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Tibor J. Kovacsovics

Huntsman Cancer Institute/University of Utah
Salt Lake City, UT United States
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