NCT01620216

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

A Phase II Proof-of-Concept Trial to Study Kinase Inhibition in Relapsed/Refractory Acute Leukemias: Using a Comprehensive In Vitro Kinase Inhibitor Panel to Select Individualized, Targeted Therapies

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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, sunitinib malate, sorafenib tosylate, ponatinib hydrochloride, pacritinib, ruxolitinib, and idelalisib 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 description

PRIMARY OBJECTIVE: 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). EXPLORATORY/CORRELATIVE 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 7 treatment groups based on pre-clinical kinase inhibitor activity. GROUP I: Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP II: Patients receive sutinib malate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP III: Patients receive sorafenib tosylate PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP IV: Patients receive ponatinib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP V: Patients receive pacritinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP VI: Patients receive ruxolitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP VII: Patients receive idelalisib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Chronic Myelomonocytic Leukemia
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
OTHER	Antitumor Drug Screening Assay	Undergo pre clinical kinase inhibitor activity screening
DRUG	Dasatinib	Given PO
DRUG	Idelalisib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Pacritinib	Given PO
OTHER	Pharmacological Study	Correlative studies
DRUG	Ponatinib	Given PO
DRUG	Ponatinib Hydrochloride	Given PO
DRUG	Ruxolitinib	Given PO
DRUG	Sorafenib	Given PO
DRUG	Sorafenib Tosylate	Given PO
DRUG	Sunitinib	Given PO
DRUG	Sunitinib Malate	Given PO

Timeline

• Start date: 2012-05-11
• Primary completion: 2017-04-25
• Completion: 2017-04-30
• First posted: 2012-06-15
• Last updated: 2021-11-04
• Results posted: 2021-10-04

Locations

1 site across 1 country: United States