Validation of an in Vitro Assay to Predict Targeted Therapies for Acute Leukemia Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Bristol-Myers Squibb
Information provided by (Responsible Party):
OHSU Knight Cancer Institute Identifier:
First received: June 13, 2012
Last updated: October 14, 2015
Last verified: October 2015

June 13, 2012
October 14, 2015
June 2012
March 2017   (final data collection date for primary outcome measure)
Bone marrow blast percentage [ Time Frame: 28 days after treatment ] [ Designated as safety issue: No ]
Clinical activity will be defined as > 25% decrease in bone marrow blast counts at any evaluable time in the 28 day treatment window.
Bone marrow blast percentage [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01620216 on Archive Site
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Validation of an in Vitro Assay to Predict Targeted Therapies for Acute Leukemia Patients
A Phase II Pilot Study of Kinase Inhibition in Relapsed/Refractory Acute Leukemias: Using a Comprehensive in Vitro Kinase Inhibitor Panel to Select Individualized, Targeted Therapies.
Patients with relapsed or refractory acute leukemias, including acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), have a dismal prognosis with conventional chemotherapy. The development of more effective and less toxic therapies will require the identification of the molecular abnormalities contributing to leukemogenesis and the identification of drugs that specifically block the activity of these lesions. The investigators hypothesize that aberrantly activated tyrosine kinase signaling pathways play a critical role in the pathogenesis of acute leukemia, and effective therapies will need to be determined on an individual patient basis. To address this need, the investigators have developed a small-molecule kinase inhibitor assay that can identify therapeutic targets in tyrosine kinase signaling pathways in primary acute leukemia samples and provide individualized therapeutic options. The goals of this project are to validate the role of a pre-clinical kinase inhibitor screen in predicting effective individualized therapies and to explore the molecular abnormalities underlying drug sensitivity. Accordingly, the first aim is to evaluate the efficacy of an in-vitro inhibitor sensitivity assay for prediction of clinically effective individualized/targeted therapies for acute leukemia patients in a single-arm phase II pilot trial enrolling 24 patients. Inclusion criteria will be limited to relapsed/refractory acute leukemia patients with in vitro sensitivity to one or more drugs in the inhibitor assay. The primary objective is to determine the clinical activity, defined as >25% decrease in bone marrow blast counts at 28 days after initiation of therapy. The second aim is to identify the genetic etiology underlying aberrantly activated tyrosine kinase pathways in leukemia samples from individual patients. The mechanism of activation will be explored using high-throughput sequence and expression profiling. By utilizing the investigators' pre-clinical assay to select individualized leukemia therapies, the investigators hope to create a platform upon which they can rapidly test the effectiveness of individualized kinase therapy and apply this information to enhance development of new drugs and new drug combinations in leukemia patients. It is also the investigators' hope to establish a paradigm in which patient-tailored therapies can be offered to all patients with cancer.
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Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia
  • Device: in vitro kinase inhibitor assay
    An in vitro kinase inhibitor assay will be used to determine the sensitivity of primary leukemic cells to four kinase inhibitors/drugs.
  • Drug: Sunitinib
    50 milligrams (mg) orally once daily, with or without food, 4 weeks on treatment
  • Drug: Dasatinib
    100 mg once daily with possible escalation to 140 mg once daily for 28 days
  • Drug: Nilotinib
    400 mg twice daily for 28 days
  • Drug: Sorafenib
    400 mg (2 tablets) orally twice daily without food for 28 days
  • Drug: Ponatinib
    45 mg dose once per day
Experimental: Treatment
Patients treated with targeted kinase inhibitor selected by in vitro assay
  • Device: in vitro kinase inhibitor assay
  • Drug: Sunitinib
  • Drug: Dasatinib
  • Drug: Nilotinib
  • Drug: Sorafenib
  • Drug: Ponatinib
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
March 2017
March 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with relapsed/refractory leukemia with a confirmed diagnosis of acute myelogenous leukemia or acute lymphoblastic leukemia who have in vitro kinase inhibitor sensitivity as determined by our functional kinase inhibitor screen
  • Patients have relapsed and are refractory to at least 1 cycle of salvage therapy
  • Patients have not received leukemia treatment within 2 weeks of starting study drug
  • Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
  • Patients must have normal organ function as defined by protocol
  • Normal corrected QT (QTc) interval on screening electrocardiogram (ECG) evaluation
  • Discontinuation of any medications known to contribute significantly to the risk of QT prolongation up to 48 hours prior to start of study drug
  • Discontinuation of anti-coagulants and anti-platelet drugs up to 5 days prior to start of study drug
  • No uncontrolled infections as determined by the investigator
  • No uncontrolled thyroid disease
  • No active graft-versus-host disease (GVHD)
  • Must be able to take oral medication
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration
  • Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped. Women of childbearing potential and men with a significant other of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy
  • Ability to understand and the willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) document

Exclusion Criteria:

  • Patients may not receive concurrent chemotherapy, radiotherapy or immunotherapy, nor have received any other investigational agents within the last 14 days of start of screening
  • Patients may not have pleural or pericardial effusion of any grade
  • Known pulmonary arterial hypertension (dasatinib subjects only)
  • Uncontrolled angina, greater than New York Heart Association (NYHA) class III congestive heart failure or myocardial infarction within 6 months prior to study enrollment
  • Diagnosed congenital long QT syndrome
  • Any history of clinically significant ventricular arrhythmias
  • Subjects with hypokalemia or hypomagnesemia that cannot be corrected prior to kinase inhibitor administration
  • History of significant bleeding disorder unrelated to cancer.
  • Concomitant medications that are generally accepted to have a risk of causing Torsades de Pointes.
  • Drugs that affect the Cytochrome P450 3A4 (CYP3A4) system (inducers/inhibitors/substrates) are allowed but should be used with caution depending on specific kinase inhibitor used.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or lactating women are excluded from this study because of possible risk to the fetus or infant
  • Known Human immunodeficiency virus (HIV) positive patients are excluded from the study because of possible risk of lethal infection when treated with marrow suppressive therapy.
21 Years to 70 Years   (Adult, Senior)
Contact: Marc M Loriaux, MD, PhD 503-494-9893
Contact: Stephen Spurgeon, MD 503-494-8950
United States
7195, 1R21CA159265-01
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OHSU Knight Cancer Institute
OHSU Knight Cancer Institute
  • National Cancer Institute (NCI)
  • Bristol-Myers Squibb
Principal Investigator: Marc M Loriaux, MD, PhD Oregon Health and Science University
Principal Investigator: Stephen Spurgeon, MD Oregon Health and Science University
OHSU Knight Cancer Institute
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP