Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01441882
Recruitment Status : Completed
First Posted : September 28, 2011
Results First Posted : February 15, 2018
Last Update Posted : February 15, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Stephen Spurgeon, OHSU Knight Cancer Institute

Brief Summary:
This phase II trial studies how well dasatinib works in treating patients with chronic lymphocytic leukemia (CLL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Refractory Chronic Lymphocytic Leukemia Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia Drug: Dasatinib Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 2

Detailed Description:


I. To estimate the biologic target activity of dasatinib in CLL patients found to have pre-treatment in vitro dasatinib cytotoxicity (as defined by a >= 50% decrease in absolute lymphocyte count and/or bone marrow CLL count and/or lymph node or spleen size).


I. To evaluate overall objective response rates per CLL National Cancer Institute (NCI) working group.

II. To determine drug safety and tolerability of dasatinib in patients with CLL.

III. To determine overall (OS) and progression-free survival (PFS).


I. To determine if v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC), Bruton agammaglobulinemia tyrosine kinase (BTK), or tec protein tyrosine kinase (TEC) family kinase inhibition correlates with clinical response.

II. To determine which prognostic subgroups (presence of >= 1 of the following: 11q or 17p deletion; cluster of differentiation [CD]38 or zeta-chain-associated protein kinase 70 [Zap 70] expression; unmutated immunoglobulin heavy chain [IgVH]) respond to dasatinib therapy.

III. To evaluate differences in baseline CLL gene expression between CLL samples that are sensitive or in-sensitive to dasatinib.

IV. To analyze changes in CLL gene expression after dasatinib treatment. V. To evaluate dasatinib pharmacokinetics. VI. To evaluate changes in type I receptor tyrosine kinase-like orphan receptor (ROR-1) expression with dasatinib treatment.

VII. To correlate response to pre-clinical IC50 in the presence/absence of HS-5 conditioned media.

VIII. To explore role of possible kinase mutations related to dasatinib response.

IX. To measure chemokines before and during treatment.


Patients receive dasatinib orally (PO) once daily (QD) during course 1 and if tolerated, twice daily (BID) in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity
Study Start Date : October 2011
Actual Primary Completion Date : July 12, 2016
Actual Study Completion Date : January 1, 2018

Arm Intervention/treatment
Experimental: Treatment (dasatinib)
Patients receive dasatinib PO QD during course 1 and if tolerated, BID in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies

Primary Outcome Measures :
  1. In Vitro Dasatinib Sensitivity in Predicting Clinical Activity [ Time Frame: 8 weeks ]
    Defined by a decrease in absolute lymphocyte count, as determined by peripheral blood complete blood count (CBC) with differential or by bone marrow examination of 50 % and/or a decrease of detectable total lymph node size or spleen size by 50% (either by clinical examination contrast enhanced computed tomography [CT]). Summarized using descriptive statistics (e.g., proportions for categorical variables, and mean/standard deviation for continuous variables).

Secondary Outcome Measures :
  1. Incidence of Adverse Events Assessed According to the NCI Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 2 years ]
    Adverse events will be tabulated and summarized according to key reporting criteria (i.e., grade or seriousness, unanticipated, treatment attribution).

  2. Objective Response [ Time Frame: Up to 2 years ]
    Proportion of patients achieving the endpoint along with its 95% exact binomial confidence interval will be presented.

  3. Overall Survival [ Time Frame: Up to 2 years ]
    Kaplan-Meier method will be used to estimate the survival curve.

  4. Progression-free Survival [ Time Frame: Up to 2 years ]
    Kaplan-Meier method will be used to estimate the survival curve.

  5. Target Response Rate [ Time Frame: Up to 2 years ]
    Proportion of patients achieving the endpoint along with its 95% exact binomial confidence interval will be presented.

Other Outcome Measures:
  1. Biomarker Analysis of SRC, TEC, or BTK Family Kinase Inhibition [ Time Frame: Up to 2 years ]
    Use of either t-test (normally distributed variables) or Wilcoxon rank sum test (non-normally distributed variables) to determine whether the mean of continuous biomarkers or patient factors (e.g., IC50 dasatinib cytotoxicity, SRC family kinase inhibition level, TEC family kinase inhibition level, disease risk such as the presence or absence of poor risk features as defined in the protocol) are significantly different between responders and non-responders.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal information
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • In vitro dasatinib sensitivity (IC 50 =< 50 nm per MTS assay)
  • Diagnosis of CLL and must meet one of the following:

    • Relapsed CLL in all patients who have failed at least one prior treatment, regardless of risk group
    • OR De novo (treatment-naïve) patients age >= 65 who are not candidates for or do not want to pursue aggressive chemotherapy treatment
  • Have indications for treatment or evidence of progressive disease defined as follows (1996 NCI working group):

    • Massive or progressive splenomegaly
    • Massive lymph nodes (>= 10 cm), nodal clusters (>= 10 cm), or progressive lymphadenopathy
    • Symptomatic anemia and/or thrombocytopenia (Rai stages III or IV disease)
    • Autoimmune hemolytic anemia and/or thrombocytopenia that are poorly responsive to corticosteroid therapy
    • Progressive lymphocytosis with increase in lymphocyte count of >= 50% over a 2-month period or an anticipated doubling time of < 6 months
    • Repeated episodes of infection
  • Have not received CLL treatment within the past 2 weeks
  • Total bilirubin < 2.0 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
  • Serum creatinine < 2.0 x ULN
  • International normalized ratio (INR) =< 1.2
  • Platelet (Plt) count > 30,000
  • Ability to take oral medication (dasatinib must be swallowed whole)
  • No clinically significant infections as determined by the investigator
  • Normal corrected QT (QTc) interval (< 450 msec)
  • Serum potassium and magnesium are within normal limits
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity =< 25 IU HCG/L) 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 prior to study enrollment; women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy
  • After consent, discontinuation ("washout period") of any medications known to contribute significantly to the risk of QT prolongation or interfere with cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) mediated drug metabolism
  • Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy (discontinue St. John's Wort at least 5 days before starting dasatinib)
  • Patient agrees that IV bisphosphonates will be withheld for the first eight weeks of dasatinib therapy due to risk of hypocalcemia
  • Patient agrees to discontinue anti-coagulants and anti-platelet drugs; note: a low dose aspirin regimen (81mg QD) is permitted with close monitoring of the subject's platelets for a level >= 50,000/mm^3

Exclusion Criteria:

  • Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy
  • Pleural or pericardial effusion of any grade
  • Uncontrolled angina, > New York Heart Association (NYHA) class III congestive heart failure or myocardial infarction (MI) within 6 months prior to study enrollment
  • Diagnosed congenital long QT syndrome
  • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
  • Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
  • Subjects who are detained or imprisoned are not eligible
  • History of significant bleeding disorder unrelated to cancer, including:

    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
    • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • May not take concomitant medications that are generally accepted to have a risk of causing Torsades de Pointes including: (patients must discontinue drug 7 days prior to starting dasatinib)

    • Quinidine, procainamide, disopyramide
    • Amiodarone, sotalol, ibutilide, dofetilide
    • Erythromycin, clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, sparfloxacin, lidoflazine
  • Patients already taking other CYP inducers or inhibitors other than those listed above are eligible for the study only after principal investigator (PI) review; dose adjustments and/or monitoring of drug levels where applicable will be made as needed by the PI after consultation with pharmacy
  • Women who:

    • Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or
    • Have a positive pregnancy test at baseline, or
    • Are pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01441882

United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Stephen Spurgeon OHSU Knight Cancer Institute

Responsible Party: Stephen Spurgeon, Associate Professor, OHSU Knight Cancer Institute Identifier: NCT01441882     History of Changes
Other Study ID Numbers: IRB00006146
NCI-2011-03136 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HEM 10010-L
BMS CA180-280
IRB00006146 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( U.S. NIH Grant/Contract )
First Posted: September 28, 2011    Key Record Dates
Results First Posted: February 15, 2018
Last Update Posted: February 15, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action