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A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity

Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia (CLL)

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Trial Information

A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western World with
10,000 new cases per year in the United States and an estimated 4,500 deaths annually.
Currently, therapy seeks to calm symptoms and improve fevers. While many patients have
non-aggressive disease, requiring no or only irregular treatment, a large number of
patient's disease progresses rapidly, does not respond to treatment, and as a result,
patients die from their disease. A number of factors have been identified that help predict
poor outcomes including stage, genetic factors, and certain protein expression. However, the
investigators have little means available to determine which patients may benefit from
targeted treatment. Efforts have focused on blocking a certain protein family, which
recently showed promising results in CLL. Given dasatinib's (now referred to as the study
drug) ability to target those certain proteins, the investigators have examined the effects
of the study drug in primary CLL cells in a test tube and have gathered promising data
illustrating the effect of the study drug on cancer cells. Therefore, the investigators will
be conducting a clinical trial using the study drug in patients with relapsed/refractory or
poor risk CLL.

Inclusion Criteria:

- Written informed consent and Health Insurance Portability and Accountability

- Age >18 years old

- Eastern Cooperative Oncology Group(ECOG) ≤2

- In vitro dasatinib sensitivity (IC 50 ≤10 nm per MTS assay); samples obtained on eIRB
4422 may be used

- 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(1996 NCI working
group); Massive or progressive splenomegaly, Massive lymph nodes (≥10cm), 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

- Have adequate organ function: 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 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

- 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.

- After consent, discontinuation ("washout period") of any medications known to
contribute significantly to the risk of QT prolongation or interfere with Cytochrome
P(CYP3A4) mediated drug metabolism.

- Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy

- Patient agrees that IV bisphosphonates will be withheld for the first eight weeks of
dasatinib therapy

- Patient agrees to discontinue anti-coagulants and anti-platelet drugs.

Exclusion Criteria:

- Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy.

- Pleural or pericardial effusion of any grade

- Uncontrolled angina, >NYHA class III congestive heart failure or MI within 6 months
prior to study enrollment

- Diagnosed congenital long QT syndrome

- Any history of clinically significant ventricular arrhythmias

- 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

- 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,

- Patients already taking other CYP inducers or inhibitors other than those listed
above (and as noted in appendix F) are eligible for the study only after PI and
pharmacy review.

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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 lymph node size).

Outcome Description:

In vitro cytotoxicity = in vitro dasatinib sensitivity (IC50) of ≤10 nM as determined in primary CLL cells via MTS assay. Clinical activity = a decrease in absolute lymphocyte count (ALC) in the peripheral blood or bone marrow or measurable lymph nodes by 50%.

Outcome Time Frame:

Up to 24 weeks

Safety Issue:


Principal Investigator

Stephen Spurgeon, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

December 2014

Related Keywords:

  • Chronic Lymphocytic Leukemia (CLL)
  • CLL
  • Dasatinib
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



OHSU Knight Cancer Institute Portland, Oregon  97239