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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01441882
First received: September 21, 2011
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to estimate the biologic target activity of dasatinib in Chronic lymphocytic leukemia (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 cells, lymph node or spleen size).


Condition Intervention Phase
Chronic Lymphocytic Leukemia (CLL)
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • 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). [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    1. In vitro cytotoxicity = in vitro dasatinib sensitivity (IC50) of ≤50 nanomolar (nM) as determined in primary CLL cells via MTS assay.
    2. Clinical activity =as defined by a ≥50% decrease in absolute lymphocyte, count, and/or bone marrow CLL cells, lymph node or spleen size


Secondary Outcome Measures:
  • Drug safety and tolerability of dasatinib in patients with CLL by assessing the number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Overall Survival(OS) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: October 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib Drug: Dasatinib
Dasatinib will be administered at a starting dose of 140 mg by mouth once daily. Tablets come in 50 mg and 20 mg. Thus, 4 tablets will be taken once daily (20mg + 20mg + 50 mg + 50 mg) for a total of 140 mg daily. Dasatinib should be taken around the same time each day.
Other Name: Sprycel

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA)
  • Age >18 years old
  • Eastern Cooperative Oncology Group (ECOG) ≤2
  • In vitro dasatinib sensitivity (IC 50 ≤50 nm per MTS assay); samples obtained on electronic IRB (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 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 human chorionic gonadotropin (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.
  • 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, excluding low dose aspirin regimens

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
  • 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, lidoflazine.
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441882

Contacts
Contact: Jocelyn Adamo 503-418-2086 Digregor@ohsu.edu

Locations
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Stephen Spurgeon, M.D.    503-494-1551    Spurgeos@ohsu.edu   
Principal Investigator: Stephen Spurgeon         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Stephen Spurgeon, M.D. OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01441882     History of Changes
Other Study ID Numbers: OHSU-6146, NCI-2011-03136, HEM 10010-L
Study First Received: September 21, 2011
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
CLL
Dasatinib

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

ClinicalTrials.gov processed this record on September 30, 2014