Clinical trial NCT01206088: Tasigna in Glivec-resistant or Intolerant Patients in CML
Official title: A Phase IV Study for Nilotinib in Patients With Imatinib-resistant or Intolerant Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) in Chronic or Accelerated Phase.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: CML
Nilotinib
Imatinib Resistant
Imatinib Intolerant
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-09-21
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy and safety of nilotinib in patients with Imatinib resistant or intolerant CML-CP or AC. Efficacy evaluation will be made by Complete cytogenetic response rate(CCyR) at 12 months after nilotinib administration.


Eligibility criteria: Inclusion Criteria:

* Imatinib resistant chronic myelogenous leukemia in chronic phase with cytogenetic confirmation of Philadelphia chromosome.
* Documented chronic phase CML as defined by:

  * \< 15% blasts in peripheral blood and bone marrow
  * \< 30% blasts plus promyelocytes in peripheral blood and bone marrow
  * \< 20% basophils in the peripheral blood
  * ≥ 100 x 109/L (≥ 100,000 /mm3) platelets
  * No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
  * the patients with no CHR(complete hematologic response) after 3 months treatment, no mimical cytogenetic response(Ph+\<65%) after 6 months treatment, no major cytogenetic response(Ph+\<35%) after 12 months treatment.

Or

* Imatinib resistant Philadelphia positive CML-AC will be defined as at lease one following and no bast crisis before treatment.

  * \<30% and ≥ 15% blasts in peripheral blood and bone marrow
  * ≥ 30% blasts plus promyelocytes in peripheral blood and bone marrow
  * ≥ 20% basophils in the peripheral blood
  * \< 100 x 109/L (≥ 100,000 /mm3) platelets without related treatment
  * progression of CML-AP with Imatinib treatment, no hematologic response in bone marrow after at least 4 weeks treatment with imatinib. Progression from AP will be defined by increased numbers more than 50% of peripheral WBCs, blasts, basophils and platelets.
* definition of Imatinib intolerance in CML-CP and AP

  * the patients who discontinued imatinib treatment with any dosage due to Grade 3 or 4 non-hematologic adverse event or Grade 4 hematologic adverse event sustained for more than 7 days even best complementary therapy.
* WHO performance scale ≤ 2
* provide signed informed consent form

Exclusion Criteria:

* Cardiac dysfunction : LVEF \<45% by echocardiography, using pacemaker,Congenital long QT syndrome or a known family history of long QT syndrome, History of or presence of clinically significant ventricular or atrial tachyarrhythmias, Clinically significant resting brachycardia (\<50 beats per minute),QTc \> 450 msec on baseline ECG (using the QTcF formula), Myocardial infarction within 12 months prior to starting study, Other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension).
* Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
* Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
* History of significant congenital or acquired bleeding disorder unrelated to cancer.
* Treatment with any CSGF within 1 week of Day 1 except Erythropoietin.
* History of non-compliance to medical regimens or inability to grant consent.
* Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
* Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
* Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm.. Novartis must be contacted if a patient needs to be started on any of these drugs during study treatment.
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
* History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
* patients who diagnosed HIV infection.
* patients who has hypersensitivity for nilotinib or its additives
* Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug (Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval)
* Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial
* Patients with rare genetic disease such as galactose intolerance, moderate lactase deficiency or glucose-galactose absorption disorder

Primary outcomes:
measure: Complete cytogenetic response (CCyR) rate
timeFrame: at 12 months
Secondary outcomes:
measure: evaluation of safety by NCI-CTCAE version 3.0
timeFrame: until 12 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: St. Mary hospital, Catholic medical center
Study officials:
References: