A clinical research study evaluating the possibility to suspend the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients who have been for two different durations on Tasigna with a predifined level of molecular response.
- Conditions
- Adult patients with Ph+ chronic phase CML that have been treated with Imatinib for at least 2 years, are in CCyR, but have not achieved MR4.0 at study entry.MedDRA version: 19.0Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-005124-15-HU
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 565
• Male or female patients, aged = 18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0- 2;
• Documented confirmed diagnosis of chronic phase Ph+ and/or BCR-ABL+ CML. Documented chronic phase CML must meet all of the following criteria:
- < 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 hepato- and/or splenomegaly
• Previous first-line treatment with imatinib for a minimum of 24 months (even not continuously) in total and in imatinib treatment at time of enrollment;
• Patient in CCyR (a patient with MMR is considered to be in CCyR. Therefore, cytogenetic response (CgR) assessment has to be done if a patient has less than MMR in the local laboratory result and/or in the blood sample that was sent to the EUTOS standardized laboratory at the screening visit (patient will be considered screening failure if not in CCyR);
• Adequate end-organ function
• Patients must have the following electrolyte values within normal limits at screening analysis, or corrected to within normal limits with supplements prior to the first dose of study medication:
- Potassium
- Magnesium
- Total calcium
• Patients must have normal marrow function as defined below:
- Absolute Neutrophil Count (ANC) = 1.5 x 109/L.
- Hemoglobin =9.0 g/dL
- Platelets =100 x 109/L
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Written informed consent must be obtained prior to any screening procedures
For those patients consenting to participate in the optional Stem cells ENESTPath substudy or in the ‘CML patient’s voice’ Italian substudy, the same inclusion criteria for the ENESTPath study will be applicable, plus the following:
• Separate specific written informed consent for the Stem cells ENESTPath substudy or for the ‘CML patient’s voice’ Italian substudy must be obtained before starting any sub-study related assessment like but not limited to extraction of additional bone marrow samples for stem cells sub-study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 165
• Achievement of MR4.0 at study entry;
• Previous treatment with BCR-ABL inhibitors other than imatinib;
• Patients with detectable atypical BCR-ABL transcripts defined as absence of typical BCR-ABL transcripts for CML of the types b2(e13)-a2 or b3(e14)-a2 or both simultaneously documented at CML diagnosis or at any time before the screening procedure;
• Previous anticancer agents for CML except for imatinib, and/or cytoreduction after CML diagnosis, and/or interferon for less than 1 year;
• Known second chronic phase of CML after previous progression to AP/BC
• Known impaired cardiac function, including the following:
- Inability to determine the QT interval on ECG
- Complete left bundle branch block
- Right bundle branch block plus left anterior or posterior hemiblock
- Use of a ventricular paced pacemaker
- 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 bradycardia (<50 beats per minute)
- QTc >450 msec on the average of three serial baseline ECGs (using the QTcF formula). If QTcF >450msec and electrolytes are not within normal ranges, electrolytes should be corrected and the patient re-tested for the QTc
- History of clinically documented severe peripheral occlusive disease or severe ischemic cardiovascular disease (e.g. myocardial infarction, ischemic cerebral vascular disease) whenever in the opinion of the investigator other treatments could have a more favorable benefit/risk profile
- Other clinically significant heart disease (e.g., congestive heart failure or uncontrolled hypertension)
• Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol;
• History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis;
• Known presence of significant congenital or acquired bleeding disorder unrelated to cancer;
• History of other active malignancies within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, or previous cervical carcinoma in situ treated curatively;
• Patients who have not recovered from prior surgery;
• Treatment with other investigational agents within 4 weeks of Day 1;
• Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers or medications that have the potential to prolong the QT interval that cannot be either discontinued or switched to a different medication prior to starting study drug;
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
• Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) female of childbearing potential unwilling to use highly effective contraceptive precautions (as detailed below) throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential);
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 days after the final dose of nilotinib or imatinib. Patients using an oral hormonal contraception method should complete t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method