The purpose of this Cohort Treatment Plan is to allow access to Nilotinib for eligible patients diagnosed with imatinib-intolerant and/or resistant Philadelphia Chromosome positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Chronic Myelogenous Leukemia in Accelerated Phase (CML-AP), or Chronic Myelogenous Leukemia in Blast Crisis Phase (CML-BC). The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations.
The recommended dosing of nilotinib is 400 mg orally twice daily
Inclusion Criteria: - Age ≥ 18 years - One of the diagnoses listed below - Imatinib resistant Philadelphia chromosome positive CML in chronic phase and the presence of the following criteria: - < 15% blasts in peripheral blood or 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 liver or spleen - Imatinib resistant Philadelphia chromosome positive CML in accelerated phase defined as never in blast crisis before starting treatment with one or more of the following criteria present within 4 weeks prior to beginning treatment: - ≥ 15% but < 30% blasts in blood or bone marrow - ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc - Myocardial infarction within 12 months prior to starting nilotinib - Other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension). - Use of any medications that prolong the QT interval and CYP3A4 inhibitors if the treatment cannot be either safely discontinued or switched to a different medication prior to starting treatment. Please see http://crediblemeds.org/index.php for a comprehensive list of agents that prolong the QT interval - Severe and/ or uncontrolled concurrent medical disease that in the opinion of the treating physicians could cause unacceptable safety risks or compromise compliance with the compassionate use treatment (e.g. impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection, uncontrolled diabetes, ) - Patients who have undergone major surgery ≤ 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery - Known Cytopathologically confirmed Central Nervous System infiltration. - Use of therapeutic warfarin. - Acute or chronic liver or renal disease considered unrelated to tumor. - Treatment with any hematopoietic colony-stimulating growth factors ≤ 1 week prior to starting Nilotinib. Erythropoietin is allowed. - Patient who has not recovered from side effects of prior chemotherapy, immunotherapy, other investigational drugs, wide field radiotherapy, or major surgery. Patient who has received imatinib < 5 days prior to AMN107 or has not recovered from side effects of therapy. Hydroxyurea is permitted during the first 28 days of treatment (up to 5 g/day) for a maximum of 7 days. - Patient with a history of another primary malignancy that is currently clinically significant or requires active intervention. - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
Pregnancy statements and contraception requirements: - In accordance with good medical practice, clinical programs, Treatment Plans, in this case, should include measures that will minimize the possibility of fetal exposure to the investigational drug. Therefore, precautions should be taken in programs including women of childbearing potential. For these women, two criteria are given, one more and one less restrictive. Less restrictive wording is suggested for drugs in late development stage with complete negative repro toxicology data; in other cases, the more restrictive wording should be used. - For programs in which pre-menarche females could potentially be included, any female aged 8 years and above is to be treated as a woman of child-bearing potential, and this part of the definition should be added to the exclusion statement. - If there are potential drug-drug interactions between hormonal contraceptives and the treatment, the acceptable contraception method must be non-hormonal. - The patient Informed Consent for MAP participation must specify reproductive risks, compliance with adequate contraception methods, and permission to seek information regarding pregnancy outcome in case of an unintended pregnancy. In programs where abstinence is an allowable form of birth control, patients must agree to refrain from sexual activity. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method.
Adequate barrier methods of contraception include: diaphragm, condom (by the partner),
intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives
include any marketed contraceptive agent that includes an estrogen and/or a progestational