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 3 months of midostaurin medication; highly effective contraception methods include: \r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception \r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following (a+b or a+c, or b+c): \r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control while being treated on this study; “Women of child-bearing potential” is defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation. Highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Combination of any of the two following\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository\r\n* Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction; in case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods highly effective methods of contraception during dosing and for 150 days after the last dose of PDR001; Note: Highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment\r\n* For female participants, male sterilization (at least 6 months prior to screening); the vasectomized male partner should be the sole partner for that patient\r\n* Use of oral, injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening), the vasectomized male partner should be the sole partner for that patient \r\n* Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n* Note: In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment; Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction\r\n* Note: Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) is she considered not of child bearing potential
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effected contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient\r\n* Combination of any of the two following (a+b or a+c or b+c)\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception;\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS);\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository in case of use of oral contraception, women should have been stable on the same pill before taking study treatment\r\n* Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment; women of childbearing potential should be advised to use a highly effective method of contraception while receiving everolimus, and for up to 8 weeks after ending treatment; highly effective contraception is defined as either:\r\n* Total abstinence: when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)\r\n* Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female subjects on the study, the vasectomized male partner should be the sole partner for that subject)\r\n* Use of a combination of any two of the following:\r\n** Use of oral, injected, implanted or other hormonal methods of contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception women should have been stable on the oral agent before taking study treatment
The effects of MCS110, trametinib and dabrafenib on the developing human fetus are unknown. For this reason and because anti-cancer agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after the last dose of MCS110. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MCS110 administration. Highly Effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject\r\n* Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n* Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository)
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 30 days after stopping treatment; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate =< 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Key inclusion criteria:\n\n          -  Confirmed CD that is persistent or recurrent as evidenced by all of the following\n             criteria being met (i.e., a, b and c):\n\n               1. mUFC > 1.3 x ULN (Mean of three 24-hour urine samples collected preferably on 3\n                  consecutive days, during screening after washout of prior medical therapy for CD\n                  (if applicable), confirmed by the central laboratory and available before Day 1),\n                  with ?2 of the individual UFC values being > 1.3 x ULN.\n\n               2. Morning plasma ACTH above Lower Limit of Normal\n\n               3. Confirmation (based on medical history) of pituitary source of excess\n\n                  ACTH as defined by any one or more of the following three criteria:\n\n             i. Histopathologic confirmation of an ACTH-staining adenoma in patients who have had\n             prior pituitary surgery. OR ii. MRI confirmation of pituitary adenoma > 6 mm OR iii.\n             Bilateral inferior petrosal sinus sampling (BIPSS) with either CRH or DDAVP\n             stimulation for patients with a tumor ? 6mm. The criteria for a confirmatory BIPSS\n             test are any of the following: Pre-dose central to peripheral ACTH gradient > 2;\n             Post-dose central to peripheral ACTH gradient > 3 after either CRH or DDAVP\n             stimulation\n\n          -  Patients that received glucocorticoid replacement therapy must have discontinued such\n             therapy for at least seven days or 5 half-lives prior to screening, whichever is\n             longer.\n\n          -  Patients with de novo CD can be included only if they are not considered candidates\n             for surgery (e.g., poor surgical candidates due to co-morbidities, inoperable tumors,\n             patients who refuse to have surgical treatment, or surgical treatment is not\n             available).\n\n        Key exclusion criteria:\n\n          -  Patients with pseudo-Cushing's syndrome. This may be diagnosed by a normal late night\n             salivary cortisol value collected during the screening period and after washout of\n             prior CD medication.\n\n          -  Patients with risk factors for QTc prolongation or Torsade de Pointes, including:\n\n        patients with a baseline QTcF > 450 ms for males and QTcF > 460 ms for females; personal or\n        family history of long QT syndrome; concomitant medications known to prolong the QT\n        interval; patients with hypokalemia, hypocalcaemia, or hypomagnesaemia, if not corrected\n        before pre-dose Day 1.\n\n          -  Patients likely to require adrenalectomy, pituitary surgery, or radiation therapy\n             during the placebo-controlled period (Weeks 1-12) for the treatment of severe\n             hypercortisolism or pituitary tumor growth causing compression of the optic chiasm.\n\n          -  Patients with compression of the optic chiasm due to a macroadenoma or patients at\n             high risk of compression of the optic chiasm (tumor within 2 mm of optic chiasm).\n\n          -  Patients who have a known inherited syndrome as the cause for hormone over secretion\n             (i.e. Carney Complex, McCune-Albright syndrome, MEN-1, AIP).\n\n          -  Patients with Cushing's syndrome due to ectopic ACTH secretion or ACTH independent\n             (adrenal) Cushing's syndrome. Pregnant or nursing (lactating) women. 8. Women of\n             child-bearing potential, defined as all women physiologically capable of becoming\n             pregnant, unless they are using highly effective methods of contraception during\n             dosing and for 1 week after completion of dosing. Highly effective contraception\n             methods include: A. Total abstinence (when this is in line with the preferred and\n             usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation,\n             symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of\n             contraception. B. Female sterilization (have had surgical bilateral oophorectomy with\n             or without hysterectomy) or tubal ligation at least six weeks before taking study\n             drug. In case of bilateral oophorectomy, documentation is required (e.g. operative\n             report, pelvic ultrasound or other reliable imaging method). C. Male sterilization (at\n             least 6 months prior to screening). For female subjects on the study the vasectomized\n             male partner should be the sole partner for that subject.\n\n        D. Combination of any two of the following (a+b or a+c, or b+c):\n\n          1. Use of oral*, injected, or implanted hormonal methods of contraception or other forms\n             of hormonal contraception that have comparable efficacy (failure rate <1%), for\n             example hormone vaginal ring or transdermal hormone contraception\n\n          2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\n\n          3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault\n             caps) with spermicidal foam/gel/film/cream/vaginal suppository. *In the case of use of\n             oral contraception, women should have been stable on the same pill for a minimum of 3\n             months before taking study drug. Women are considered post-menopausal and not of child\n             bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with\n             an appropriate clinical profile (i.e., age appropriate, history of vasomotor symptoms)\n             or have had surgical bilateral oophorectomy (with or without hysterectomy), total\n             hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy\n             alone, only when the reproductive status of the woman has been confirmed by follow-up\n             hormone level assessment is she considered not of child bearing potential. Other\n             protocol-defined inclusion/exclusion criteria may apply.
Women of child-bearing potential, defined as all women capable of becoming pregnant, unless they are using two effective methods of contraception (unless patient is practicing total abstinence) during dosing and for 120 days after last dose, i.e., final vaccine; effective contraception methods include:\r\n* Female sterilization at least eight weeks before taking study treatment\r\n* Male sterilization (at least six months prior to screening)\r\n* Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%); in case of use of oral contraception, women should have been stable on the same pill for a minimum of 6 months before taking study treatment
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: \r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. \r\n* Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.\r\n* Combination of any of the two following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS). \r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository in case of use of oral contraception, women should have been stable on the same pill before taking study treatment.\r\n* Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, and all male participants must use effective methods of contraception for at least 12 months following infusion of ET190L1-ARTEMIS T cells and ET190L1-ARTEMIS T cells are no longer present by PCR (with surveillance to cease at 5 years)\r\n* Highly effective contraception may change depending on current Institutional Review Board (IRB) standards but currently include\r\n** Total abstinence, excluded are periodic abstinence utilizing the calendar, ovulation, symptothermal, or post-ovulation methods, or withdrawal technique\r\n** Female sterilization including: 1) surgical bilateral oophorectomy with or without hysterectomy; in the case of oophorectomy alone when the reproductive status has been confirmed by follow up hormone level assessment and, 2) tubal ligation at least six weeks before taking study treatment\r\n** Male sterilization at least 6 months prior to screening; in the case of female participants with a male partner who has had a vasectomy, this partner should be the sole partner for that patient\r\n** Contraception requiring consistent use of BOTH forms listed below must be utilized\r\n*** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%) for example hormonal vaginal ring or transdermal hormonal contraception; women on oral contraception should be stable on the hormone pill for at least 3 months prior to infusion of study drug\r\n*** Barrier method of contraception to include: condom, occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/vaginal suppository\r\n*** Sexually active males must use a condom during intercourse for 12 months after treatment as they should not father a child in this period; a condom is required to be used by vasectomized men (as well as during intercourse with a male partner)
Women of child-bearing potential and men must agree to use highly effective contraception during the study and for 3 months after stopping the study treatment; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male partner: male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following (a+b or a+c, or b+c):\r\n** A. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** B. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** C. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n** D. In case of use of oral contraception women should have been stable on the same pill for a minimum of 30 days before taking study treatment\r\n* Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up\r\nhormone level assessment is she considered not of childbearing potential\r\n* Sexually active males must agree to use a condom during intercourse while taking drug and for 3 months after stopping treatment; men should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Women of childbearing potential (post-menopausal or not of child-bearing potential) is defined by: 1 year of natural (spontaneous) amenorrhea or surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks ago; oophorectomy alone must confirmed by follow up hormone level assessment to be considered not of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception which includes:\r\n* Total abstinence (Periodic abstinence and withdrawal are not acceptable methods of contraception)\r\n* Female sterilization (bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment; oophorectomy alone\r\nrequires follow up hormone level assessment for fertility\r\n* Male sterilization (at least 6 months prior to screening); the vasectomized male partner should be the sole partner for that subject\r\n* Barrier methods of contraception: condom or occlusive cap\r\n* Use of oral, injected or implanted hormonal methods of contraception or other forms or hormonal contraception that have complete efficacy (failure < 1%); (the dose of the contraceptive should be stable for 3 months)
Women of child­bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post­-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study and for 30 days after the final dose of nilotinib; highly effective contraception is defined as either:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to enrolling); for female patients on the study the vasectomized male partner should be the sole partner for that patient\r\n* Use of a combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include: \r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception \r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment \r\n* Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient\r\n* Combination of any of the two following (a+b or a+c or b+c) \r\n** a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception \r\n** b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) \r\n** c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository In case of use of oral contraception, women should have been stable on the same pill before taking study treatment \r\n* Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any of the two following (a+b or a+c or b+c): a. use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception; b. placement of an intrauterine device (IUD) or intrauterine system (IUS); c. barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill before taking study treatment\r\n* Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Females of child bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum or urine beta human chorionic gonadotropin (b-hCG) pregnancy test results within 7 days prior to the first dose of study treatment, and must agree to use highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment; highly effective methods of contraception include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least six months prior to screening) with the appropriate post-vasectomy documentation of absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be sole partner for that subject\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or who have had a bilateral tubal ligation or hysterectomy
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 3 months following the discontinuation of study treatment must be used by both sexes (= female patients and their male partners); highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of the following (a+b or a+c, or b+c):\r\n** a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\nNote: Oral contraceptives (OC), injected or implanted hormonal methods are not allowed as the sole method of contraception because BGJ398 has not been characterized with respect to the potential to interfere with pharmacokinetics (PK) and/or the effectiveness of OCs\r\nPost-menopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must agree to use highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment; highly effective contraception methods include: \r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects the \tvasectomized male partner should be the sole partner\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%); for example, hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS) \r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; oral contraceptives (OC), injected or implanted hormonal methods are not allowed as the sole method of contraception
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 3 weeks after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n* In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n* * Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception \r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
CAPMATINIB EXCLUSION CRITERIA: Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 7 days after the last dose of capmatinib; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
CERITINIB EXCLUSION CRITERIA: Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 7 days after the last dose of capmatinib; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment
REGORAFENIB EXCLUSION CRITERIA: Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of entrectinib; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include: total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient; combination of any of the two following (a+b or a+c or b+c); use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill before taking study treatment; Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing 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 agree to continue for 3 months after the last dose of study treatment; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include: total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment; highly effective contraception methods include: \r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following: \r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing 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 agree to continue for 3 months after the last dose of study treatment; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\nIn case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\nWomen are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
TREATMENT: Women of childbearing potential and men must agree to use highly effective contraception (see list below) prior to study entry, for the duration of study participation, and for 3 months after completion of study\r\n* Total abstinence: when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)\r\n* Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female subjects on the study, the vasectomized male partner should be the sole partner for that subject)\r\n* Use of a combination of any two of the following (a+b or a+c or b+c):\r\n** Use of oral, injected, implanted or other hormonal methods of contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception, women should have been stable on the oral agent before taking study treatment\r\n* Sexually active males must use a condom during intercourse
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception from the day of transplant and for one week after infusion; high effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following (a+b or a+c, or b+c)\r\n** a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception women should have been stabile on the same pill for a minimum of 3 months before taking study treatment
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 12 weeks after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of tubal ligation alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening);for female patients on the study, the vasectomized male partner should be the sole partner for that patient\r\n* No patients with hormone receptor positive (HR+) disease should receive hormonal contraception, however the two following methods can be combined: placement of an intrauterine device (IUD) or intrauterine system (IUS) and barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient\r\n* Combination of any of the 2 following (a+b or a+c or b+c)\r\n** a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository\r\n*** In case of use of oral contraception, women should have been stable on the same pill before taking study treatment\r\n*** Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception \r\n*** Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing 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 3 months of midostaurin medication; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following (a+b or a+c, or b+c):\r\na) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\nb) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\nc) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n* Sexually active males unless they use a condom during intercourse while taking drug and for 5 months after stopping midostaurin medication; they should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; NOTE: periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); NOTE: for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following (a+b or a+c, or b+c):\r\n** a) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** b) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** c) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* NOTE:\r\n** In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment\r\n** Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) OR\r\n* Sexually active males unless they use a condom during intercourse while taking drug and for 5 months after stopping midostaurin medication\r\n* NOTE:\r\n** They should not father a child in this period\r\n** A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effective contraception methods include: total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient; combination of any of the two following (a+b or a+c or b+c) a. use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception b. placement of an intrauterine device (IUD) or intrauterine system (IUS) c. barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill before taking study treatment; note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women of childbearing potential (WOCBP) (including female pediatric patients who are menarcheal or who become menarcheal during the treatment), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after; women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms); highly effective methods of birth control have less than 1% chance of unwanted pregnancy during one year, if used appropriately according to the instruction of the manufacturer; highly effective contraception methods include combination of any two of the following:\r\n* Use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); or other forms of hormonal contraception that have comparable efficacy; in case of use of oral contraception women should have been stable on the oral agent for a minimum of 3 months before taking everolimus\r\n* Total abstinence or; male partner sterilization; (the vasectomized male partner should be the sole partner for that subject)\r\n* Female sterilization; have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to randomization; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not eligible for participation UNLESS they agree to use highly effective methods of contraception during dosing and for 5 weeks after study drugs discontinuation; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 5 weeks before receiving study treatment; in case of oophorectomy alone, the reproductive status of the woman must have been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of the following:\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n*** Note: Oral contraceptives (OC), injected or implanted hormonal methods are not allowed as the sole method of contraception, as BYL719 has not been characterized with respect to its potential to interfere with the PK and/or the effectiveness of OCs
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 3 months after midostaurin medication; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject
Females of child-bearing potential: willing to use two forms of effective contraception, and to continue use for 16 weeks (4 months) post last dose of study medication; effective contraception is defined as:\r\n* An intrauterine device with a documented failure rate of less than 1% per year\r\n* Male partner sterilization prior to the female subject’s entry, and this male is the sole sexual partner for that female\r\n* Complete abstinence from sexual intercourse for 14 days prior to enrollment, throughout study treatment, and for at least 4 months after the last dose of study treatment; abstinence is only acceptable when in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods, etc) and withdrawal are not acceptable methods of contraception\r\n* Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository)\r\nNote: hormonal-based methods (e.g., oral contraceptives) are not permitted as contraception; female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for 4 months following the last dose of study treatment; females of non-childbearing potential are those who are postmenopausal (defined as greater than 1 year without menses with an appropriate clinical profile, e.g., age appropriate, > 45 years in the absence of hormone-replacement therapy (HRT); in questionable cases, the subject must have a follicle-stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L); or who have had a bilateral tubal ligation or tubal occlusion, bilateral oophoredtomy or hysterectomy; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described from D1 of treatment, throughout the treatment period, and for 16 weeks after the last dose of study treatment; if a subject becomes pregnant during the treatment period of the study, the study treatments should be stopped immediately
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include: total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment male sterilization (at least 6 months prior to screening)
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy; WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product; highly effective contraception methods include:\r\n* (a) Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* (b) Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* (c) Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of any two of the following (a+b or a+c or b+c)\r\n* Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n* Placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include: (A) total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; (B) female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; (C) male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient (D) combination of any of the two following (a+b or a+c or b+c): (1) use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception (B) placement of an intrauterine device (IUD) or intrauterine system (IUS); (C) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository in case of use of oral contraception, women should have been stable on the same pill before taking study treatment; Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing 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 study treatment and for 3 months following the discontinuation of study treatment; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female patients on the study the vasectomized male partner should be the sole partner for that patient\r\n* Combination of the following (a+b or a+c, or b+c):\r\n** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS).\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; oral contraceptives (OC), injected or implanted hormonal methods are not allowed as the sole method of contraception
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient\r\n* Combination of any of the two following (a+b or a+c or b+c)\r\n** a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n** b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** c. Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* In case of use of oral contraception, women should have been stable on the same pill before taking study treatment\r\n* Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (defined below); highly effective contraception must be used by both sexes (female patients and their male partners) during study treatment and for 30 days after the last dose of study medication; highly effective contraception methods include:\r\n* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Combination of the following:\r\n** Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 12 weeks after study drug discontinuation; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception\r\n* In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment; Note: while oral contraceptives are allowed, they should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction
Inclusion Criteria:\n\n        Patients eligible for inclusion in this study had to fulfill all of the following criteria:\n\n          1. Written informed consent must be obtained before any assessment was performed.\n\n          2. Male and female patients at least 18 years of age.\n\n          3. Patients weighed between 45 -120 kg to participate in the study, and had a body mass\n             index (BMI) within the range of 18 - 34 kg/m2\n\n          4. Scheduled to undergo allogeneic bone marrow, peripheral blood stem cell, or cord blood\n             transplantation (transplant may be related or unrelated, T-cell depleted or non-T-cell\n             depleted, myeloablative or non-myeloablative/reduced intensity, haploidentical) and\n             began conditioning chemotherapy within 48 hours of planned dosing day.\n\n          5. Patient seropositive for HCMV before transplantation; donor could be seropositive or\n             seronegative for HCMV (donor positive/recipient or donor negative/recipient positive).\n             Historical patient HCMV serology data collected within the last 12 months or local\n             assays could be used to qualify the patient for enrollment.\n\n          6. Able to communicate well with the investigator, to understand and comply with the\n             requirements of the study.\n\n        Exclusion Criteria:\n\n        Patients fulfilling any of the following criteria were not eligible for inclusion in this\n        study:\n\n          1. Use of other investigational drugs at the time of enrollment, or within 5 half-lives\n             of enrollment, or until the expected PD (pharmacodynamic) effect has returned to\n             baseline, whichever is longer; or longer if required by local regulations.\n\n          2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical\n             classes.\n\n          3. Karnofsky performance score <50%.\n\n          4. Had HCMV-related organ disease within 6 months prior to enrollment.\n\n          5. Detectable HCMV infection (positive pp65 antigenemia or plasma HCMV DNA polymerase\n             chain reaction (PCR) assays prior to enrollment from samples collected within 14 days\n             prior to enrollment. Local assays could be used to qualify the patient for enrollment.\n\n          6. Received any of the following within 30 days prior to enrollment: ganciclovir,\n             valganciclovir, foscarnet, cidofovir, acyclovir (>25 mg/kg/day IV), valacyclovir (>3\n             gm/day oral), famciclovir (>1500 mg/day oral), HCMV immune globulin, immune globulin\n             (>500 mg/kg), or any other medication with anti-HCMV activity.\n\n          7. Required mechanical ventilation within 7 days prior to enrollment.\n\n          8. Received any vasopressors or other agents for hemodynamic support within 7 days prior\n             to enrollment. These agents included but are not limited to epinephrine, metaraminol,\n             norepinephrine, dopamine, vasopressin, phenylephrine, and dobutamine.\n\n          9. Impaired renal function requiring dialysis.\n\n         10. Any surgical or medical condition which might increase the risk for thrombotic events\n             if given immunoglobulins. These conditions included cryoglobulinemia, monoclonal\n             gammopathies, and hypertriglyceridemia (fasting level >1000 mg/dL). The investigator\n             should make this determination in consideration of the subject's medical history and\n             laboratory data.\n\n         11. Severe liver disease or liver injury as indicated one or more of the following:\n\n               -  Alanine aminotransferase (ALT) >5-times the upper limit of normal (ULN).\n\n               -  Aspartate aminotransferase (AST) >5-times the upper limit of normal.\n\n               -  Gamma-glutamyl transferase (?-GT) >5-times the upper limit of normal.\n\n               -  Serum total bilirubin (TBL) >3-times the upper limit of normal.\n\n         12. Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a\n             female after conception and until the termination of gestation, confirmed by a\n             positive human chorionic gonadotropin (hCG) laboratory test.\n\n         13. Women of child-bearing potential, defined as all women physiologically capable of\n             becoming pregnant, unless they were using effective methods of contraception during\n             dosing of study treatment.\n\n             Effective contraception methods included:\n\n               -  Total abstinence (when this is in line with the preferred and usual lifestyle of\n                  the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,\n                  post-ovulation methods) and withdrawal are not acceptable methods of\n                  contraception.\n\n               -  Female sterilization (have had surgical bilateral oophorectomy with or without\n                  hysterectomy) or tubal ligation at least six weeks before taking study treatment.\n                  In case of oophorectomy alone, only when the reproductive status of the woman was\n                  confirmed by follow up hormone level assessment.\n\n               -  Male sterilization (at least 6 months prior to screening). For female patients on\n                  the study, the vasectomized male partner should be the sole partner for that\n                  subject.\n\n               -  Barrier methods of contraception: Condom or Occlusive cap (diaphragm or\n                  cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository.\n\n               -  Use of oral, injected or implanted hormonal methods of contraception or other\n                  forms of hormonal contraception that have comparable efficacy (failure rate <\n                  1%), for example hormone vaginal ring or transdermal hormone contraception.\n\n               -  Placement of an intrauterine device (IUD) or intrauterine system (IUS). In case\n                  of use of oral contraception women would have been stable on the same pill for a\n                  minimum of 3 months before taking study treatment. Women were considered\n                  post-menopausal and not of child bearing potential if they had 12 months of\n                  natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age\n                  appropriate, history of vasomotor symptoms) or had surgical bilateral\n                  oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks\n                  ago. In the case of oophorectomy alone, only when the reproductive status of the\n                  woman had been confirmed by follow up hormone level assessment was she considered\n                  not of child bearing potential.\n\n         14. History of positive HIV (ELISA and Western blot) test result. Testing was not\n             required. No additional exclusions were applied by the investigator, in order to\n             ensure that the study population was representative of all eligible patients.