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  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  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 < %), 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 highly effective methods of contraception during dosing and for  days after the last dose of PDR; 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  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 < %), 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  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  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  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 < %), 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  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  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  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\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  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 two 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  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  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 < %), 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  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  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 MCS, 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  months after the last dose of MCS. 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  months after completion of MCS 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  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 < %), 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  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 throughout the study and for at least  months after\r\ncompletion of treatment; 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* Male sterilization (at least  months prior to screening); the vasectomized male partner should be the sole partner for that patient\r\n* Use of  highly effective method of contraception, and  additional (barrier) method, at the same time\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  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  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  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 =< %), 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  months before taking study treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  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               . mUFC > . x ULN (Mean of three -hour urine samples collected preferably on \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 ),\n                  with ? of the individual UFC values being > . x ULN.\n\n               . Morning plasma ACTH above Lower Limit of Normal\n\n               . 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 >  mm OR iii.\n             Bilateral inferior petrosal sinus sampling (BIPSS) with either CRH or DDAVP\n             stimulation for patients with a tumor ? mm. The criteria for a confirmatory BIPSS\n             test are any of the following: Pre-dose central to peripheral ACTH gradient > ;\n             Post-dose central to peripheral ACTH gradient >  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  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 >  ms for males and QTcF >  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 .\n\n          -  Patients likely to require adrenalectomy, pituitary surgery, or radiation therapy\n             during the placebo-controlled period (Weeks -) 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  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-, 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. . 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  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  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          . Use of oral*, injected, or implanted hormonal methods of contraception or other forms\n             of hormonal contraception that have comparable efficacy (failure rate <%), for\n             example hormone vaginal ring or transdermal hormone contraception\n\n          . Placement of an intrauterine device (IUD) or intrauterine system (IUS)\n\n          . 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 \n             months before taking study drug. Women are considered post-menopausal and not of child\n             bearing potential if they have had  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.
Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:\r\n* Sexually active males should use a condom during intercourse while taking drug and for  weeks after the final dose of study treatment and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least  weeks after the final dose of study 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, 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 sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female study subjects, the vasectomized male partner should be the sole partner for that patient)\r\n* Use a 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: hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed\r\n** Women are considered post-menopausal and not of child-bearing potential if they have had  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) at least six weeks ago\r\n** For women with therapy-induced amenorrhea, oophorectomy or serial measurements of follicle stimulating hormone (FSH) and/or estradiol are needed to ensure postmenopausal status\r\n** NOTE: ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
Women of childbearing potential (WOCBP) or partners of WOCBP participating in this study must agree to use highly effective contraception while on treatment and for at least  weeks after end of treatment; 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\r\n* Highly effective contraception methods include combination of:\r\n** Any two of the following:\r\n*** Use of oral, injected or implanted hormonal methods of contraception or\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** Total abstinence or\r\n** Male/female sterilization\r\n* Women are considered post-menopausal and not of child-bearing potential if they have had  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 enrollment; 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
Patients who are pregnant or breast-feeding are not eligible for this study; fertile patients may not participate unless they have agreed to use contraception during and for  months after T cell infusion; 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* Sterilization: Patient has 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 study patients, the vasectomized male partner should be the sole partner for that patient]\r\n* Use a combination of the following:\r\n** Hormonal contraception (oral or injected) or placement of an intrauterine device (IUD) or an intrauterine system (IUS)\r\n** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with\r\nspermicidal foam/gel/film/cream/vaginal suppository\r\nNote: Women are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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; male patients must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom); a condom is required to be used also by vasectomized men in order to prevent delivery of the study treatment via seminal fluid
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  month days after stopping study drug; highly effective contraception methods include: \r\n* Total abstinence or \r\n* Male or female sterilization or \r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted 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* Women are considered post-menopausal and not of child bearing potential if they have had  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 must agree to use an adequate method of contraception during the study and until  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  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  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 < %), 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  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  months following infusion of ETL-ARTEMIS T cells and ETL-ARTEMIS T cells are no longer present by PCR (with surveillance to cease at  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: ) 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, ) tubal ligation at least six weeks before taking study treatment\r\n** Male sterilization at least  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 < %) for example hormonal vaginal ring or transdermal hormonal contraception; women on oral contraception should be stable on the hormone pill for at least  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  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)
Subjects who are pregnant or breast-feeding are not eligible for this study; fertile subjects may not participate unless they have agreed to use contraception during and for  months after T cell infusion\r\n* 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** Sterilization: Patient has 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 study subjects, the vasectomized male partner should be the sole partner for that patient]\r\n** Use a combination of the following:\r\n*** Hormonal contraception (oral or injected) or placement of an intrauterine device (IUD) or an intrauterine system (IUS)\r\n*** Barrier method of contraception: Condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Note: Woman are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom); a condom is required to be used also by vasectomized men in order to prevent delivery of the study treatment via seminal fluid
Women of child-bearing potential and men must agree to use highly effective contraception during the study and for  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  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 < %), 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  days before taking study treatment\r\n* Women are considered post-menopausal and not of childbearing potential if they have had  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  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:  year of natural (spontaneous) amenorrhea or surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least  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  weeks before taking study treatment; oophorectomy alone\r\nrequires follow up hormone level assessment for fertility\r\n* Male sterilization (at least  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 < %); (the dose of the contraceptive should be stable for  months)
Subjects who are pregnant or breast-feeding are not eligible for this study; fertile subjects may not participate unless they have agreed to use contraception during and for  months after T cell infusion; 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* Sterilization: patient has 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 study subjects, the vasectomized male partner should be the sole partner for that patient)\r\n* Use a combination of the following (both a+b):\r\n** Hormonal contraception (oral or injected) or placement of an intrauterine device (IUD) or an intrauterine system (IUS)\r\n** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Note: woman are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom); a condom is required to be used also by vasectomized men in order to prevent delivery of the study treatment via seminal fluid
Women of child-bearing potential (WCBP), defined as all women capable of becoming pregnant, won't use highly effective methods of contraception during the study and  weeks after. Highly effective contraception methods include combination of any two 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* Total abstinence or\r\n* Male/female sterilization\r\n* Women are considered post-menopausal and not of child-bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile, or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to study entry. 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 childbearing potential
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  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  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 < %), 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 (WOCBP), defined as all women physiologically capable of becoming pregnant, must agree to use highly effective contraception during study treatment and for  days after study discontinuation; highly effective contraception is defined as either:\r\n* True 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: Surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; 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 must be the sole partner for that participant\r\n* Use of a combination of any two 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** Appropriate hormonal contraceptives (including any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent  including oral, subcutaneous, intrauterine, or intramuscular agents)
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  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  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 < %), 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  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  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  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 < %), 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
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for  months following the last dose of deferasirox\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment; effective contraception methods include:\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** Total abstinence or (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  months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject \r\n* Women are considered post-menopausal and not of child bearing potential if they have had  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; sexually active males must use a condom during intercourse while taking drug and for  days after stopping study medication and 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 must agree to use an adequate method of contraception during the study and until  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  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  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 < %), 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  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  days prior to the first dose of study treatment, and must agree to use highly effective methods of contraception during dosing and for  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 < %), 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  months before taking study treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  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  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  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 < %), 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 BGJ 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  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
Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:\r\n* Sexually active males should use a condom during intercourse while taking drug and for  weeks after the final dose of study treatment and 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\r\n* 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  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  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):\r\n*** a. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** b. 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, defined as all women physiologically capable of becoming pregnant, must agree to use highly effective methods of contraception during dosing and for  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  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 < %); 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  days after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence\r\n* Female sterilization-bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least  weeks before starting study treatment; 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\r\n* Male sterilization of subject partner- vasectomy at least  months prior to screening\r\n* Combination of any two of the following:\r\n** Use of oral, injected, or implanted 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* Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or  months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >  mIU/mL (for United States [US] only: and estradiol <  pg/mL)
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  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 < %), 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  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  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, must use highly effective methods of contraception during the study and  weeks after; highly effective contraception methods include combination of any two of the following: 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, total abstinence or male/female sterilization; women are considered post-menopausal and not of child-bearing potential if they have had  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 treatment; 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  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 < %), 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  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  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  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  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  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 < %), 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  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  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  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 < %), 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  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  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  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 < %), 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  months before taking study treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  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  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  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  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  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  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 < %), 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  months before taking study treatment; women are considered post-menopausal and not of child bearing potential if they have had  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
Patient is NOT pregnant or breast-feeding; fertile patient MUST agree to use contraception during and for  months after T cell infusion\r\n* 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** Sterilization: patient has 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 study patients, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a combination of the following (both):\r\n*** Hormonal contraception (oral or injected) or placement of an intrauterine device (IUD) or an intrauterine system (IUS)\r\n*** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Note: women are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom); a condom is required to be used also by vasectomized men in order to prevent delivery of the study treatment via seminal fluid
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  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  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 < %), 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  months before taking study treatment\r\nWomen are considered post-menopausal and not of child bearing potential if they have had  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, must use highly effective contraception during treatment and for  additional weeks after stopping treatment; the highly effective contraception is defined as either:\r\n* True 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 ago; 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 patient\r\n* Use of a combination of any two of the following (a+b):\r\na) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\nb) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository \r\n* Oral contraception, injected or implanted hormonal methods are not allowed \r\n* Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment and for an additional  weeks after stopping treatment\r\n* Female partner of male study subject should use highly effective contraception during dosing of any study agent and for  weeks after final dose of study therapy
Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through  months after the final dose of study 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 patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n** Sterilization: patient has 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 study patients, the vasectomized male partner should be the sole partner for that patient); OR\r\n** Use a combination of the following (both a+b): \r\n*** Placement of a non-hormonal intrauterine device (IUD) or non-hormonal intrauterine system (IUS)\r\n*** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n** Note: hormonal contraception methods (e.g. oral, injected, implanted) are not allowed \r\n** Note: women are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for  months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid
Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives are not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least  consecutive months (i.e., who has had menses any time in the preceding  consecutive months), must have a negative serum pregnancy test =<  hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL (for United States [US] only: and estradiol <  pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment and for  weeks after stopping treatment\r\n* The highly effective contraception is defined as either:\r\n** True 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 ago; 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 patient\r\n** Use of a combination of any two of the following (a+b):\r\na) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\nb) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n** Oral contraception, injected or implanted hormonal methods are not allowed \r\n** Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment, for  weeks after stopping treatment and for additional  weeks ( weeks in total after study drug discontinuation) and should not father a child in this period\r\n** Female partner of male study subject should use highly effective contraception during dosing of any study agent and for  weeks after final dose of study therapy
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  days after study treatment; highly effective contraception methods include: total abstinence or male partner or female sterilization or combination of any two of the following (a+b or a+c, or b+c): a) use of oral, injected or implanted hormonal methods of contraception, b) placement of an intrauterine device (IUD) or intrauterine system (IUS), c) barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Note: postmenopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they have had  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, a woman is considered to be of not child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment
Any of the following:\r\n* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (>  mIU/mL)\r\n* Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through  months after the final dose of study 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 patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n** Sterilization: patient has 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 study patients, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a combination of the following (both a+b):\r\n*** Placement of a non-hormonal intrauterine device (IUD) or non-hormonal intrauterine system (IUS)\r\n*** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n** Note: hormonal contraception methods (e.g. oral, injected, implanted) are not allowed \r\n** Note: woman are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for  months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid\r\n* Sexually active males who are unwilling to use a condom during intercourse while taking drug and for  months after stopping investigational medications and agree not to father a child in this period
Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least  consecutive months (i.e., who has had menses any time in the preceding  consecutive months), must have a negative serum pregnancy test =<  hours prior to initiating treatment; women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL (for United States [US] only: and estradiol <  pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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, must use highly effective contraception during the study and for  half-lives (T/) ( days) after stopping treatment; the highly effective contraception is defined as either:\r\n* True 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* Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; 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 vasectomised male partner should be the sole partner for that patient\r\n* Use of a combination of any two of the following (a+b):\r\na) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\nb) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Oral contraception, injected or implanted hormonal methods are not allowed as BKM potentially decreases the effectiveness of hormonal contraceptives\r\n* Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment, for  T/ ( days) after stopping treatment and for additional  weeks ( months in total after study drug discontinuation) and should not father a child in this period
Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:\r\n* Sexually active males should use a condom during intercourse while taking BYL and for  weeks after the final dose of BYL, and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid; moreover, sexually active males should not father a child for  months after completion of radiation per standard clinical practice\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least  weeks after the final dose of BYL; moreover, per standard clinical practice, women should not become pregnant for  months after completion of radiation; 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, 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 sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); [for female study subjects, the vasectomized male partner should be the sole partner for that patient]\r\n** Use a combination of the following (both a+b):\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: Hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed as alpelisib may decrease the effectiveness of hormonal contraceptives\r\n* NOTE: Women are considered post-menopausal and not of child-bearing potential if they have had  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) at least six weeks ago
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  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  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 < %), 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  months before taking study treatment
Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; breastfeeding should be discontinued if the mother is treated with BKM and olaparib or BYL and olaparib; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least  consecutive months (i.e., who has had menses any time in the preceding  consecutive months), must have a negative serum pregnancy test =<  hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >  mIU/mL (for United States [US] only: and estradiol <  pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for  T/ ( days) after stopping treatment and for additional  weeks ( months in total after study drug discontinuation); the highly effective contraception is defined as either:\r\n** True 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 ago; 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 patient\r\n** Use of a combination of any two 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* Oral contraception, injected or implanted hormonal methods are not allowed\r\n* Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment, for  T/ ( days) after stopping treatment and for additional  weeks ( months in total after study drug discontinuation) and should not father a child in this period
Patient who is not willing to apply highly effective contraception during the study and through the duration as defined below:\r\n* Sexually active males should use a condom during intercourse while taking drug and for  weeks after the final dose of study treatment and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least  weeks after the final dose of study treatment\r\n* 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, 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 sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female study subjects, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a combination of the following (both a+b):\r\n*** a. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** b. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n*** c. Note: hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed as buparlisib decreases the effectiveness of hormonal contraceptives
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  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  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  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  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  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  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 < %), 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  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
Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:\r\n* Sexually active males should use a condom during intercourse while taking drug and for  weeks after the final dose of study treatment and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least  weeks after the final dose of study 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, 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 sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female study subjects, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a combination of the following (both a+b):\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: hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed\r\n* Women are considered post-menopausal and not of child-bearing potential if they have had  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) at least six weeks ago\r\n* For women with therapy-induced amenorrhea, oophorectomy or serial measurements of follicle stimulating hormone (FSH) and/or estradiol are needed to ensure postmenopausal status\r\n* NOTE: ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
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  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  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 < %), 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  months before taking study treatment\r\n* Sexually active males unless they use a condom during intercourse while taking drug and for  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
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  weeks after the final 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 partner sterilization (at least  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 methods:\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: Post-menopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they are:\r\n** Aged >= ;\r\n** Or aged <  and have had  months of natural (spontaneous, in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) amenorrhea with and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range (serum FSH >  mIU/mL and estradiol <  pg/mL or according to the postmenopausal range definition for the local laboratory involved)\r\n** Or have had surgical bilateral oophorectomy (with or without hysterectomy)\r\n* For women with therapy-induced amenorrhea, oophorectomy or serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status; NOTE: ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and  weeks after stopping treatment; highly effective contraception methods include total abstinence, male partner sterilization (with post-vasectomy documentation of the absence of sperm in the ejaculate), or a combination of any two of the following:\r\n* Use of oral, injected or implanted hormonal methods of contraception o In case of use of oral contraception, women should have been stable on the oral agent before taking study treatment\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\nWomen are considered to be physiologically capable of becoming pregnant unless:\r\n* They have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms);\r\n* They have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization\r\n** 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, must use highly effective methods of contraception during the study and  weeks after ending treatment; highly effective contraception methods include combination of any two of the following:\r\n* Use of oral, injected or implanted hormonal methods of contraception or\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* Total abstinence\r\n* Male/female sterilization\r\nWomen are considered post-menopausal and not of child-bearing potential if they have had  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 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 (WOCBP), defined as women physiologically capable of becoming pregnant, must use one additional highly effective methods of contraception in addition to the LIUD during the study and  weeks after; acceptable effective contraception methods include combo of the following: a) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; b) total abstinence or; c) male/female sterilization; women are considered post-menopausal and not of child-bearing potential if they have had  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 > six weeks prior to randomization
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  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 < %), 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  months before taking study treatment\r\n** Women are considered post-menopausal and not of child bearing potential if they have had  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  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  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  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 < %), 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  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, must use highly effective contraception during study treatment and for  days after study discontinuation; highly effective contraception is defined as either:\r\n* True 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* Sterilization: surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment (as described above)\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 participant\r\n* Use of a combination of any two 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** Appropriate hormonal contraceptives (including any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent - including oral, subcutaneous, intrauterine, or intramuscular agents)
Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment: \r\n* Sexually active males should use a condom during intercourse while taking drug and for  weeks after the final dose of study treatment and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least  weeks after the final dose of study 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, 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 sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female study subjects, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a 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: hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed\r\n* Women are considered post-menopausal and not of child-bearing potential if they have had  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) at least six weeks ago
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation; women of child-bearing potential must have a negative serum pregnancy test during screening; 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 and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and  months after completion of AEB and BYL administration; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during dosing\r\n* Highly effective contraception methods include:\r\n** Total abstinence OR\r\n** Male or female sterilization OR\r\n** Combination 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* Women are considered post-menopausal and not of child bearing potential if they have had  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  weeks after; women are considered post-menopausal and not of child-bearing potential if they have had  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 % 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  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 who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives are not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least  consecutive months (i.e., who has had menses any time in the preceding  consecutive months), must have a negative serum pregnancy test =<  hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >  mIU/mL (for United States [US] only: and estradiol <  pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for  weeks ( T/) (after stopping treatment); the highly effective contraception is defined as either:\r\n** True 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 ago; 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 vasectomised male partner should be the sole partner for that patient\r\n** Use of a combination of any two of the following (a+b):\r\n*** a) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** b) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Oral contraception, injected or implanted hormonal methods are not allowed\r\n* Fertile males, defined as all males physiologically capable of conceiving offspring must use condoms during treatment, for  weeks ( T/) after stopping treatment and for an additional  weeks ( weeks in total after study drug discontinuation) and should not father a child in this period\r\n* Female partner of male study subject should use highly effective contraception during dosing of any study agent and for  weeks after final dose of study therapy
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and  months after; hormonal contraception methods (e.g. oral, injected, implanted) are not allowed; highly effective contraception methods include combination of any two of the following: a) placement of a non-hormonal intrauterine device (IUD) or non-hormonal intrauterine system (IUS); b) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; c) 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); or d) male/female sterilization; (sterilization: patient has 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 partner sterilization [with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate]; [for female study patients, the vasectomized male partner should be the sole partner for that patient]); women are considered post-menopausal and not of child-bearing potential if they have had  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 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
Any of the following:\r\n* Pregnant women\r\n* Nursing women\r\n* Men or women of childbearing potential who are unwilling to employ adequate contraception during the study and through  months after the final dose of study treatment if female, and for  months after final dose of study treatment if male\r\n* NOTE: adequate 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** Sterilization: patient has 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 study patients, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a combination of the following:\r\n*** Placement of a non-hormonal intrauterine device (IUD) or non-hormonal intrauterine system (IUS)\r\n*** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n**** Note: hormonal contraception methods (e.g. oral, injected, implanted) are not allowed as it cannot be ruled out that the study drug decreases the effectiveness of hormonal contraception \r\n**** Note: women are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n**** Note: male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for  months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid
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  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  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  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 BYL 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  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  months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject
Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for  weeks ( T/) (after stopping treatment); the highly effective contraception is defined as either:\r\n** True 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 ago; 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 patient\r\n** Use of a combination of any two of the following (a+b):\r\n*** a) Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** b) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Oral contraception, injected or implanted hormonal methods are not allowed \r\n* Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment, for  weeks ( T/) after stopping treatment and for additional  weeks ( weeks in total after study drug discontinuation) and should not father a child in this period\r\n* Female partner of male study subject should use highly effective contraception during dosing of any study agent and for  weeks after final dose of study therapy
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and  weeks after; highly effective contraception methods include combination of any two of the following:\r\n* Use of oral, injected or implanted hormonal methods of contraception, or\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* Total abstinence \r\n* Male/female sterilization\r\n* Women are considered post-menopausal and not of child-bearing potential if they have had  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 randomization; in the case of oophorectomy alone, only when reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential
Adults of reproductive potential must be able and agree to use appropriate contraception; double barrier contraceptives must be used throughout the trial by both sexes\r\n* Women of childbearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least  consecutive months (i.e., who have had menses any time in the preceding  consecutive months), must have a negative serum pregnancy test =<  hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >  mIU/mL (and estradiol <  pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study; women assigned to ARMS AC and D must use highly effective contraception for  weeks after stopping treatment; women assigned to ARM A must continue contraceptive measures for  weeks after stopping treatment; women assigned to ARM B must continue contraceptive measures for  weeks after stopping treatment; the highly effective contraception is defined as either:\r\n** True 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 ago; 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 patient\r\n** Use of a combination of any two 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 childbearing potential must agree to use an adequate method of contraception during the study and until  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  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  months prior to screening)
Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least  consecutive months (ie, who has had menses any time in the preceding  consecutive months), must have a negative serum pregnancy test =<  hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL (for US only: and estradiol <  pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through  months after the final dose of study treatment; for males with partners with childbearing potential, highly effective contraception is required for  months; the highly effective contraception is defined as either:\r\n** True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, 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 ago; 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 patient\r\n** Use of a combination of any two of the following (a+b):\r\n*** a. Placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n*** b. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n* Oral contraception, injected or implanted hormonal methods are not allowed\r\n* Fertile males, must use highly effective (double barrier) methods of contraception (eg, spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for  months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid; female partner of male study subject should use highly effective contraception during dosing of any study agent and for  weeks after final dose of study therapy\r\n* Note: hormonal contraception methods (eg, oral, injected, implanted) are not allowed\r\n* Note: woman are considered post-menopausal and not child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to  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  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  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 < %), 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  months before taking study treatment; women are considered post-menopausal and not of child bearing potential if they have had  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
Men of reproductive potential and their female partners must use highly effective contraception during treatment, for  half-lives ( days) after stopping treatment and for additional  weeks ( months in total after study drug discontinuation) and should not father a child in this period; the highly effective contraception is defined as either:\r\n* True 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: female partners have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; 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 participant sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)\r\n* Use of a combination of any two of the following (a+b):\r\n** a) Female partner with prior placement of an intrauterine device (IUD) or intrauterine system (IUS)\r\n** b) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n** Oral contraception use by female partners, injected or implanted hormonal methods are not allowed as BKM potentially decreases the effectiveness of hormonal contraceptives\r\n** Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment, for  T/ ( days) after stopping treatment and for additional  weeks ( months in total after study drug discontinuation) and should not father a child in this period
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  months after the last study treatment; highly effective contraception methods include the following:\r\n* Total abstinence\r\n* Male or female sterilization\r\n* Combination of any two of the following:\r\n** Use of oral, injected, or implanted hormonal methods of contraception\r\n** Placement of an intrauterine (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 child bearing potential if they have had  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 initiation of the study; 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  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  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  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): () use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <%), 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  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 unless they are using highly effective methods of contraception during dosing and for  days after study treatment:\r\n* Total abstinence or\r\n* Male or female sterilization or\r\n* Combination of any two of the following:\r\n** Use of oral, injected or implanted 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* Post-menopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they have had  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  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  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 < %), 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  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  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 < %), 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  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  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
Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:\r\n* Sexually active males should use a condom during intercourse while taking drug and for  weeks after the final dose of study treatment and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least  weeks after the final dose of study treatment\r\n* 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** 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 sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female study subjects, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a 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: hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed
Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment\r\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through  months after the final dose of study 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 patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n** Sterilization: patient has 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 study patients, the vasectomized male partner should be the sole partner for that patient)\r\n** Use a combination of the following (both of the following):\r\n*** Placement of a non-hormonal intrauterine device (IUD) or non-hormonal intrauterine system (IUS)\r\n*** Barrier method of contraception: condom or occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\r\n** Note: hormonal contraception methods (e.g. oral, injected, implanted) are not allowed to count as contraception; patients are able to continue taking oral contraceptives if desired\r\n** Note: women are considered post-menopausal and not of child bearing potential if they have had  months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels >  mIU/mL and estradiol <  pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) 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\r\n* Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and continue using contraception and refrain from fathering a child for  months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid\r\n* Sexually active males who are unwilling to use a condom during intercourse while taking the study drug and for  months after stopping investigational medications and agree not to father a child in this period\r\n* Patients unwilling or unable to comply with the protocol
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  weeks after study drug discontinuation; women are considered post-menopausal and not of child bearing potential if they have had  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 < %), 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  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          . Written informed consent must be obtained before any assessment was performed.\n\n          . Male and female patients at least  years of age.\n\n          . Patients weighed between  - kg to participate in the study, and had a body mass\n             index (BMI) within the range of  -  kg/m\n\n          . 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  hours of planned dosing day.\n\n          . 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  months or local\n             assays could be used to qualify the patient for enrollment.\n\n          . 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          . Use of other investigational drugs at the time of enrollment, or within  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          . History of hypersensitivity to any of the study drugs or to drugs of similar chemical\n             classes.\n\n          . Karnofsky performance score <%.\n\n          . Had HCMV-related organ disease within  months prior to enrollment.\n\n          . Detectable HCMV infection (positive pp antigenemia or plasma HCMV DNA polymerase\n             chain reaction (PCR) assays prior to enrollment from samples collected within  days\n             prior to enrollment. Local assays could be used to qualify the patient for enrollment.\n\n          . Received any of the following within  days prior to enrollment: ganciclovir,\n             valganciclovir, foscarnet, cidofovir, acyclovir (> mg/kg/day IV), valacyclovir (>\n             gm/day oral), famciclovir (> mg/day oral), HCMV immune globulin, immune globulin\n             (> mg/kg), or any other medication with anti-HCMV activity.\n\n          . Required mechanical ventilation within  days prior to enrollment.\n\n          . Received any vasopressors or other agents for hemodynamic support within  days prior\n             to enrollment. These agents included but are not limited to epinephrine, metaraminol,\n             norepinephrine, dopamine, vasopressin, phenylephrine, and dobutamine.\n\n          . Impaired renal function requiring dialysis.\n\n         . 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 > mg/dL). The investigator\n             should make this determination in consideration of the subject's medical history and\n             laboratory data.\n\n         . Severe liver disease or liver injury as indicated one or more of the following:\n\n               -  Alanine aminotransferase (ALT) >-times the upper limit of normal (ULN).\n\n               -  Aspartate aminotransferase (AST) >-times the upper limit of normal.\n\n               -  Gamma-glutamyl transferase (?-GT) >-times the upper limit of normal.\n\n               -  Serum total bilirubin (TBL) >-times the upper limit of normal.\n\n         . 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         . 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  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                  %), 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  months before taking study treatment. Women were considered\n                  post-menopausal and not of child bearing potential if they had  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         . 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.