Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effective contraception methods include:\r\n* Total abstinence when this is in line with the preferred and usual lifestyle of the patient\r\n* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n* Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient\r\n* Combination of the 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 at least 3 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 6 months prior to screening); the vasectomized male partner should be the sole partner for that patient\r\n* Use of 1 highly effective method of contraception, and 1 additional (barrier) method, at the same time\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
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 16 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 16 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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 8 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to 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 12 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 12 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 > 40 mIU/mL and estradiol < 20 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 3 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
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 12 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 12 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 > 40 mIU/mL and estradiol < 20 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
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 12 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 12 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 > 40 mIU/mL and estradiol < 20 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 12 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 12 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 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 120 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)
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 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 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject \r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential; sexually active males must use a condom during intercourse while taking drug and for 28 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
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 8 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 3 months following the discontinuation of study treatment; highly effective contraception methods include:\r\n** Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods]) and withdrawal are not acceptable methods of contraception\r\n** Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\r\n** Male sterilization (at least 6 months prior to screening); for female 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 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 15 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 6 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 6 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 pg/mL)
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 8 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to 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
Patient is NOT pregnant or breast-feeding; fertile patient MUST agree to use contraception during and for 12 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 12 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 > 40 mIU/mL and estradiol < 20 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, must use highly effective contraception during treatment and for 16 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 16 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 16 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 6 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 12 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 > 40 mIU/mL and estradiol < 20 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 6 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 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 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 4 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 4 weeks after stopping treatment and for additional 12 weeks (16 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 16 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 90 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, 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 (> 5 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 6 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 12 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 > 40 mIU/mL and estradiol < 20 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 6 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 6 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 P450 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 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 48 hours prior to initiating treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 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 5 half-lives (T1/2) (8 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 BKM120 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 5 T1/2 (8 days) after stopping treatment and for additional 12 weeks (3 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 BYL719 and for 16 weeks after the final dose of BYL719, 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 6 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 12 weeks after the final dose of BYL719; moreover, per standard clinical practice, women should not become pregnant for 12 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago
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 BKM120 and olaparib or BYL719 and olaparib; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 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 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 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 5 T1/2 (8 days) after stopping treatment and for additional 12 weeks (3 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 5 T1/2 (8 days) after stopping treatment and for additional 12 weeks (3 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 16 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 4 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
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 16 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 12 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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 8 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 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject\r\n* Combination of the following 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 >= 60;\r\n** Or aged < 60 and have had 12 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 > 40 mIU/mL and estradiol < 10 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 8 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 12 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 8 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to 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 8 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation > six weeks prior to randomization
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 120 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 16 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 16 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) 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 4 months after completion of AEB071 and BYL719 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Women 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 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 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 4 weeks (5 T1/2) (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 4 weeks (5 T1/2) after stopping treatment and for an additional 12 weeks (16 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 16 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 6 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to 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 20 months after the final dose of study treatment if female, and for 6 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 12 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 > 40 mIU/mL and estradiol < 20 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 6 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 are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL and estradiol < 20 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 4 weeks (5 T1/2) (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 4 weeks (5 T1/2) after stopping treatment and for additional 12 weeks (16 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 16 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 8 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to 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 12 consecutive months (i.e., who have had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL (and estradiol < 20 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 16 weeks after stopping treatment; women assigned to ARM A must continue contraceptive measures for 4 weeks after stopping treatment; women assigned to ARM B must continue contraceptive measures for 5 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 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 P450 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 12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment\r\n* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for US only: and estradiol < 20 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 20 months after the final dose of study treatment; for males with partners with childbearing potential, highly effective contraception is required for 6 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 6 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 16 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 12 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 > 40 mIU/mL and estradiol < 20 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
Men of reproductive potential and their female partners must use highly effective contraception during treatment, for 5 half-lives (8 days) after stopping treatment and for additional 12 weeks (3 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 BKM120 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 5 T1/2 (8 days) after stopping treatment and for additional 12 weeks (3 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 4 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to 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 child-bearing potential unless they are using highly effective methods of contraception during dosing and for 30 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 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
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 8 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 4 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 6 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 12 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 > 40 mIU/mL and estradiol < 20 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 6 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 6 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