Current or prior diagnosis of AML
Participant must have metastatic CRPC or AML not amenable to curative therapy, refractory to standard of care therapy or for which standard of care therapy does not exist. Participants with AML who are candidates for stem cell transplantation must have been offered this therapeutic option. Must meet additional criteria specific for each diagnosis, metastatic CRPC and relapsing/remitting AML, as described in the protocol.
Received any previous treatment for AML
Subject has AML secondary to prior chemotherapy.
diagnosis of AML
Pathologically-confirmed diagnoses of relapsed AML: patients with AML that have relapsed at least once or are primary induction failure will be eligible
AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML) and except AML secondary to prior myelodysplastic syndrome. For Germany only: AML as defined by the WHO Classification either persisting/refractory after at least  primary induction courses (ie, no response after at least  prior chemotherapy cycles) or recurring after having achieved an initial response to chemotherapy except promyelocytic leukemia (APML) and except AML secondary to prior myelodysplastic syndrome.
AML (with the exception of AML M), patients with relapsed or refractory AML following treatment with cytotoxic chemotherapy or a targeted or biologic agent
AML (with the exception of AML M):
AML unsuitable for intensive chemotherapy
Subject must have received no prior treatment for AML; hydroxyurea is not considered a treatment and is allowed
> % bone marrow blasts at transplant if no history of AML and > % if had previous progression to AML;
Patients with AML or biphenotypic or bilineage leukemia (including a myeloid component) who have failed prior therapy; patients with AML should have failed prior therapy or have relapsed after prior therapy; patients with isolated extramedullary AML are eligible
Previously untreated AML (de novo or secondary) defined according to World Health Organization (WHO) criteria, excluding APL [AML with t(;)], with locally documented IDH and/or IDH gene mutation scheduled for induction therapy followed by consolidation therapy. Secondary AML is defined as AML arising after myelodysplastic syndromes (MDSs) or other antecedent hematologic disorders (AHDs) or AML arising after exposure to genotoxic injury including radiation and/or chemotherapy. Subjects may have had previous treatment for MDS or other AHD, including hypomethylating agents (HMAs), provided that the last dose of administration is ?  days prior to study drug initiation
AML associated with inv(); t(;); t(;) or t(;)
Patients who have had prior chemotherapy for AML
>  days since any prior therapy for AML excluding hydroxyurea
A new diagnosis of de novo, secondary or treatment-related AML
Only patients who are relapsed, refractory, or intolerant of standard AML therapy will be eligible for Part  (minimum of  prior line of AML-directed therapy)
Patients with active (blood or bone marrow blasts > %) relapsed or refractory CD+ acute myeloid leukemia (AML) de novo, or secondary. a. Relapsed AML is defined as patients that had a first complete remission (CR) before developing recurrent disease. b. Refractory AML defined as patients that have not achieved a CR after  cycles of induction chemotherapy.
Patients must have newly diagnosed AML or ALL without previous treatment; hydroxyurea will be allowed to control peripheral blast count as clinically indicated but would need to be stopped prior to initiation of tyrosine kinase inhibitor [TKI]); all-trans retinoic acid (ATRA) is permitted during the period prior to ruling out a diagnosis of APL; previous radiation treatment is allowable; patients must be deemed eligible for treatment with cytotoxic induction chemotherapy with cytarabine and idarubicin for AML or hyper-cyclophosphamide, dexamethasone, doxorubicin, vincristine sulfate (CVAD) for ALL; patients newly diagnosed with ALL must have received no prior treatment for their ALL with the exception of steroids (i.e. prednisone, dexamethasone); intrathecal methotrexate or cytarabine, allowed prior to and throughout the enrollment period for AML and ALL
Therapy-related AML (defined as occurrence of AML due to prior exposure to chemotherapy or radiation for malignancy)
Secondary AML (defined as development of AML in patients with an antecedent hematological malignancy)
Diagnosis of AML according to World Health Organization (WHO)  criteria; therapy related AML may be included if in complete response and off treatment for their prior malignancy for more than  years; AML arising after documented myeloproliferative disease (MPD) are excluded
Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:\r\n* Primary refractory non-M AML\r\n** Residual leukemia after a minimum of  prior courses of chemotherapy (same or different)\r\n** Evidence of leukemia recurrence after a nadir bone marrow biopsy demonstrates no evidence of residual leukemia\r\n** Evidence of leukemia after induction therapy which, in the opinion of the investigator, would be appropriate for reinduction with sirolimus/MEC therapy\r\n* Relapsed non-M AML\r\n* Previously untreated non-M AML age >  with no evidence of favorable karyotype defined by presence of t(;)(q;q) [AML-ETO], inversion (inv)(p;q), or t(;)(p;q) [core-binding factor (CBF)beta; myosin, heavy chain (MYH)] by cytogenetics, fluorescence in situ hybridization (FISH), or real time-polymerase chain reaction (RT-PCR)\r\n* Previously untreated secondary AML (from antecedent hematologic malignancy or following therapy with radiation or chemotherapy for another disease) with no evidence of favorable karyotype defined by presence of t(;)(q;q) [AML-ETO], inv(p;q), or t(;)(p;q) [CBFbeta;MYH] by cytogenetics, FISH, or RT-PCR
Patients must have a diagnosis of acute myeloid leukemia (AML) according to World Health Organization (WHO) criteria; therapy-related and secondary AML (arising after a period of myelodysplastic syndrome [MDS]) allowed; prior treatment for MDS with hypomethylator-based therapy and lenalidomide allowed, but not allowed if used after the diagnosis of AML is made, since enrollment to this study is not for relapsed AML
AML secondary to any prior chemotherapy unrelated to leukemia
Recipients with AML in CR must have one of the following:\r\n* Adverse cytogenetics (as evaluated by history) as defined as complex karyotype (>  abnormalities); inv() or t(;); t(;); t(;); monosomy ; trisomy , alone or with an abnormality other than t(;), t(;), inv() or t(;); or t(;)(q;p.)\r\n* Cytogenetically normal AML (CN-AML) with mutations in FMS-like tyrosine kinase  (FLT), deoxyribonucleic acid (DNA) methyl transferase A (DMNTA), or additional sex coombs like  (ASXL)\r\n* Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy\r\n* Secondary AML, defined as AML related to antecedent myeloid neoplasm or cytotoxic chemotherapy\r\n* Hyperleukocytosis, white blood cell (WBC) > ,, at diagnosis
ARM  - AML: Research patients enrolled are those patients with relapsed or refractory CD+ AML de novo, or secondary OR participant who are at high risk for disease recurrence\r\nNOTE: CD+ biphenotypic acute leukemia or CD+ acute lymphoblastic leukemia (ALL) may also be considered but only after discussion with the study principal investigator (PI)\r\n* Relapsed AML is defined as patients that had a first complete remission (CR) before developing recurrent disease (increased bone marrow blasts)\r\n* Refractory AML is defined as patients that have not achieved a first CR after  cycles of induction chemotherapy; for patients with AML evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy
Diagnosis of AML associated with the following karyotypes: inversion (inv)(), t(;), t(;), t(;), or t(;)
For Phase II only: Patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML
Initial diagnosis of poor -risk AML or MDS, treated with either stem cell transplant or cytarabine-based consolidation chemotherapy, within the past - days; the original diagnosis of AML or MDS must have been confirmed by bone marrow aspirate and/or biopsy review by a Johns Hopkins Hospital (JHH) hematopathologist; poor-risk AML is defined as disease that is therapy-related or arises from a previous marrow disorder, or de novo AML that is associated with any of the following characteristics: patient age  years or greater,\r\ntrilineage dysplasia, disease status greater than or equal to second complete remission (CR), fms-related tyrosine kinase  (FLT)/internal tandem duplication (ITD) mutations, detectable disease at time of consolidation chemotherapy or SCT, or poor-risk cytogenetics, which include abnormalities of chromosome , , or , trisomy , q abnormalities, t(;), q-, and complex karyotype
Secondary AML in st remission
AML in st relapse or >= nd remission
Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
Received more than  cycles of induction therapy for AML. Investigational agents as part of front-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see # below).
Adults with AML in need of treatment
Group B: Individuals >  years of age with previously untreated AML or individuals <  years of age with previously untreated AML who refuse or are unable to receive cytarabine as determined by the treating physician
Group C: Cohort CA: Subjects age ?  years with relapsed/refractory AML by WHO criteria; Cohort C: Subjects age ?  years with relapsed/refractory AML with MLL; Cohort C: Subjects with previously untreated AML by WHO criteria and who would have met disease eligibility criteria for Group A or B but refuse or are unable to receive chemotherapy and hypomethylating agent as determined by the treating physician
AML in st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t ;, t;, inv )
Secondary AML in st remission
AML in st relapse or >= nd remission
Patients with therapy-related AML whose prior malignancy has been in remission for at least  months
Patients with relapsed or refractory AML. Relapsed AML is defined as relapse after achieving a response to initial therapy and refractory AML is defined as failure to achieve a response after one previous line of therapy. Response is defined as per IWG criteria (CR, CRi or CRp). Patients who are not candidates to receive or who decline standard of care therapy are also eligible.
AML either de novo or secondary who either :
Prior malignancy (other than basal cell carcinoma and cervical in situ carcinoma) unless treated with a curative intend and without evidence of malignant disease for  year before screening. Patients with prior hematologic malignancies that have progressed to AML (such as Myelodysplastic syndrome, myeloproliferative neoplasms, bi-phenotypic leukemias, AcuteLymphocyticLeukemia) or AML that has relapsed are eligible;
Secondary AML in CR
secondary AML and ALL in st or nd relapse or primary refractory
Patients who have received any therapy other than hydroxyurea with the purpose of treating their AML are not eligible
EXPANSION COHORT: Patients must have a diagnosis of newly diagnosed AML with any of the following:\r\n* Confirmed translocation involving q\r\n* Partial tandem duplication (PTD) of the MLL gene (on q)\r\n* FLT-ITD (internal tandem duplication)\r\n* Increased Fgf in serum ( standard deviations above control serum samples)\r\n* HOX(A/A) over-expression in bone marrow ( standard deviations above control values in CD+ cells from normal subjects)\r\n* Note: Patients with secondary AML are eligible for enrollment into the trial (in both cohorts); secondary AML is defined as AML that has developed in a person with a history of antecedent blood count abnormalities, or myelodysplastic syndromes (MDS), or a myeloproliferative disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or radiation therapy for a disease other than AML
Treatment-related AML and secondary AML in morphological remission (CR or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers
Patients must have relapsed/refractory disease; patients with secondary AML (including those progressing from MDS or myeloproliferative neoplasm [MPN], and those with AML secondary to chemotherapy or radiotherapy for other malignancies) are eligible whether they have received prior therapy for AML or not
Are candidates for and willing to receive intensive IC for their AML.
Have received any prior treatment for AML with the exception of hydroxyurea.
Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve CR or recurrence of AML within  months of achieving CR; relapsed AML is defined as all others with disease after prior remission. (Group B is not currently recruiting. Expected to begin recruiting in rd quarter .)
Specifically, for participants in Cohorts A and A: Treatment nave participants unfit for induction chemotherapy for AML as defined by the following: Age >=  or age  to  years with at least one of the following: ECOG performance status of , Intermediate I/II or adverse risk cytogenetic and molecular alterations per ELN  guidelines or secondary AML, or other comorbidity judged incompatible with intensive chemotherapy
Any approved AML-related therapy within  days prior to enrollment
Patients with secondary AML are eligible for enrollment onto the trial; secondary AML is defined as AML that has developed in a person with a history of antecedent blood count abnormalities, or myelodysplastic syndrome (MDS), or a myeloproliferative disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or radiation therapy for a disease other than AML\r\n* NOTE: Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine is excluded
>=  years of age with AML of any risk classification, or - years of age with high-risk AML disease based on one of the following:\r\n* Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)\r\n* Treatment-related myeloid neoplasms (t-AML/t-MDS)\r\n* AML with FLT-ITD\r\n* Myeloid sarcoma\r\n* AML with multilineage dysplasia (AML-MLD)\r\n* Adverse cytogenetics (defined as -/-q; -/-q; abnormal q, q, q, q, q or p; t(;); t(;); trisomy ; trisomy ; trisomy ; complex karyotypes (>=  clonal abnormalities); monosomal karyotypes
Patients with untreated AML and the presence of FLT mutation (Cohort A only); untreated AML patients >  years who are not candidates for intensive chemotherapy and patients with relapsed or refractory FLT-mutated AML may enroll to Cohort B
Patients with secondary AML or therapy related disease (t-AML) are eligible
Patients with core-binding factor AML (inv[], t[;]) or t(;) (Cohort A only)
AML with favorable risk cytogenetic abnormalities including t(;), t(;) or inv()
Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML) by World Health Organization (WHO) criteria in the blood and/or marrow AND age >=  and not candidates/refuse standard induction treatment OR who have one of the following: poor risk cytogenetics, AML following antecedent hematologic disorder, or therapy-related AML
AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior Myelodysplastic Syndrome (MDS).
Subject must have received no prior treatment for AML with the exception of hydroxyurea
No prior therapy for AML, except for hydroxyurea, in this setting is allowed.
A diagnosis of renal AML >  cm confirmed on pre-enrollment DCE-MRI; a previous diagnosis or treatment of a different AML lesion is allowed
Patients must not have received any prior treatment for AML
Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., inversion , t(;), t(;), t(;)).
Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., inversion , t(;), t(;), t(;)).
Diagnosis of AML according to WHO criteria .
AML (including secondary AML) diagnosed as per WHO criteria
Newly diagnosed, histologically confirmed de novo AML or AML secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)
AML with inv(), t(;), t(;), t(;), or t(;) or molecular evidence of such translocations
AML secondary to exposure to potentially leukemogenic therapies or agents (eg, radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least  years.
For AML patients, no more than  prior salvage therapy.
Patients with AML\r\n* Patients with therapy-related myeloid neoplasms are allowed\r\n* Patients with AML that has evolved from an antecedent hematologic disorder are allowed\r\n* Patients will be eligible regardless of their ultimate plans or candidacy for allogeneic stem cell transplant
AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML)
Subjects >=  years of age with AML who are not candidates for or have refused standard chemotherapy.
Relapsed/refractory AML (>= % blasts in bone marrow or extramedullary leukemia) or newly diagnosed AML patients who are not candidates for (age >=  years; adverse cytogenetics, e.g., as defined by the Medical Research Council [MRC] Prognostic Groupings; secondary AML; organ dysfunction arising from significant co-morbidities not directly linked to leukemia; Eastern Cooperative Oncology Group [ECOG] = ) or not willing to undergo intensive chemotherapy; Note that both relapsed/refractory and newly diagnosed AML patients will be eligible for the dose escalation part of the study, but only newly diagnosed patients will be eligible for the dose expansion cohort
Patients with previously untreated AML with core binding factor (CBF) chromosomal aberrations (inv[]/t[;] or t[;]); Note that patients with relapsed or refractory AML with CBF chromosomal aberrations will be eligible
Subject has received previous therapy for AML, with the exception of the following:
Subject has clinically significant coagulation abnormality unless secondary to AML.
Diagnosis of AML (AML de novo and post-MDS) or DLBCL
Diagnosed with AML
Patients with secondary AML or therapy related disease (t?AML) are eligible; patients who received decitabine or ?azacytidine as prior treatment for myelodysplastic syndrome (MDS) or AML remain eligible; however, none of these agents is permitted within  months of study entry
We will define patients as high risk AML and thus eligible if they meet one or more of the following criteria:\r\n* Secondary AML (from underlying MDS or therapy related)\r\n* Presence of complex cytogenetic abnormalities (>=  cytogenetic abnormalities), all monosomies, del q, del q, inv, t(;), t(;), t(;), abn q (excluding t[;])\r\n* Fms-related tyrosine kinase  (FLT)-internal tandem duplication (ITD) mutation positive\r\n* Age >=  years
Subject has received previous therapy for AML, with the exception of the following:
Patients with AML must have either: (a) relapsed or refractory leukemia after receiving at least one prior conventional induction therapy. Those in early first relapse must not have a matched donor and/or they must not be a candidate for allogeneic stem cell transplantation (usually this would mean the patient is too ill, obese, has a co-morbid condition or is over the age of  years) or (b) poor-risk AML as defined below: (i) Treatment related AML, except if it is associated with favorable cytogenetics (e.g., inversion , t(;), t(;), t(;), and not a candidate for stem cell transplantation, or (ii) AML with an antecedent hematologic disease (e.g., MDS, myelofibrosis, polycythemia vera, etc.), and not a candidate for stem cell transplantation. (iii) De novo AML >  years of age. (iv) AML with unfavorable cytogenetics regardless of age (> years), if patients are not candidates for allogeneic transplantation. Unfavorable cytogenetics are the following: complex (> abnormalities), -, -, q-, q-, abnormalities of q excluding t(;), t(;), inversion , t(;), t(;). (c) Patients older than  years of age who had AML (i.e., > % bone marrow blasts) and no prior therapy for AML
Patients with previously untreated AML are candidates if they are unable to receive anthracyclines, and have documented AML with >= % blasts within one week prior to enrollment
Newly diagnosed AML (according to the World Health Organization [WHO]  classification) except t(;), including:\r\n* De novo AML\r\n* Secondary AML\r\n* Secondary AML arising from previously diagnosed myelodysplastic syndromes (MDS) or other antecedent hematologic malignancy treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) (i.e., decitabine or azacitidine)
Patients must have one of the following disease characteristics:\r\n* Therapy-related myeloid neoplasm (t-MN) age >=  years\r\n** Patients must have received cytotoxic chemotherapy, radiation, or a drug known to affect the properties of deoxyribonucleic acid (DNA) or cell growth, prior to current diagnosis of t-MN; this broad definition is meant to include any prior therapy with chemicals that affect DNA replication, DNA integrity, or DNA structure, or chemicals that alter cell growth; this includes traditional cytotoxic chemotherapy, newer immunologic agents that have been shown to have cytotoxic activities in addition to immunosuppressive functions, and other chemicals; note that patients with primary AML could be diagnosed with a t-MN if morphology/cytogenetic analysis clearly indicated that the second process is not a relapse of the original disease\r\n* AML arising from an antecedent hematological disorder age >=  years\r\n* De novo AML in patients age >=  years\r\n* Relapsed and/or refractory AML >=  years
Investigator considers patient ineligible for intensive remission induction therapy based on documented medical reasons (e.g. disease characteristics like AML genetics, type of AML (de novo or secondary), and patient characteristics like performance score, concomitant diagnoses, organ dysfunctions).
Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease
Prior treatment intended for induction therapy of AML; only hydroxyurea is permitted for control of blood counts. For example, a patient with MDS that changes HMA dose and schedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabine alone (>g/m/day) or cytarabine plus an anthracycline as well as prior HSCT are also excluded.
Confirmed primary AML relapsed or refractory after prior therapy, AML secondary to antecedent chemotherapy or radiation therapy, or AML due to prior myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) as defined by WHO criteria with presence of either FLT ITD and/or other FLT activating mutations
Patients with secondary AML should have failed no more than two () prior regimens
AML that is considered to be therapy-related
Relapsed AML or secondary AML (from myelodysplastic syndromes [MDS] or treatment related): not in CR after  or more cycles of standard re-induction therapy
AML relapsed >  months after transplant
Male or female patient ?  years of age with newly diagnosed, histologically confirmed, AML including de novo, secondary to antecedent hematologic disorders, or treatment-related disease with intermediate or unfavorable-risk cytogenetics
Previous chemotherapy for AML except for the following, which are allowed:
Patients with AML at initial diagnosis or at first relapse
For subjects Age < \r\n* Refractory AML\r\n* OR AML relapse within six months of attaining remission\r\n* OR AML relapse more than six months after achieving a remission, who cannot achieve a second remission \r\n* OR Untreated subjects who develop AML after preexisting hematologic disease \r\n* OR Secondary AML\r\nFor subjects Age >= \r\n* De novo AML not candidates for induction chemotherapy\r\n* OR Refractory AML\r\n* OR AML relapse within six months of attaining remission\r\n* OR AML relapse more than six months after achieving a remission, who cannot achieve a second remission\r\n* OR Untreated subjects who develop AML after preexisting hematologic disease \r\n* OR Secondary AML
Recipients with AML in first complete remission (CR) must have one of the following:\r\n* Adverse cytogenetics with residual disease detectable by flow cytometry, cytogenetic analysis, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR); adverse cytogenetics in AML are defined as complex karyotype (>=  abnormalities); inversion (inv)() or t(;); t(;); t(;); monosomy ; trisomy , alone or with an abnormality other than t(;), t(;), inv() or t(;); or t(; (q;p.) \r\n* Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy \r\n* Secondary AML, defined as AML related to antecedent MDS, MPD, or cytotoxic chemotherapy\r\n* Hyperleukocytosis, white blood cells (WBC) >= ,, at diagnosis\r\n* Mutations in the FMS-like tyrosine kinase  (FLT) gene (FLT-LM; FLT internal tandem duplication [ITD]s)
Patients must have histologically confirmed relapsed or refractory AML and meet the following criteria:\r\n* Relapsed disease is defined as AML is in st or greater marrow relapse\r\n* Refractory disease is defined as AML which failed to go into remission after st or greater relapse, OR AML which failed to go into remission after two or more induction attempts from original diagnosis
AML associated with favorable risk karyotypes including inv(), t(;), t(;), or t(;)
Secondary AML
The original diagnosis of AML must have been confirmed by bone marrow aspirate and/or biopsy review by a Johns Hopkins (JH) hematopathologist; patients are eligible if they have AML that is not classified as poor-risk or APL; poor-risk AML is defined as therapy-related, arising from a previous marrow disorder, or de novo AML associated with any of the following characteristics: trilineage dysplasia, fms-related tyrosine kinase  (FLT)/internal tandem duplication (ITD) mutation, poor risk cytogenetics including: chromosome , , or  abnormalities, t(;), and complex karyotype
Histologically proven non-M AML:\r\n* Refractory/relapsed AML OR\r\n* Initial diagnosis of AML in patient >=  years old
Have an unequivocal histologic diagnosis of acute myeloid leukemia (AML) (including secondary AML)
No prior therapy for AML except hydroxyurea to control counts
RR-AML
Patients with secondary AML or therapy related disease (t-AML) are eligible
Diagnosed with AML according to the WHO  classification. Note: subjects with secondary AML following Myelodysplastic syndrome or secondary to previous leukemogenic therapy are allowed provided that a record of previous MDS history or leukemogenic therapy history is available.
Previous AML treatment (other than hydroxyurea).
Patients diagnosed with AML meeting one of the following criteria:\r\n* Newly diagnosed, age  and older\r\n* High risk cytogenetics and molecular abnormalities (National Comprehensive Cancer Network [NCCN] criteria)\r\n* Relapsed or refractory to prior chemotherapy\r\n* Secondary AML
Patient must not have received definitive treatment for AML, defined as any prior chemotherapy with antileukemic activity
The patient has a diagnosis of AML associated with karyotype t(;).
Patients with FLT ITD positive AML or AML patients with other cytogenetic abnormalities who are eligible for trials of other targeted investigational agents from which the investigator feels there is greater benefit.
Morphologically documented primary AML, prior-chemotherapy-related AML or AML secondary to an antecedent hematologic disorder (e.g., Myelodysplastic Syndrome) as defined by WHO criteria, confirmed by pathology review. For Cohort Expansion Phase (Part ) only: Bone marrow involvement is required.
Have either relapsed or refractory AML, or who have newly diagnosed Flt-ITD positive AML but either refuse or are considered by the Investigator not to be an appropriate candidate for standard chemotherapy.
+ yrs with AML not eligible for standard frontline chemo
The leukemia is a de novo or secondary AML.
The patient has cytologically proven AML, as defined by the WHO classification. The pretreatment AML karyotype should be documented.
The leukemia could be a de novo or secondary AML.
Hospitalized patients with high-risk AML, defined as:\r\n* Newly diagnosed patients with AML \r\n* Newly diagnosed AML with antecedent hematologic disorder\r\n* Newly diagnosed therapy-related AML\r\n* Relapsed AML\r\n* Primary refractory AML
Patients must have one of the following diagnoses and/or treatment plans:\r\n* Newly diagnosed de novo AML\r\n* First or subsequent relapse of AML\r\n* Secondary AML\r\n* Treatment with institutional standard AML therapy in those without AML (for example, myelodysplastic syndrome, bone marrow blasts > % or biphenotypia)\r\n* Note: Patients with a history of prolonged antifungal therapy (example, relapsed AML) are eligible
Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;
Prior treatment for AML, except for the following allowances:
Previous chemotherapy for AML
Patients with secondary or relapsed AML or APL should be excluded
Patients with advanced AML that harbors IDH mutation
Patients must have AML at initial diagnosis or at first relapse
Participants with AML must either refuse or not be considered candidates for intensive induction chemotherapy. Previously treated participants should have evidence of persistent or recurrent AML in the peripheral blood and/or bone marrow. Participants must have white blood cell (WBC) <  x ^cells/L.
diagnosis of AML
Prior chemotherapy for AML