Patients with de novo MDS who have, or have previously had, Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is NOT a requirement.
International prostate symptom score (IPSS) of < 15 21 days prior to registration
Patients with MDS must have failed to respond to, or progressed after, adequate treatment with a hypomethylating agent (HMA), or had documented intolerance of an HMA, and must have an International Prognostic Scoring System (IPSS) score ? 1.5
MDS patients must have Intermediate (>3 to 4.5 points), High Risk (>4.5 - 6) or Very High Risk (>6 points) disease according to the Revised International Prognostic Scoring System 2012.
Documented diagnosis of MDS according to World Health Organization (WHO) criteria that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease at screening as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) and who are refractory to or are not amenable or eligible for approved MDS therapy. The second expansion cohort will enroll patients with low or intermediate-1 risk MDS with symptomatic anemia, who, experienced ESA treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment and who have not received prior HMA and/or lenalidomide.
Patient with IPSS category of Int-2 or high-risk MDS.
Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification or MDS with an International Prognostic Scoring System (IPSS) risk category of Intermediate 2 or High Risk
Diagnosis of primary MDS classified as very low, low or intermediate risk with <5% blasts of >= 16 weeks duration
Relapsed or refractory myelodysplastic syndrome (MDS), International Prognostic Scoring System intermediate or high-risk, with no available therapies
Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients
Risk category very low, low or intermediate (Revised International Prognostic Scoring System, IPSS-R)
Group B: Subjects with relapsed or refractory AML, Subjects with relapsed or refractory high-risk MDS, defined as revised International Prognostic Scoring System (IPSS-R) intermediate or greater disease.
Myelodysplastic syndrome (MDS) with intermediate or high-risk IPSS or equivalent IPSS-R score with < 10% blasts in the bone marrow
Diagnosis of MDS (de novo or secondary) by bone marrow biopsy based on the World Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS using the IPSS (International Prognostic Scoring System)
Diagnosis of MDS by bone marrow biopsy of Intermediate-2 and High risk category MDS based on the WHO classification using the IPSS (International Prognostic Scoring System)
MDS should be classified as:\r\n* Intermediate 3+ or higher risk according to the revised international prognostic scoring system (IPSS-R)
INCLUSION CRITERIA\n\n          1. Written informed consent obtained prior to any screening procedures and in accordance\n             with federal, local, and institutional guidelines.\n\n          2. Age ? 18 years.\n\n             Higher Risk Myelodysplastic Syndrome (Part F):\n\n          3. Documented diagnosis of MDS with 5-19% myeloblasts.\n\n          4. Patients should be intermediate-2 or high-risk MDS by International Prognostic Scoring\n             System (IPSS).\n\n          5. Patients believed to be IPSS high risk, without clearly meeting IPSS categories above\n             should be discussed with the medical monitor prior to enrolling.\n\n          6. HMA refractory patients including:\n\n               1. ? 2 cycles of azacitidine and/or decitabine or experimental agents (such as\n                  SGI-110 or ASTX727 or similar) with clear progressive disease (PD) (no count\n                  recovery with ?50% increase in bone marrow blasts)\n\n                  OR\n\n               2. ? 4 cycles of azacitidine and/or decitabine (or other hypomethylating therapy)\n                  with lack of improvement (no CR/CRi/PR/HI).\n\n          7. Patients receiving a stable dose of erythropoiesis-stimulating agent (ESA) for at\n             least 1 month at the time of study entry may continue to receive ESA.\n\n        EXCLUSION CRITERIA\n\n        Patients in All Parts of the Study:\n\n          1. Major surgery within 4 weeks before C1D1.\n\n          2. Impaired cardiac function or clinically significant cardiac diseases.\n\n          3. Uncontrolled active severe systemic infection requiring parenteral antibiotics,\n             antivirals, or antifungals within one week prior to C1D1.\n\n          4. Patients with known symptomatic brain metastasis.\n\n          5. Prior malignancies:\n\n               1. Patients in All Parts of the Study: Patients with adequately resected basal or\n                  squamous cell carcinoma of the skin, or adequately resected carcinoma in situ\n                  (i.e. cervix) may enroll irrespective of the time of diagnosis.\n\n               2. Patients with Higher Risk MDS only: Concomitant malignancies or previous\n                  malignancies with less than a 1-year disease free interval at the time of\n                  enrollment.\n\n             INDICATION-SPECIFIC EXCLUSION CRITERIA\n\n             Higher risk Myelodysplastic Syndrome (Part F):\n\n          6. IPSS low or intermediate-1 risk MDS.\n\n          7. Evidence of transformation to AML by World Health Organization (WHO) (?20% blasts in\n             bone marrow or peripheral blood).\n\n          8. Patients receiving granulocyte-colony stimulating factor (G-CSF) or granulocyte\n             macrophage-colony stimulating factor (GM-CSF) within the 3 weeks prior to C1D1.
high risk group MDS, according to IPSS Risk Stratification (Norway Only) Part B:
high/intermediate (int-2) risk group MDS, according to IPSS Risk Stratification (Norway Only)
High-risk MDS/CMML (defined as ? 10% peripheral blood or marrow blasts and/or IPSS score ? 1.5) and relapsed or refractory to prior therapy
Patients must have International Prognostic Scoring System (IPSS) categories of low- or intermediate-1-risk disease
Intermediate-2 or high-risk disease per IPSS
Myelodysplastic syndrome (MDS)/myeloproliferative disorders (MPD) other than myelofibrosis: \r\n* International prognostic scoring system (IPSS) risk score of INT-2 or high risk at the time of diagnosis.\r\n* Any IPSS risk category if life-threatening cytopenia(s) exists.\r\n* Any IPSS risk category with karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia.\r\n* MDS/ myeloproliferative disorder overlap syndromes without myelofibrosis.\r\n* MDS/MPD patients must have less than 10% bone marrow myeloblasts and ANC > 0.2 (growth factor supported if necessary) at transplant work-up.
Pathologically proven acute myeloid leukemia (AML) or intermediate, high-risk, or very high risk Myelodysplastic Syndrome (MDS) as defined by the World Health Organization (WHO) criteria or Revised International Prognostic Scoring System (IPSS-R) which is relapsed or refractory (R/R) to standard therapy and/or for which standard therapy is contraindicated or which has not adequately responded to standard therapy.
(Arm A only): Subjects with high-risk MDS (i.e. International Prostate Symptom Score [IPSS] intermediate-2 or high-risk; or revised [R]-IPSS high or very-high risk). Patients with intermediate-1 risk by IPSS or intermediate risk by R-IPSS with high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
Have a confirmed diagnosis of:\r\n* International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2 or high-risk MDS including chronic myelomonocytic leukemia (CMML) OR\r\n* Low blast count AML with =< 30% blasts previously classified as refractory anemia with excess blasts in transformation and, who have not been previously treated with a hypomethylating agent
Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):
MDS classified as intermediate 1-risk or high risk according to the international prognostic scoring system (IPSS) or revised-IPSS
Intermediate 1 (INT-1) or higher risk MDS defined by International Prognostic Scoring System (IPSS) criteria
Subjects with high-risk MDS (i.e. International Prognostic Scoring System [IPSS] Intermediate-2 or high-risk; or R-IPSS high or very-high risk). Patients with Intermediate-1 risk by IPSS or Intermediate risk by R-IPSS and with IDH1 or IDH2, or high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
MDS with International Prognostic Scoring System (IPSS) intermediate-2 or higher, therapy-related MDS or chronic myelomonocytic leukemia (CMML)
Have very low, low or intermediate-risk disease by the Revised International Prognostic Scoring System (IPSS-R)
Pathologically confirmed disease as follows:\r\n* AML patients who either have: \r\n** Relapsed or refractory disease after receiving one or more courses of induction chemotherapy, hypomethylating agent therapy, or bone marrow transplant or \r\n** De novo AML but not deemed to be a candidate for conventional therapy based on age, co-morbidities, or patient preference\r\n* MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) with high risk features as defined below who have relapsed after initial response or are refractory (failure to achieve a complete response [CR], partial response [PR], or hematologic improvement [HI]) after receiving at least 4 cycles of hypomethylating agents 5-azacitidine or decitabine +/- other therapies +/- bone marrow transplant OR with de novo MDS but have refused to receive hypomethylating therapy: \r\n** Intermediate (INT)-2 or high International Prognostic Scoring System (IPSS) score OR high or very high Revised International Prognostic Scoring System (IPSS-R) or\r\n** Secondary MDS (defined as MDS developing in a patient with an antecedent hematologic disorder or any patient with prior chemotherapy or radiation exposure) or\r\n** INT-1 IPSS or intermediate R-IPSS MDS with excess blasts (>= 5% blasts in bone marrow [BM]) or transfusion-dependency or\r\n** MDS progressing to oligoblastic AML with 21-30% BM blasts or\r\n** CMML or MDS/MPN with >= 5% marrow blasts, transfusion-dependency, abnormal karyotype, or proliferative features (white blood cell count >= 13,000/uL, splenomegaly on physical examination, or extramedullary disease)
Myelodysplastic syndrome (MDS): Primary or therapy related, including patients that will be considered for transplant; these include any of the following categories: 1) revised International Prognostic Scoring System (IPSS) intermediate and high risk groups, 2) malondialdehyde (MDA) with transfusion dependency, 3) failure to respond or progression of disease on hypomethylating agents, 4) refractory anemia with excess of blasts, 5) transformation to acute leukemia, 6) chronic myelomonocytic leukemia, 7) atypical MDS/myeloproliferative syndromes, 8) complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p)
Myelodysplasia (MDS) requiring transplant as defined as: International Prognostic Scoring System (IPSS) intermediate 2 (INT-2) or high risk; revised (R)-IPSS high or very high; World Health Organization (WHO) classification: refractory anemia with excess blasts (RAEB)-1, RAEB-2; severe cytopenias: absolute neutrophile count (ANC) < 0.8, anemia or thrombocytopenia requiring transfusion; poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS; blasts must be < 5% by bone marrow aspirate morphology
Has one of the following diagnoses: Subjects must have refractory or relapsed AML or ALL, CML in blast phase, or high risk MDS (defined by Revised International Prognostic Scoring System [IPSS-R] score as High or Very High for inclusion in Part 1 of the study. Subjects must have refractory or relapsed AML or high-risk MDS (defined by IPSS-R score as High or Very High for inclusion in Part 2 of the study.
Myelodysplastic syndromes (MDS), intermediate-1 (INT-1), intermediate-2 (INT-2) or high Revised International Prognostic Scoring System (IPSS-R) score that has failed at least 1 first line therapy
Patients with higher risk MDS (International Prognostic Scoring System [IPSS] int-2 or high; or >= 10% blasts as defined by World Health Organization [WHO])\r\n* No prior intensive chemotherapy or high-dose cytarabine (>= 1 g/m^2)\r\n* Prior biologic therapies (=< 1 cycle of prior decitabine or azacitidine), targeted therapies, or single agent chemotherapy is allowed\r\n* Off chemotherapy for 2 weeks prior to entering this study with no toxic effects of that therapy, unless there is evidence of rapidly progressive disease\r\n* Hydroxyurea is permitted for control of counts prior to treatment\r\n* Hematopoietic growth factors are allowed
Patients with a diagnosis of AML, acute biphenotypic leukemia, or high risk MDS (>= 10% blasts or International Prognostic Scoring System [IPSS] >= intermediate-2) will be eligible; patients with CML in myeloid blast phase are also eligible
Patients with myelodysplastic syndromes (MDS): a. de novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores; patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy, or b. patients with treatment-related MDS
RECIPIENT: Clinical history of at least one life-threatening infection and/or MDS with International Prognostic Scoring System (IPSS) category of intermediate-1, intermediate-2, or high
Myelodysplastic syndromes with intermediate, high or very high risk Revised International Prognostic Scoring System (R-IPSS) score, chronic myelomonocytic leukemia (CMML) or therapy related myelodysplastic syndromes (MDS)
PHASE II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System
Patients with the diagnosis of MDS (low, int-1 by International Prognostic Scoring System [IPSS], or hypocellular) who are either previously treated or untreated are eligible for this trial
International Prognostic Scoring System (IPSS) risk categories Int-2 or High (IPSS overall score ? 1.5) and
Participant has a diagnosis other than previously untreated de novo MDS with IPSS risk categories Int-2 or High, including:
MDS with IPSS risk categories Low or Int-1 (overall IPSS score < 1.5)
MDS with at least one of the following poor-risk features: \r\n* Poor-risk cytogenetics (7/7q minus or complex cytogenetics)\r\n* International Prognostic Scoring System (IPSS) score of intermediate (INT)-2 or greater; treatment-related MDS\r\n* MDS diagnosed before age 21 years \r\n* Progression on or lack of response to standard deoxyribonucleic acid (DNA)-methyltransferase inhibitor therapy \r\n* Life-threatening cytopenias, including those generally requiring greater than weekly transfusions
Myelodysplastic syndrome (MDS): \r\n* Intermediate-1 International Prognostic Scoring System (IPSS) score with poor risk cytogenetics as defined by IPSS\r\n* Intermediate-2 or High International Prognostic Scoring System (IPSS) score\r\n* MDS/ myeloproliferative disorder overlap syndromes\r\n* Any score with life threatening cytopenia(s), including red cell or platelet transfusion dependence\r\n* Receipt of at least one cycle of cytotoxic chemotherapy, azacitidine or decitabine\r\n* MDS patients must have =< 5% bone marrow myeloblasts and absolute neutrophil count (ANC) >= 0.2 (growth factor supported if necessary) at transplant work-up
Patient has newly diagnosed AML and refuses or is not eligible for treatment with aggressive chemotherapy and/or SCT; OR AML and has relapsed or been refractory to prior therapy; OR High-risk MDS, defined as IPSS intermediate-2 (INT-2) or IPSS high-risk, and refuses or is not eligible for standard or aggressive chemotherapy and SCT or prior experimental therapies; OR High-risk MDS, defined as IPSS INT-2 or IPSS high risk, and has failed or been refractory to deoxyribonucleic acid (DNA) hypomethylating agents (azacitidine or decitabine), lenalidomide, standard/aggressive chemotherapy, SCT, or prior experimental therapies.
MDS and >5% blasts, or IPSS risk group intermediate-1, intermediate-2 or high risk
Must have histologically or cytologically confirmed diagnosis of MDS according to WHO classification that meets IPSS low to intermediate-1 risk criteria.
International Prognostic Scoring System (IPSS)-revised (R) intermediate, high or very high risk disease
Histologic confirmation of one of the following:\r\n* Myelodysplastic syndrome (MDS) fulfilling all the criteria below:\r\n** International Prognostic Scoring System (IPSS) intermediate-2 or high risk MDS; or Revised International Prognostic Scoring\r\nSystem (IPSS-R) intermediate, high, or very high risk MDS \r\n** Relapsed/refractory disease\r\n** Requiring therapy based on the presence of one or more cytopenias (hemoglobin [Hb] < 10 g/dL and/or red cell transfusion dependence, platelets < 50,000/uL, or absolute neutrophil count [ANC] < 1,000/ uL) or excess blasts (>= 5% in the peripheral blood or bone marrow)\r\n* Myelodysplastic/myeloproliferative Neoplasm (MDS/MPN) as defined by the World Health Organization (WHO) criteria, including chronic myelomonocytic leukemia (CMML), atypical chronic myelogenous leukemia (CML), and MDS/MPN-unclassifiable fulfilling the criteria listed below\r\n** Relapsed/refractory disease\r\n** Requiring therapy based on the presence of one or more cytopenias (Hb < 10 g/dL and/or red cell transfusion dependence, platelets < 50,000/uL, or ANC < 1,000/ uL), excess blasts (>= 5% in the peripheral blood or bone marrow), or palpable splenomegaly or\r\n** Previously untreated subsets (e.g atypical CML, MDS/MPN unclassifiable) requiring therapy as defined above and in whom no approved therapies exist\r\n* Myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis fulfilling the criteria listed below:\r\n** Intermediate-2 or high risk disease according to the Dynamic International Prognostic Scoring System (DIPSS) classification\r\n** Refractory or intolerant to JAK inhibitor therapy, or deemed - ineligible for ruxolitinib therapy due to pre- existing cytopenias (thrombocytopenia < 50,000/uL, anemia hemoglobin < 9 g/dL or red cell transfusion dependence); requiring further therapy based on the presence of one or more cytopenias (Hb < 10 g/dL and/or red cell transfusion dependence, platelets < 50,000/uL, or ANC < 1,000/uL), excess blasts (>= 5% in the peripheral blood or bone marrow), or palpable splenomegaly
Classified as high or very high risk according to the Revised International Prognostic Scoring System (IPSS-R) risk category.
IPSS (International Prostate Symptom Score) =< 20
IPSS-R risk category of Intermediate, High, or Very High assessed at screening
MDS classified as Low-risk or Int-1 risk or Int-2 risk according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as High-risk since their MDS was diagnosed.
Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all International Prognostic Scoring Systems (IPSS) categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics; blasts must be less than 5%; if >= 5% requires therapy (induction or hypomethylating agents) pre-transplant to decrease disease burden
High risk myelodysplastic syndrome (MDS)\r\n* Intermediate II and high risk by International Prognostic Scoring System (IPSS)\r\n* Intermediate, high, or very high by World Health Organization (WHO) classification-based Prognostic Scoring System (WPSS)\r\n* Transfusion dependent\r\n* Therapy-related MDS or MDS evolved from previous hematological disorder (excepting myelofibrosis)
International Prostate Symptom Score (IPSS) > 15
Central confirmation of the categorization of the MDS risk classification, as per the Revised - International prognostic scoring system (IPSS-R) Intermediate risk with >10% blasts or poor or very poor cytogenetics, or IPSS-R High or Very High risk (Results of central pathology review required prior to receiving the first dose of IP). Acute myeloid leukemia (AML) Cohort:
Patient must have IPSS categories of low- or intermediate-1-risk disease; patients must have IPSS score determined by cytogenetic analysis prior to randomization; patients must have cytogenetic analysis done (to calculate IPSS); if the current bone marrow biopsy is a dry tap, patients with cytogenetic failure and < 10% marrow blasts will be eligible; subjects with cytogenetic failure must have previous cytogenetic results (fluorescence in situ hybridization [FISH] is not a substitute) within the last 6 months post last type of MDS treatment (in this case, not referring to growth factors as type of MDS treatment)
Diagnosis of acute myeloid leukemia (AML) or high or very high-risk MDS by International Prognostic Scoring System revised for whom transplant is recommended
For MDS; International Prognostic Scoring System (IPSS)-revised criteria of high or very high at diagnosis
If the patient has been diagnosed with MDS, disease of patient must be classified as Int-1, Intermediate-2 (Int-2) or High-risk, according to International Prognosis Scoring System (IPSS) classification. Note: Only Int-2 or High-risk patients will be enrolled at French site.
International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk MDS
For MDS and CMML participants, prognostic risk category, based on the Revised International Prognostic Scoring System (IPSS R), of:
Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS)
International Prostate Symptom Score (IPSS) 20 or less
Classified as high risk OR intermediate-2 risk as defined by the International Prognostic Scoring System (IPSS) for PMF, or intermediate-1 risk (IPSS) associated with symptomatic splenomegaly, hepatomegaly, anemia (hemoglobin < 10.0 g/dL), and/or unresponsive to available therapy
Patients with previously treated low or intermediate-1 risk MDS by the International Prognostic Scoring System (IPSS) classification
Previously untreated low or intermediate-1 risk MDS patients
Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with de novo MDS who have or have previously had Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is not a requirement; Subjects must have < 20% bone marrow blasts, assessed within 60 days of informed consent; Subjects may have received prior therapy for the treatment of MDS prior to enrollment
International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS
One of the following diagnoses:\r\n* MDS with International Prognostic Scoring System (IPSS) score of INT-1 or higher and one of the following:\r\n** Symptomatic anemia with either hemoglobin < 10.0 g/dL or requiring red blood cell (RBC) transfusion\r\n** Thrombocytopenia with a history of two or more platelet counts < 50,000/uL or a significant hemorrhage requiring platelet transfusions\r\n** Neutropenia with two or more absolute neutrophil count (ANC) < 1,000/uL\r\n* Non-M3 AML
Patients must have disease that requires therapy, including intermediate-1, intermediate-2, or high-risk disease according to the International Prognostic Scoring System (IPSS) or Dynamic-IPSS
Patients with MDS (up to 20% blasts) of any risk; patients with lower risk MDS (low and intermediate [int]-1 by International Prognostic Scoring System [IPSS]) could have received prior non-hypomethylating agent therapy (i.e. growth factors or lenalidomide); patients with higher risk MDS (int-2 or high by IPSS) should not have received prior therapy with a hypomethylating agent
Has severe voiding symptoms (International Prognostic Scoring System [IPSS] > 20) or urinary retention requiring a catheter
IPSS low, intermediate -1, intermediate-2, or high risk MDS (including CMML) in Dose Escalation and Dose Confirmation-Randomization; only intermediate-2, or high risk MDS in Dose Confirmation-Open Label
Patients must have histologically or cytologically confirmed: \r\n* Pathologically confirmed intermediate or poor risk newly diagnosed AML (subtypes M0, 1, 2, 4-7), but excluding newly diagnosed core-binding factor (CBF) (t(8;21) or M4eo subtype (inv(16) or t(16;16) AMLs and acute promyelocytic leukemia (acute promyelocytic leukemia [APL], M3)\r\n* MDS with high risk features as defined by intermediate (INT)-2 or high International Prognostic Scoring System (IPSS) score with > 10% blasts in the bone marrow\r\n* Chronic myelomonocytic leukemia-2 (CMML-2) defined as having > 10% blasts (including promonocytes) in the bone marrow or 5-19% blasts (including promonocytes) in the peripheral blood
Advanced MDS by virtue of intermediate-2 or high-risk MDS by International Prognostic Scoring System (IPSS) score, or high or very-high risk by IPSS-revised (R)
Diagnosis of myelodysplastic syndrome and one of the following:\r\n* Cytopenias requiring red blood cell and/or platelet transfusions or neutropenia (absolute neutrophil count [ANC] < 1 x 10^9/L)\r\n* International Prognostic Scoring System (IPSS) score of intermediate-1 (INT-1) or higher at screening\r\n* MDS with excess blasts in transformation as defined by French-American-British (FAB) criteria (20-29% bone marrow blasts) or\r\n* Chronic myelomonocytic leukemia
Low, intermediate-1, intermediate-2 or High-risk category by IPSS
Revised International Prognostic Index score of >=1
De novo or secondary International Prognostic Scoring System (IPSS) low- or intermediate-1- risk myelodysplastic syndromes (MDS), including chronic myelomonocytic leukemia (CMML)
Patients must have one of the following hematologic malignancies: \r\n* AML any stage and cytogenetic risk-group with the only exception being that patients with AML and favorable cytogenetics t(8;21), inv 16, or t(15;17) who achieve complete remission with one course of induction chemotherapy are not eligible; \r\n* MDS with intermediate or high risk International Prognostic Scoring System score (IPSS scores) or treatment related MDS; patients with low risk MDS are eligible if they fail to respond to hypomethylating agent therapy such as azacitidine or decitabine
Patients with advanced myelodysplastic syndromes (MDS), including those with International Prognostic Scoring System (IPSS) Int-2 and high-risk disease with less than 10% marrow blasts and no circulating myeloblasts after most recent therapy. Patients with acute leukemia that develops from a pre-existing MDS must meet the inclusion criteria for patients with AML detailed above.
All prognostic risk groups according to the International Prostate Symptom Score (IPSS) and MD Anderson Risk Model
IPSS =< 20
Patients must weigh between 35-135 kg MDS low -int-1 risk as determined by IPSS score and confirmed by bone marrow examination within 6 months prior to study entry
Myelodysplastic syndromes with International Prognostic Scoring System score (IPSS score) >= 2 or myelodysplasia that has not responded to chemotherapy
Myelodysplasia (MDS)/myeloproliferative syndrome (MPS) - (> intermediate 1 [int-1] per International Prognostic Scoring System [IPSS]) after > or = 1 prior cycle of induction chemotherapy; must have < 5% marrow blasts at time of transplant
Patients with a histologically confirmed diagnosis of myelodysplastic syndrome (MDS) by World Health Organization (WHO) classification, and lower-risk MDS as defined by the International Prostate Symptom Score (IPSS) classification (low or intermediate [int]-1 disease) or Revised-International Prostate Symptom Score (R-IPSS) classification (very low or low) are eligible; patients with MDS/myeloproliferative neoplasm (MPD) overlap syndromes including chronic myelomonocytic leukemia (CMML) are also eligible if they have low or int-1 disease per IPSS; patients may have received MDS-directed therapy (i.e. lenalidomide), although patients with prior exposure to hypomethylating agents (e.g. 5-azacitidine or decitabine) are not eligible
Patients must have a history of de novo or therapy-related AML (defined by World Health Organization [WHO] classification of >= 20% bone marrow blasts) or high-risk MDS (defined by International Prognostic Scoring System [IPSS] or Revised International Prognostic Scoring System [IPSS-R])
Intermediate 1, intermediate 2 or high risk MDS by IPSS
International prognostic score-revised (IPSS-R) of >3.5 (Intermediate, High or Very High)
Previously untreated AML (>= 20% blasts) or AML M6; patients with high-risk (intermediate-2 or\r\nhigh by International Prognostic Scoring System [IPSS] or >= 10% blasts) MDS will also be eligible; prior therapy with hydroxyurea, biological or targeted therapy (e.g. fms-related tyrosine kinase 3 [flt3] inhibitors, other kinase inhibitors, azacitidine), or hematopoietic growth factors is allowed; no prior chemotherapy is allowed except for a single or a two day dose of cytarabine (up to 3 g/m^2) for emergency use is also allowed as prior therapy
Diagnosis of newly diagnosed AML (other than acute promyelocytic leukemia [APL]) or high-risk (intermediate-2 high by International Prognostic Scoring System [IPSS] or > 10% blasts, including chronic myelomonocytic leukemia [CMML]) MDS; prior therapy with Hydrea and the use of a single or a two day dose of cytarabine (up to 3 g/m^2) for emergency use up to 24 hours prior to start of study therapy is allowed; prior therapy for MDS or other antecedent hematologic disease (AHD) is not allowed
Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS)
Patients with MDS (IPSS score ? 1.5)
Classification by the International Prognostic Scoring System (IPSS) as low or intermediate-1 risk MDS according to cytogenetics, blood cytopenias and % bone marrow blasts within 28 days of the first dose of treatment in this study
WHO-confirmed MDS, with an International Prognostic Scoring System (IPSS) score of > 1.0 (defined as intermediate 2 or high-risk)
Documented diagnosis of myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), White blood cells (WBC) ? 13,000 /mm3, World Health Organization (WHO)) that meets International Prognostic Scoring System (IPSS) criteria for low or intermediate-1 risk disease
International Prognostic Scoring System (IPSS) low- or intermediate-1-risk MDS, including chronic myelomonocytic leukemia (CMML)-1
De novo myelodysplastic syndromes (MDS): International Prognostic Scoring System intermediate-1 (IPSS-1) with poor risk cytogenetics or higher IPSS
MDS with at least one of the following poor-risk features:\r\n* Poor-risk cytogenetics\r\n* International Prognostic Scoring System (IPSS) score of intermediate-2 (INT-2) or greater\r\n* Treatment-related or secondary MDS\r\n* MDS diagnosed before age 21 years\r\n* Progression on or lack of response to standard deoxyribonucleic acid (DNA)-methyltransferase inhibitor therapy\r\n* Life-threatening cytopenias, including those requiring frequent transfusions
Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) intermediate-2 or higher; or therapy-related MDS
Patients with MDS (IPSS score ? 1.5)
Patients must have disease that requires therapy, including intermediate-1, intermediate-2, or high-risk disease according to the International Prognostic Scoring System (IPSS) or Dynamic-IPSS
Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia (CMML) with at least one of the following poor?risk features:\r\n* Poor?risk cytogenetics\r\n* International Prognostic Scoring System (IPSS) score of intermediate (INT)?2 of greater\r\n* Treatment?related or secondary MDS\r\n* MDS diagnosed before age 21\r\n* Progression on or lack of response to standard deoxyribonucleic acid (DNA)?methyltransferase inhibitor therapy\r\n* Life?threatening cytopenias, including those requiring frequent transfusions
Revised international prognostic scoring system (IPSS-R) intermediate, high or very high
Patients with myelodysplastic syndrome (MDS) with intermediate-2 or high risk per International Prognostic Scoring System (IPSS) (or intermediate, high, very high risk by Revised International Prognostic Scoring System [IPSS-R]) or myeloproliferative neoplasm; primary or secondary if high-risk features or refractory disease
MDS – low/intermediate-1 International Prognostic Scoring System (IPSS) risk category patients are eligible only if they have failed prior therapy or are transfusion-dependent
Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one transfusion per month), or intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk group
Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher IPSS-R risk group
Revised International Prognostic Scoring System (IPSS-R) criteria for intermediate, high-risk or very high-risk
Men or women, 18 years of age or older, with a confirmed diagnosis of international prognostic scoring system (IPSS) intermediate-1, intermediate-2 or high-risk MDS including Chronic Myelomonocytic Leukemia (CMML) or AML.