DIPSS Intermediate-1, Intermediate -2, or High risk (Passamonti et al 2010)
Participants must have pathologically confirmed primary myelofibrosis according to World Health Organization (WHO) criteria or secondary myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria\r\n* Intermediate-2/ high-risk disease as per Dynamic International Prognostic Scoring System (IPSS) (DIPSS) criteria OR\r\n* Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely\r\n** Red cell transfusion dependency\r\n** Unfavorable Karyotype\r\n** Platelet count =< 100 x 10^9/L
Diagnosis of primary or secondary myelofibrosis with transplant indication by Dynamic International Prognostic Scoring System (DIPSS)-plus (> intermediate -1)
Confirmed diagnosis of primary myelofibrosis or post-polycythemia vera / essential thrombocythemia myelofibrosis classified as high risk, intermediate-2 risk, or intermediate 1 risk by International Prognostic Scoring System (IPSS)
Intermediate (>3-4.5 points): a patient determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
Diagnosis of primary of secondary myelofibrosis with transplant indication by Dynamic International Prognostic Scoring System (DIPSS)-plus (> intermediate-1)
If the diagnosis is MF-CP, must have Dynamic International Prognostic Scoring System (DIPSS) intermediate-2/high risk disease and either be intolerant/resistant to ruxolitinib as determined by the treating investigator or ineligible for ruxolitinib therapy as determined by the treating investigator
Primary or secondary myelofibrosis intermediate or high risk by Dynamic International Prognostic Scoring System (DIPSS) in chronic or accelerated phase
Myelofibrosis with Dynamic International Prognostic Scoring System (DIPSS) scores of INT-2 or high risk or any risk category if life threatening cytopenias are present
For cohort 1: early stage MF (low or intermediate 1 stage as defined by Dynamic International Prognostic Scoring System [DIPSS]) without currently available treatment options
For cohort 2: intermediate-2 or high risk MF patients as defined by DIPSS either not eligible for ruxolitinib or having failed under ruxolitinib
For cohort 1 only: patients with evidence of intermediate 2 or high risk disease (according to DIPSS)
Recipients with myelofibrosis must have at least 2 of the following features, or be Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high risk:\r\n* Hemoglobin < 10 g/dl, or > 10 g/dl with transfusion dependence\r\n* WBC < 4,000 or > 30,000/mm^3 or requires cytoreductive therapy to maintain WBC < 30,000/mm^3\r\n* Abnormal cytogenetics
PART 1: Disease criteria\r\n* Diagnosis of primary MF (PMF) as defined by the 2008 World Health Organization classification system or diagnosis of secondary MF as defined by the International Working Group (IWG) for Myeloproliferative Neoplasms Research and Treatment criteria\r\n* Patients meeting the criteria for intermediate-1, intermediate-2 or high-risk disease by the Dynamic International Prognostic Scoring System (DIPSS) or DIPSS-plus scoring system
Myelofibrosis (MF):\r\n* Intermediate-2 or high risk by Dynamic International Prognostic Scoring System (DIPSS)-plus OR\r\n* Monosomal karyotype OR\r\n* Presence of inv(3)/i(17q) abnormalities OR \r\n* Other unfavorable karyotype OR leukocytes >= 40 x 10^9/L AND\r\n* Circulating blasts =< 9%
Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate-1, intermediate -2 or high risk disease according to the International Working Group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is >= 5 cm below left costal margin by physical exam
Patients with a diagnosis of primary myelofibrosis (PM), post polycythemia vera myelofibrosis (PPV MF), or post essential thrombocythemia myelofibrosis (PET MF) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to International Working Group (IWG-MRT) criteria
Myeloproliferative neoplasms/myelofibrosis, either primary as a result of polycythemia vera or essential thrombocythemia, with disease risk of intermediate or high-risk according to Dynamic International Prognostic Scoring System (DIPSS) criteria; blasts must be < 10% by bone marrow aspirate morphology
Patients must have histologically documented myelofibrosis (MF)\r\n* Patients with Dynamic International Prognostic Scoring System (DIPSS) plus intermediate stage 2 or higher risk MF; OR\r\n* Subset of intermediate stage 1 patients; defined by:\r\n** Poor-risk molecular profile (triple negative: JAK2, CALR, MPL); OR\r\n** Presence of any of the following mutations: ASXL1, SRSF2, EZH2, IDH1/2; OR\r\n** Severe thrombocytopenia, severe anemia, high peripheral blood blasts percentage; OR\r\n** Unfavorable cytogenetic abnormalities (rearrangements of chromosome 5 or 7 or >= 3 abnormalities
Intermediate-2/ high-risk disease as per Dynamic International Prognostic Scoring System (IPSS) (DIPSS) criteria OR intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely\r\n* Red cell transfusion dependency\r\n* Unfavorable karyotype\r\n* Platelet count < 100 x 10^9/l
DIPSS intermediate-2 or high risk MF
Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
Intermediate (>3 to 4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
Diagnosis of myelofibrosis (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 Working Group (IWG) criteria
High risk OR intermediate-2 risk as defined by Dynamic International Prognostic Scoring System (DIPSS), OR intermediate-1 risk as defined by DIPSS and associated with symptomatic splenomegaly, and/or hepatomegaly
High-risk or Intermediate-2 risk MF (as defined by the Dynamic International Prognostic Scoring System [DIPSS-plus])
Require treatment for MF and classified at least as intermediate risk level 1 defined by the International Working Group.
Patients must have Low or Intermediate 1 stage of disease as defined by International Working Group (IWG) risk stratification of primary myelofibrosis in the dynamic international prognostic scoring system (DIPSS). In addition, they must show some active hematopoiesis with a cellularity of at least 15%, irrespective of the degree of reticulin and/or collagen fibrosis as defined by Manoharan criteria.
Patients with Intermediate 2 or High risk stage of disease as defined by International Working Group (IWG) risk stratification of primary myelofibrosis in the dynamic international prognostic scoring system (DIPSS) and/or bone marrow biopsy showing less than 15% cellularity in the presence +2 or more reticulin fibrosis (by Manoharan criteria), collagen fibrosis, or osteosclerosis.
High risk OR intermediate-2 risk defined by dynamic international prognostic scoring system (DIPSS) OR intermediate-1 risk defined by DIPSS and associated with symptomatic splenomegaly and/or hepatomegaly
Intermediate-2/ high-risk disease as per Dynamic International Prognostic Scoring System (IPSS) (DIPSS) criteria or intermediate-1 risk disease with one of the following features within one year from screening:\r\n* Red cell transfusion dependency\r\n* Unfavorable karyotype \r\n* Platelet count < 100 x 10^9/L\r\n* Symptomatic splenomegaly\r\n* Peripheral blood (PB) blasts > 1%
Individuals with PMF, post-PV MF, or post-ET MF classified as high risk or intermediate risk as defined by the Dynamic International Prognostic Scoring System (DIPSS) for PMF or DIPSS Plus, if cytogenetics are available
Part II: Patients with one of the following documented conditions: CML in CP that is Philadelphia chromosome (Ph)-positive (by cytogenetics) or BCR-ABL1-positive by fluorescent in situ hybridization [FISH], or PCR), as well as resistant to at least 2 FDA-approved tyrosine kinase inhibitors (TKIs); or a myeloproliferative neoplasia which includes: PMF and myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) myelofibrosis (MF) (with intermediate-1, intermediate-2 or high risk disease according to the International Working Group [IWG] prognostic scoring system) (i.e., Non-Acute Group patients).
3. A pathologically confirmed diagnosis of AML or CMML-2 by World Health Organization (WHO) classification that is relapsed or refractory or for which no current therapies are anticipated to result in a durable remission, or MDS by WHO classification are RAEB-1 or RAEB-2 and that have failed at least three cycles of hypomethylating therapy, or primary (PMF), post-polycythemia vera (PPMF) or post-essential thrombocythemia (PTMF) MF by WHO classification, are high-risk category by the Dynamic International Prognostic Scoring System (DIPSS Plus), have ?1% circulating blasts, and have failed treatment with ruxolitinib
Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)\r\n* Intermediate-2 or high risk score by Dynamic International Prognostic Scoring System (DIPSS) Plus is required for a diagnosis of myelofibrosis
Primary or secondary myelofibrosis intermediate or high risk by Dynamic International Prognostic Scoring System 26 (DIPSS26) in chronic or accelerated phase
Any disease risk classification, as assessed by the Dynamic International Prognostic Scoring System (dIPSS)
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.
Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:
Patients must be high risk by belonging to one of the following risk groups:\r\n* Completion of adjuvant chemotherapy and pathologically negative lymph nodes, and a tumor measuring >= 2 cm in greatest diameter, and an Oncotype DX recurrence score > 25 (completed as standard of care) or a MammaPrint assay (completed as standard of care) in the high-risk category; patients with micrometastases as the only nodal involvement (pN1mi) are eligible, and will be categorized as node-negative \r\n* Completion of adjuvant chemotherapy, and pathologically 1-3 positive lymph nodes, and either an Oncotype DX recurrence score > 25, MammaPrint assay in the high-risk category (completed as standard of care), or tumor tissue with pathological grade III following local practice; if Oncotype DX is done, then RS must be > 25, similarly if the MammaPrint assay is performed it has to be high-risk; if the test is not done, but the patient has grade III disease then the patient is eligible and Oncotype DX or MammaPrint does not need to be performed\r\n* Completion of adjuvant chemotherapy and pathologically 4 or more positive lymph nodes\r\n* Completion of neoadjuvant chemotherapy and 1 or more positive nodes pathologically determined after chemotherapy\r\n* NOTE: patients who receive both the neoadjuvant and adjuvant chemotherapy may be registered in the neoadjuvant therapy risk group, provided they meet all the criteria above for that risk group\r\n* NOTE: in the lymph node positive groups, at least one metastasis >= 2.0 mm must be present; patients with micrometastases as the only nodal involvement (pN1mi) are eligible and will be categorized as node-negative
Patients will be excluded from this study if they are found to harbor “favorable” risk cytogenetics
Participants' disease must be defined as either high-risk or intermediate risk:\r\n* Definition of high-risk: any of the following high-risk features:\r\n** Positive margins (defined as tumor at ink)\r\n** Extracapsular extension of lymph node\r\n** Gross T4a or T4b primary tumor\r\n** Any lymph node >= 6 cm (N3)\r\n* Definition of intermediate-risk: absence of any high-risk features AND any one of the following intermediate risk features:\r\n** Close margins (defined as < 5 mm)\r\n** T3 or microscopic T4 tumor\r\n** Two or more positive lymph nodes involved with squamous cell carcinoma\r\n** Single lymph node > 3 cm and < 6 cm\r\n** Perineural invasion\r\n** Lymphovascular invasion\r\n** Level IV or level V involvement of oral cavity or oropharyngeal tumors\r\n** T2 oral cavity tumor with > 5 mm depth of invasion
Dose Expansion Cohort #4 - Patients will have relapse of CD123+ \other\ hematologic malignancies not included in the cohorts above (e.g., high-risk/very high-risk MDS, MPN, CMML, CML blast crisis). Other CD123+ malignancies may be considered upon discussion with the Medical Monitor.
Rapidly progressive or highly proliferative disease (total white blood cell count of >15 × 10^9/L) or other criteria that render the subject at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months.
Patients must have high risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
Presence of at least one of the features defining high risk; these include:\r\n* High risk chromosomal translocations by fluorescence in situ hybridization (FISH): t(4;14), t(14;16), t(14;20), deletion (del)(17p), del(1p), amplification 1q\r\n* Myeloma Prognostic Risk Signature (MyPRS) gene expression profiling (GEP)-70 high risk signature either from diagnosis or at time of registration for the study\r\n* Lactate dehydrogenase (LDH) > 300 U/L at diagnosis\r\n* Relapse from prior therapy within 12 months
Inclusion Criteria include:\n\n          -  Localized prostate cancer meeting the NCCN criteria of Intermediate Risk or patients\n             having only one NCCN high-risk feature\n\n               -  NCCN Intermediate Risk is defined as having at least one of the following: PSA\n                  10-20 ng/ml, Gleason score =7, T2b-T2c\n\n               -  High Risk with a single high risk feature is defined as having only one of the\n                  following: PSA>20 ng/ml, Gleason score 8-10, or T3a\n\n               -  Excluded are those in the following risk groups: Low risk; High risk with more\n                  than 1 high risk factor; Locally advanced/very high risk=T3b-T4; Metastatic: N1\n                  or M1\n\n          -  Planning to undergo standard prostate-only external beam radiation therapy\n\n          -  ECOG Performance Status 0-2\n\n        Exclusion Criteria include:\n\n          -  Liver disease, including known cirrhosis or active hepatitis\n\n          -  Patients on systemic corticosteroids (>10mg prednisone per day) or other\n             immunosuppressive drugs\n\n          -  Known HIV+ patients\n\n          -  Regional lymph node involvement or distant metastases\n\n          -  Patients planning to receive whole pelvic irradiation\n\n          -  Prior treatment for prostate cancer, except TURP or ADT. For ADT, it may only be given\n             for a maximum of 6 months\n\n          -  Patients who had or plan to have orchiectomy as the form of hormonal ablation\n\n          -  Known sensitivity or allergic reactions to acyclovir or valacyclovir
the newly diagnosed and/or previously unresected disease is judged to be at high risk for recurrence due to its size (>5 centimeters) or location at an anatomic site making it unlikely to be resected with negative margins (eg. adjacent to neurovascular structures)
High risk of systemic progression defined as:
Subject has poor-risk disease defined as International Prognostic Index (IPI) score ? 3 (high-intermediate or high-risk classification).
Understand that CC-122 could have a potential teratogenic risk.
Must meet criteria for high-risk MGUS or low-risk smoldering myeloma as described below:
Patients enrolling after only 1 failed induction attempt must meet at least one of the following additional eligibility criteria of high risk: ? 60 years of age adverse cytogenetics or molecular characteristics
Patients with significant edema leading to risk of brain herniation
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
Patients with high risk multiple myeloma in partial response (PR) or better at the time of enrollment with no prior progression and within 18 months from initiation of systemic anti-myeloma therapy, which may include single or planned tandem autologous HSCT. [High risk is defined by the presence of any one of the following: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1(1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high risk criteria based on commercially available gene expression profiling (GEP) ; and elevated beta-2 microglobulin (? 5.5 mg/L at diagnosis), detected at any time prior to enrollment]; or
Must meet criteria for high risk disease\r\n* Patients with INSS stage 3 disease are eligible with the following\r\n** MYCN amplification, regardless of age or additional biologic features\r\n** Age >18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
Must meet criteria for high risk disease\r\n* Patients with INSS stage 2a/2b with MYCN amplification regardless of age or additional biologic features
Primary resistant/refractory disease detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocols.
Relapsed multiple myeloma in patients that have been treated previously with autologous hematopoietic stem cell transplantation (auto-HCT), bortezomib and an imunomodulatory agent, AND with at least one of the following high-risk criteria \r\n* High-risk multiple myeloma defined by cytogenetic or fluorescence in situ hybridization (FISH) detection of any one or more of the following: \r\n** Deletion 17p \r\n** Translocation t(4;14) \r\n** Translocation t(14;16) \r\n** Translocation t(14;20)\r\n** Chromosome 1q gain \r\n** Chromosome 1p deletion\r\n** Deletion 13q by conventional karyotyping (FISH only not acceptable)\r\n** Hypodiploidy\r\n* High-risk gene expression profiling (GEP) at the time of relapse (by Signal Genetics Myeloma Prognostic Risk Signature [MyPRS] score)\r\n* Beta-2 (B2) microglobulin > 5.5 mg\r\n* Plasmablastic morphology (> 2%)\r\n* Relapsed plasma cell leukemia
NHL (Part 1 and 2): Intermediate or high risk by Ann Arbor Staging with Cotswald Modifications that meets criteria for active disease requiring therapy.
PROCUREMENT INCLUSION CRITERIA: Any patient regardless of sex with a solid tumor expressing any of the following antigens (PRAME, SSX2, MAGEA4, NY-ESO1-1 and/or survivin) with:\r\n* Active disease after first line therapy;\r\n* Refractory disease;\r\n* As adjuvant therapy for high risk disease (high risk disease is a disease that has a > 50% risk of progression within 5 years)
Any patient regardless of sex with a solid tumor expressing any of the following antigens (PRAME, SSX2, MAGEA4, NY-ESO1-1 and/or survivin) with:\r\n* Active disease after first line therapy;\r\n* Refractory disease;\r\n* As adjuvant therapy for high risk disease (high risk disease is disease that has a > 50% risk of progression within 5 years)
AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2)
Non-surgical candidates due to:\r\n* Desire for fertility preserving treatment\r\n* Unacceptable surgical risk as defined by: \r\n** American Society of Anesthesiologists physical status (ASA) >= 4 and/or perioperative cardiac risk > 5% and/or perioperative respiratory failure risk > 5% AND\r\n** Independent medicine or cardiology pre-op consultation concluding ‘high’ surgical risk\r\n* Patient determined to be a non-surgical candidate by the primary treating physician
Must have low, intermediate-risk or high-risk disease, defined as:\r\n* Low-risk: Embryonal, botryoid, spindle cell tumors only\r\n** Subset 1\r\n*** Stage 1, Group I, Group II\r\n*** Stage 1 Group III orbital only\r\n*** Stage 2, Group I, Group II\t\r\n** Subset 2\r\n*** Stage 1, Group III non orbit\r\n*** Stage 3, Group I, II\r\n* Intermediate-risk: Embryonal, botryoid, or spindle cell rhabdomyosarcoma (RMS)\r\n** Stage 2 or 3 and Group III\r\n** Alveolar, undifferentiated, or anaplastic RMS\r\n** Stage 1-3, group I-III\r\n* High-risk: Embryonal, botryoid, spindle cell, alveolar, undifferentiated, or anaplastic RMS with metastatic disease at diagnosis (stage 4)\r\n* Patients treated on RMS13 in the low or intermediate risk arm that experience disease progression prior to week 13 will transfer to the high risk arm and proceed with high risk chemotherapy starting at week 1 of the protocol
High risk for poor compliance with therapy or follow-up as assessed by investigator
High risk T3 tumors that fulfill any of the following – circumferential tumor, extension into mesorectal fascia > 5 mm, prediction of positive circumferential resection margin, are also excluded.
Patients with one of the high risk myeloid diseases as outlined below. Patients must have less than 5% blasts on the last bone marrow (BM) evaluation prior to starting the conditioning regimen. Diseases included on this protocol include:\r\n* Acute myeloid leukemia (AML) in first complete remission (CR1) with intermediate or high risk features as defined below:\r\n** Cytogenetic abnormalities which are not considered “good risk” cytogenetic features (i.e t(8:21), t(15:17), inv 16 without c-kit mutations. And/or\r\n** Therapy related AML with history of antineoplastic therapy (radiation and/or chemotherapy) And/or\r\n** Normal karyotype with mutations of FLT3, RUNX1, TP53 mutation, ASXL1 or any others that are considered to be high risk\r\n* AML in >= 2nd remission\r\n* Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/myeloproliferative neoplasms (MPN) overlap syndrome with:\r\n** International prognostic scoring system risk score intermediate-2 (INT-2) or high risk at the time of transplant evaluation. And/or\r\n** Any risk category if life-threatening cytopenia exists And/or\r\n** Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.\r\n* Chronic myelomonocytic leukemia (CMML): CMML-1 or CMML-2.\r\n* Chronic myeloid leukemia (CML) with the following features:\r\n** Patients who have failed or are intolerant to BCR-ABL tyrosine kinase inhibitors. And/or\r\n** CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g T351l mutation)\r\n* Patients with severe aplastic anemia.
Has a target lesion/s in a region that previously received high dose radiation therapy (RT) (>50 Gy) demonstrating any of the following: \r\n* carotid artery encasement (> 180 degrees) \r\n* unprotected carotid artery (i.e. skin is directly over the carotid without intervening soft tissue, especially after prior neck dissection without a vascularized free flap) (a&b due to risk of carotid blow out)\r\n* skin infiltration by tumor (due to risk of fistula)\r\n* located in the larynx/hypopharynx primaries (due airway threat) treated with high dose radiation therapy (>50Gy) within 6 months or less of trial enrollment
Subject has a history of Type 1 Diabetes (T1D) or is considered at high risk for T1D, where high risk is defined as
Eligible patients with a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories:\r\n* Acute myelogenous leukemia:\r\n** Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myelogenous leukemia (AML) i.e., monosomal karyotype, -5, 5q-, -7, 7q-, 11q23-non t (9;11), inv (3), t (3;3), t (6;9), t (9;22) and complex karyotypes (>= 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease\r\n** Patients with active disease\r\n** Patients with chemosensitive active disease\r\n* Acute lymphocytic leukemia:\r\n** Patients with de novo or secondary disease according to NCCN guidelines for acute lymphocytic leukemia (ALL) hypoploidy (< 44 chromosomes); t (v;11q23): MLL rearranged; t (9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (>= 30,000 for B lineage or >= 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p\r\n** Patients with active disease\r\n** Patients with chemosensitive active disease\r\n* Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories
Patients with significant edema leading to risk of brain herniation
Patients at very high risk for relapse post HCT as defined by very high disease risk index.
Has intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
Patients with High-Risk Multiple Myeloma. High-risk is defined by the presence of any one of the following: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1(1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high-risk criteria based on commercially available gene expression profiling (GEP) detected at any time prior to enrollment;
High-risk neuroblastoma with either primary refractory or secondary refractory osteomedullary disease (persistent neuroblastoma at osteomedullary sites after prior treatment)
Poor psychiatric risk
Very high (>6 points).
High (>4.5-6 points).
High-Risk NMIBC as classified per the 2016 AUA Guidelines
Evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months and/or poses a significant suicide risk in the judgment of the investigator
Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk
Patients with any high-risk features will also be eligible, including those who:\r\n* Fail to achieve complete remission with initial combination chemotherapy\r\n* Have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass >= 5 cm or other residual mass >= 10 cm accompanied by other features of persisting disease (e.g., positron emission tomography [PET] scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy
One of the two following populations:\r\n* High risk for recurrence of RCC after nephrectomy, in the opinion of the investigator, OR\r\n* Locally advanced, unresectable or metastatic disease, in the opinion of the investigator, and good or intermediate risk by Clinical Trial Independent Data Monitoring Committee (IDMC) Heng Criteria
Patients with favorable, intermediate and poor risk categories will be eligible for the study; patients must be categorized according to favorable versus intermediate/poor risk status at registration; international Metastatic RCC Database Consortium (IMDC) must be used to determine prognostic factors
Patients must have undergone resection of the disease and demonstrate high risk pathologic features including:\r\n* T4\r\n* Node positive disease\r\n* T2/T3N0 disease with any 1 additional feature, including:\r\n** Recurrent Disease\r\n** Perineural invasion\r\n** Lymphovascular space invasion\r\n** Poorly differentiated histology\r\n** Positive Margins\r\n** Satellitosis or in-transit metastases\r\nNote: Not all patients with T2N0 cancer with one additional risk factor may be ideal candidates for this study, such as patients with only focal perineural invasion without other adverse features; clinical judgment should be used by the investigator in carefully selecting patients believed to be at significant risk of recurrence with radiation alone
This treatment is for patients with high risk hematologic malignancies; high risk is defined as:\r\n* Any patient with a hematologic malignancy in which allogeneic HSCT is pursued with the expectation of cure; patients may have post-treatment residual disease, but the disease should be stable or minimally progressive and must be responsive to chemotherapy\r\n* Any patient with an untreated hematologic malignancy in which allogeneic HSCT is thought to be the sole or the best option for cure and in which prior treatment is unlikely to meaningfully address the disease\r\n* Patients without morphologic evidence of disease but with high risk features which would predict for relapsed despite remission at HSCT such as adverse cytogenetics, third (3rd) or greater complete response (CR), or failure to recover peripheral blood counts to normal ranges; while these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement
Participation in a different trial that increases a patient’s risk of VTE
Treatment plan to receive a continuous course of IMRT delivered as single daily fractions of 2.0 to 2.1 Gy with a cumulative radiation dose between 60 Gy and 70 Gy depending on whether patients are considered post-operative high risk or unresectable/organ preservation high risk. Planned radiation treatment fields must include at least two oral sites buccal mucosa, retromolar trigone, floor of mouth, oral tongue, soft palate, hard palate) with a portion of each site receiving a minimum total of 50 Gy.
Male or female subjects, age 18 to 75 years admitted to hospital with a clinical diagnosis of acute PE categorized as low risk or intermediate-risk or submassive PE and for whom catheter-based therapy is not planned;
Myelodysplastic syndrome, myeloproliferative neoplasms, or myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) overlap syndrome with:\r\n* International prognostic scoring system risk score of intermediate (INT)-2 or high risk at the time of transplant evaluation\r\n* Any risk category if life-threatening cytopenia exists\r\n* Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype
Have at least 2 of the following high risk features associated with her DCIS-high grade (grade II-III), palpable mass, hormone receptor negative (less than 1%), Her2 positive, young age (less than 45 years old), and large size (greater than 5 cm)
No risk of vital organ compression.
Patients deemed to be “high risk” by pre admission testing (care process model [CPM]) or by a preoperative risk assessment by the hospitalist for perioperative complications
Subjects must have a confirmed diagnosis of active multiple myeloma according to IMWG criteria; in addition, subjects must have “high-risk” multiple myeloma according to one of the following criteria:\r\n* Any of the following high-risk cytogenetic features, documented by fluorescence in situ hybridization (FISH) or metaphase karyotyping: deletion 17p, t(4;14), t(14;16), t(14;20)\r\n* Standard-risk cytogenetics but elevated lactate dehydrogenase (LDH) and beta-2-microglobulin > 5.5 mg/L (i.e., Revised International Staging System [R-ISS] stage III)
PART 2 GROUP 1 INCLUSION CRITERIA: Subject has high-risk neuroblastoma with a protocol-defined genomic aberration that allows assignment to Group 1
PART 2 GROUP 2A INCLUSION CRITERIA: Subject has high-risk neuroblastoma with a protocol-defined genomic aberration that allows assignment to Group 2
PART 2 GROUP 3 INCLUSION CRITERIA: Subject has high-risk neuroblastoma with a protocol-defined genomic aberration that allows assignment to Group 3
Patients must have high risk or intermediate risk disease, defined below; staging evaluation should be determined by imaging studies and complete head and neck exam in accordance with the American Joint Committee on Cancer Staging Manual, 7th edition\r\n* High risk patient must meet one of the following criteria:\r\n** Surgically unresectable oral cavity; patients who are technically resectable but refuse surgery due to morbidity (eg. total glossectomy) are also eligible; medically inoperable patients are not eligible\r\n** Larynx: T4 any N; T2-3 and >= N2a\r\n** Hypopharynx: T1-2N1-3 or T3-4N0-3\r\n** Oropharynx: p16(-) AND T3-4 or >= N2a\r\n** Unknown primary: p16(-) AND >= N2a\r\n* Intermediate risk patients must meet one of the following criteria:\r\n** Oropharynx: p16(+) AND one of the following\r\n*** T3 or >= N2a AND >= 10 pack-years tobacco exposure \r\n*** T4 or N3 disease irrespective of tobacco exposure\r\n** Unknown primary: p16(+) AND one of the following:\r\n*** >= N2a AND >= 10 pack-years tobacco exposure\r\n*** N3 disease irrespective of tobacco exposure\r\nNote: for patients with oropharyngeal or unknown primary tumors, p16 status must be known, and can be performed at the local site; p16-positive disease is defined as >= 70% of tumor cells demonstrating diffuse nuclear and cytoplasmic staining by p16 immunohistochemistry (IHC); a positive test for human papilloma virus (HPV) -16 by in-situ hybridization (ISH), if this is the local site preference for assessing HPV status, may substitute for p16 IHC testing; p16 staining is not required for non-oropharyngeal sites
Has previously untreated, de novo, non-M3 acute myeloid leukemia (AML) with intermediate-risk disease (intermediate-I or intermediate-II) as defined by ELN criteria OR normal cytogenetics (after analysis of 20 or more metaphases) with mutated nucleophosmin (NPM1) without FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD); monoallelic CEBPA mutations are not considered favorable risk and are therefore eligible
understand that the study medication may have teratogenic risk
DONOR: A comorbid condition which, in the view of the investigators, renders the subject at high risk from treatment complications
Patients must be at high risk for recurrence, which will be defined during the pre-treatment screening period as meeting one of the following criteria:\r\n* A histologically positive nodal deposit >= 0.2 mm\r\n* Histologic grade 3\r\n* Peritumoral lymphatic vessel or vascular invasion\r\n* Oncotype Dx score of 25 or greater
Patient has very low risk, low risk, intermediate risk or very high risk disease as defined by the NCCN
Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition that investigators suspect may prohibit use of the investigational product, affect interpretation of study results, or put the patient at high risk.
High risk for relapse defined as: 1st CR with high risk features for relapse (including history of prior malignancy treated with chemotherapy or radiotherapy, or history of myelodysplastic syndrome, myeloproliferative disorder, chronic myelomonocytic leukemia, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN] or other hematologic malignancy thought to have evolved to AML [i.e., secondary AML, (sAML)]; high risk cytogenetics at diagnosis; fms-related tyrosine kinase 3 [FLT3] mutated at diagnosis; or presence or minimal residual disease assessed by polymerase chain reaction [PCR], cytogenetics, and/or flow cytometry at time of enrollment) 2nd CR regardless of disease characteristics at the time of diagnosis
High-risk pathologic features must be present: compromised/positive surgical margins (=< 2 mm) or extra-nodal extension (patient with other high-risk features gross perinueral invasion, bone invasion, angiolyphatic invasion, or a constellation of these factors may be eligible based on case-by-case basis at discretion of principal investigator)
A co-morbid condition that, in the Investigator's opinion, renders the subject at high risk for treatment complications.
It is not required that patients have the risk factors mentioned
Patients who due to age, pre-existing medical conditions, or, prior therapy are considered to be at high-risk for regimen-related toxicity associated with fully ablative transplant conditioning, and therefore reduced intensity conditioning is recommended
Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL), refractory to or relapsed after at least one prior standard therapy or untreated with deletion (del)(17p) by fluorescence in-situ hybridization (FISH) (high-risk cytogenetics) and have an indication for treatment by IWCLL 2008 criteria (Cohort 1) OR have been on ibrutinib for at least 9 months with measurable persistent disease (absolute lymphocyte count [ALC] > 4 K/muL, any lymph node > 1.5 cm by computed tomography [CT] scan, or > 30% lymphocytes on bone marrow aspirate differential) (Cohort 2), OR patients will have a diagnosis of RT, refractory to and/or relapsed after at least one prior standard therapy or untreated with del(17p) by FISH (high-risk cytogenetics) (Cohort 3)
Patients must have relapsed or refractory acute leukemias or high-risk MDS for which no standard therapies are anticipated to result in a durable remission
Inability to hold anticoagulation for surgery due to high risk of a cerebral vascular event, myocardial event, or like risk
Myeloid disorder (myelodysplastic syndrome [MDS] with intermediate/high risk features or refractory disease or myeloproliferative disorder; primary or secondary if high-risk features or refractory disease)
Patients must have high-risk neuroblastoma with at least ONE of the following:
Primary resistant/refractory disease detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include Children's Oncology Group trials: A3973, ANBL0532, ANBL09P1, etc.).
High-risk NB, as defined by risk-related treatment guidelines and the International NB Staging System, i.e., stage 4 with (any age) or without (> 18 months) v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN)-amplification, or MYCN-amplified NB other than stage I
High risk for distal recurrence defined as any of the following conditions: A) Confirmed both monosomy 3 and 8q amplification; B) Class II tumor
Prior kyphoplasty, vertebroplasty, local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture) are permitted
Patients who have had chemotherapy for MM; exception: local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture)
Significant risk of suicide based on the investigator’s judgment
Patients with high risk multiple myeloma who are transplant candidates, in partial response (PR) or better; high risk will be defined as patients with any of the following:\r\n* Fluorescence in situ hybridization showing t(4:14), t(14:16)t (14:20) deletion (Del) 17/17p or gain (amp) 1q; \r\n* Deletion 13 by conventional cytogenetic analysis; \r\n* High risk signatures as determined by the GEP-70 or EMC-92 gene expression profiles;\r\n* Relapsed disease within 18 months of prior autologous stem cell transplant (ASCT)
All other patients, including those with treatment related malignancies and/or those who have AML derived from MDS, will have received extensive prior chemo/radiotherapy and, therefore, will be considered to be at poor risk of conditioning and transplant related morbidities, and potentially transplant related mortality; patients with life threatening non-malignant genetic and acquired disorders will also, by virtue of their history of, optional transfusions and/or infection be considered poor risk; stopping rules for non-relapse related mortality in these heavily treated patients are, therefore, slightly less stringent than patients in the poor risk transplant groups; stopping rules for the principal endpoints of graft failure and GvHD are the same for all groups
Acute myelogenous leukemia in high risk CR1 as defined by at least one of the following: \r\n* Greater than 1 cycle of induction therapy required to achieve remission\r\n* Preceding myelodysplastic syndrome (MDS)\r\n* Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities\r\n* French-American-British (FAB) M6 or M7 leukemia, or\r\n* Adverse cytogenetics for overall survival such as: \r\n** Those associated with MDS\r\n** Complex karyotype (>= 3 abnormalities); or \r\n** Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)]\r\n* Other risk factors determined by the patient’s attending physician to be high risk features requiring transplantation
High-risk MDS status-post cytotoxic chemotherapy
Patients with seminomatous or nonseminomatous germ-cell tumors (GCT) in one of the following groups: A) first relapse or progression or second response with an intermediate or high risk according to the Beyer model; B) second relapse or beyond
Acute myelogenous leukemia (AML) at the following stages:\r\n* High risk first complete remission (CR1), defined as:\r\n** Having preceding myelodysplasia (MDS)\r\n** High risk cytogenetics (high-risk cytogenetics: del (5q) –5, -7, abn (3q), t (6;9) complex karyotype (>= 5 abnormalities) with any minimal residual disease (MRD) status\r\n** Requiring >= 2 cycles chemotherapy to obtain complete response (CR)\r\n** High allelic ratio fms-related tyrosine kinase 3 (FLT3)/internal tandem duplications positive (ITD+)\r\n** Standard risk cytogenetics with positive MRD at end of induction \r\n* Second or greater CR\r\n* First relapse with < 25% blasts in bone marrow
Low-risk disease, defined as all MLL germline cases
Medium-risk disease, defined by 1 of the following criteria:
High-risk disease, defined by MLL rearrangement AND meets the following criteria:
Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
Patients must have histologically documented multiple myeloma (MM)\r\n* Patients in early relapse (less than 24 months from initiation of systemic anti-myeloma therapy which may include single or planned tandem autologous transplant) after primary therapy that included and autologous HSCT; OR\r\n* Later stage; OR\r\n* High risk factors defined by the presence of any one of the following detected at any time prior to enrollment: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1 (1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high risk criteria based on commercially available gene expression profiling; OR\r\n* Extramedullary disease, plasma cell leukemia or high lactate dehydrogenase (LDH)
Patient has pathologic high risk factors on either the initial biopsy specimen report or follow up biopsy (if done): high histologic grade, mucinous histology, lymphatic or vascular invasion.
High or intermediate-2 risk disease, as defined per protocol
Histological evidence of oral intra-epithelial neoplasia within 12 months prior to enrollment; subjects with a history or clinical diagnosis suggestive of oral intra-epithelial neoplasia, or patients with a history of invasive oral cancer are eligible, but must have a confirmed histological diagnosis of oral intra-epithelial neoplasia before randomization; histological evidence of oral intraepithelial neoplasia on an invasive oral cancer resection specimen is acceptable; a visible, measurable, clinical lesion (such as leukoplakia and/or erythroplakia) is not required; only individuals with high risk profiles will be considered eligible for randomization; high risk profiles are defined as patients without a prior oral cancer and have loss of heterozygosity (LOH) at 3p14 and/or 9p21 plus at least at one additional chromosomal site (4q,8p,11p,13q, or 17p) or patients with a prior oral cancer history and have LOH at 3p14 and/or 9p21; all high risk patients must also meet the additional eligibility criteria
AML and ALL in 1st complete remission (CR) at high risk of relapse based on negative prognostic factors (for the definition of high-risk of relapse see Appendix H).
Low-intermediate risk of relapse defined as:
Confirmed high-risk HPV infection by a commercially available high-risk DNA assay (eg, Hybrid Capture II [Qiagen]);
Patients must have high risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
Intermediate risk based on National Comprehensive Cancer Network (NCCN)
High risk AML (see NCCN risk criteria)
Low risk AML (see NCCN risk criteria)
Patients must have stage 3 high-risk neuroblastoma or metastatic neuroblastoma (not 4S)
All patients will undergo testing for prognostic factors according to the CLL-IPI (testing obtained ? 120 days prior to registration)\r\n* Note: Patients with CLL-IPI risk category of high risk or very high risk (total score of 4-10) will be randomized to Arms A or B\r\n* Note: Patients with CLL-IPI risk category of low risk or intermediate risk (total score of 0-3) will be registered to Arm C
For high risk and very high risk CLL-IPI (Arms A and B) only; obtained ? 30 days prior to randomization: Absolute neutrophil count (ANC) ? 1500/mm^3
For high risk and very high risk CLL-IPI (Arms A and B) only; obtained ? 30 days prior to randomization: Platelet count ? 100,000/mm^3
For high risk and very high risk CLL-IPI (Arms A and B) only; obtained ? 30 days prior to randomization: Hemoglobin ? 11.0 g/dL
For high risk and very high risk CLL-IPI (Arms A and B) only; obtained ? 30 days prior to randomization: Aspartate aminotransferase (aspartate transaminase [AST]) ? 3 x upper limit of normal (ULN)
For high risk and very high risk CLL-IPI (Arms A and B) only; obtained ? 30 days prior to randomization: Creatinine ? 1.5 X ULN
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
For patients with oropharyngeal cancer only: the institution will do p16 testing, and if p16 is negative, this tissue must be submitted for central review for confirmation before Step 2 registration; note: if the institution finds that the patient is p16 positive, the patient is excluded from this trial on the basis of distinct biology, prognosis, and low- or intermediate-risk rather than high-risk status
Drugs which have an increased risk for QTc prolongation should be avoided
Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician
>= 55 years of age with AML of any risk classification, or 18-54 years of age with intermediate or high risk AML as defined by National Comprehensive Cancer Network (NCCN) risk assignment
High-risk acute myeloid leukemia in CR1 with any of the following features:\r\n* Complex karyotype (>= 3 clonal chromosomal abnormalities)\r\n* Any of the following high risk chromosomal abnormalities: \r\n** Monosomal karyotype (-5, 5q-, -7, 7q-)\r\n** t(11q23), t(9;11), inv(3), t(3;3) t(6;9) t(9;22)\r\n** Normal karyotype with FLT3-internal tandem duplication (ITD) mutation
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus
Any co-morbid condition that is in the view of the attending physician renders the patient at high risk from treatment complications
Patients must have high-risk neuroblastoma
HIGH RISK PATIENTS:
Patients must have adverse-risk AML defined as poor-risk karyotype (complex, monosomal or other known poor risk cytogenetic abnormality), poor-risk mutations/fusion genes or known history of antecedent hematologic disorder, or treatment related AML, or be >= 60 years of age
Patients must have high risk or intermediate risk disease, defined below; staging evaluation should be determined by imaging studies and complete head and neck exam in accordance with the American Joint committee on Cancer Staging Manual, 7th edition\r\n* High risk patients must meet one of the following criteria: \r\n** Unresectable oral cavity\r\n** Larynx: T4 any N; T2-3 and >= N2a\r\n** Hypopharynx and p16(-) oropharynx: stage III-IVb except T1N1\r\n** p16(-) Oropharnyx: stage III-IVb except T1N1\r\n* Intermediate risk, p16(+) oropharynx patients must meet one of the following criteria:\r\n** T3 or >= N2a AND >= 10 pack-years tobacco exposure \r\n** T4 disease, irrespective of smoking status\r\n** N3 disease, irrespective of smoking status\r\n*** Note: for oropharyngeal patients, p16 status must be known, and can be performed at the local site; p16-positive disease is defined as >= 70% of tumor cells demonstrating diffuse nuclear and cytoplasmic staining by p16 immunohistochemistry (IHC); a positive test for human papilloma virus (HPV)-16 by in-situ hybridization (ISH), if this is the local site preference for assessing HPV status, may substitute for p16 IHC testing; p16 staining is not required for non-oropharyngeal sites
High risk neuroblastoma with persistent or relapsed disease
Patients must have at least one of the following indicators of poor risk disease:\r\n* >= 3 risk factors by the Follicular Lymphoma International Prognostic Index, or 2 risk factors by the Follicular Lymphoma International Prognostic Index and at least one bulky mass or lymph node > 6 cm in size \r\n* Follicular Lymphoma International Prognostic Index (FLIPI score):\r\n** Age > 60 years\r\n** Involvement of > 4 nodal sites\r\n** Stage III-IV disease\r\n** Hemoglobin < 12.0 g/dL\r\n** Lactate dehydrogenase (LDH) > upper limit of normal (ULN)\r\n*** 0-1 of the above risk factors: low risk\r\n*** 2 risk factors: intermediate risk\r\n*** >= 3 risk factors: poor risk
Patients with pre-existing medical conditions or other factors that renders them at high risk for regimen related toxicity or ineligible for a conventional myeloablative HCT
Patients with any high-risk features will also be eligible, including those who:\r\n* Fail to achieve complete remission with initial combination chemotherapy\r\n* Patients with bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass >= 5 cm or other residual mass >= 10 cm accompanied by other features of persisting disease (e.g., Gallium or positron emission tomography (PET) scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible; if possible, persistent disease should be proven by biopsy
Patients must have high risk disease as defined below:\r\n* High risk PV ANY ONE of the following:\r\n** Age > 60 years\r\n** Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the myeloproliferative neoplasm [MPN]) either after diagnosis or within 10 years before diagnosis and considered to be disease related\r\n** Significant (i.e. > 5 cm below costal margin on palpation) or symptomatic (splenic infarcts or requiring analgesia)\r\n** Platelets > 1000 x 10^9/L\r\n** Diabetes or hypertension requiring pharmacological therapy for > 6 months\r\n* High risk ET ANY ONE of the following:\r\n** Age > 60 years\r\n** Platelet count > 1500 x 10^9/L\r\n** Previous documented thrombosis, erythromelalgia or migraine headaches (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related\r\n** Previous hemorrhage related to ET\r\n** Diabetes or hypertension requiring pharmacological therapy for > 6 months
Patients must have high risk disease as defined below:\r\n* High risk PV ANY ONE of the following:\r\n** Age >= 60 years\r\n** Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the myeloproliferative neoplasm [MPN]) either after diagnosis or within 10 years before diagnosis and considered to be disease related\r\n** Significant splenomegaly (> 5 cm below the left costal margin) or symptomatic splenomegaly (splenic infarcts or requiring analgesia)\r\n** Platelets > 1000 x 10^9/L\r\n** Diabetes or hypertension requiring pharmacological therapy for > 6 months\r\n* High risk ET ANY ONE of the following:\r\n** Age >= 60 years\r\n** Platelet count > 1500 x 10^9/L\r\n** Previous documented thrombosis, erythromelalgia or migraine headaches (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related\r\n** Previous hemorrhage related to ET\r\n** Diabetes or hypertension requiring pharmacological therapy for > 6 months
Patients must have recurrent/progressive high-risk neuroblastoma, refractory high-risk neuroblastoma that had less than a partial response to standard treatment or persistent high-risk neuroblastoma that had at least a partial response to standard treatment.
Poor medical risk
Must have ? 1 of the following high-risk prognostic factors:
Inclusion Criteria:\n\n        For Part 1:Patients must have one of the following diagnoses:\n\n          -  Aggressive systemic mastocytosis (ASM) as confirmed by World Heath Organization (WHO)\n             diagnostic criteria.\n\n          -  Systemic mastocytosis-associated hematologic non-mast cell disease (SM-AHNMD) as\n             confirmed by WHO diagnostic criteria, and the patient also has at least 1 C-finding\n             attributable to systemic mastocytosis (SM). The AHNMD must be myeloid, with the\n             following exceptions that are excluded: Acute myeloid leukemia (AML), Myelodysplastic\n             syndrome (MDS) that is very high- or high-risk as defined by the International\n             prognostic scoring system for myelodysplastic syndromes (IPSS-R) and Philadelphia\n             chromosome positive malignancies.\n\n          -  Mast cell leukemia (MCL) as confirmed per WHO diagnostic criteria.\n\n          -  Histologically- or cytologically- confirmed myeloid malignancy as confirmed by IWG-MRT\n             or WHO diagnostic criteria that is relapsed or refractory to standard treatments. AML,\n             MDS that is very high- or high-risk as defined by the IPSS-R, and Philadelphia\n             chromosome positive malignancies are excluded.\n\n          -  Upon discussion with the sponsor, other relapsed or refractory, potentially\n             avapritinib-responsive hematologic neoplasms (e.g., evidence of aberrant KIT or\n             platelet derived growth factor receptor (PDGFR) signaling) may be considered for\n             enrollment.\n\n        For Part 2:\n\n          -  Group 1: ASM as confirmed by WHO diagnostic criteria.\n\n          -  Group 2: SM-AHNMD as confirmed by WHO diagnostic criteria, that also has at least 1\n             C-finding attributable to SM. The AHNMD must be myeloid, with the following exceptions\n             that are excluded: AML, MDS that is very high- or high-risk as defined by the IPSS-R,\n             and Philadelphia chromosome positive malignancies.\n\n          -  Group 3: MCL as confirmed per WHO diagnostic criteria.\n\n        Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.\n\n        Exclusion Criteria:\n\n          -  QT interval corrected using Fridericia's formula (QTcF) >470 milliseconds\n\n          -  Platelet count <25,000/mL\n\n          -  Absolute neutrophil count <500/mL\n\n          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 x the upper\n             limit of normal (ULN); >5 × ULN if associated with clinically suspected liver\n             infiltration by mastocytosis or another disease for which the patient enrolled into\n             the study\n\n          -  Total bilirubin >1.5 × ULN; >3 × ULN if associated with liver infiltration by the\n             disease being treated or in the presence of Gilbert's Disease\n\n          -  Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min\n\n          -  Brain malignancy or metastases to the brain\n\n          -  History of a seizure disorder or requirement for anti-seizure medication\n\n          -  Known risk of intracranial bleeding, such as a brain aneurysm or history of subdural\n             or subarachnoid bleeding
Has previously untreated AML and is considered to be at high risk for disease progression and/or is unlikely to derive more than transient benefit from standard therapy by having at least one of the following:
Has previously untreated AML and is considered to be at high risk for disease progression and/or is unlikely to derive more than transient benefit from standard therapy by having at least one of the following:
Refrain from sperm and blood donation for at least 90 days after the final dose of durvalumab 8. For Cohort A subject must be transplant non-eligible (TNE) and meet at least one of the following high risk factors:
Have one of the following high risk factors at the time of NDMM diagnosis;
Patients aged < 50 yrs at high risk for regimen related toxicity using standard high dose regimens; factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart or previous failed HCT
Subject must have untreated, histologically proven high-risk DLBCL defined by IPI 3 to 5 and/or Double-hit or higher or double protein expression
patients must have high intermediate or high risk disease
For the Phase II portion only, patients must have high-risk MM based on one or more of the following criteria at the time of initial diagnosis (prior to any chemotherapy):\r\n* Poor-risk genomic signature according to the University of Arkansas 70-gene model (available clinically as myeloma prognostic risk score [MyPRS] score, Signal Genetics, Inc) AND/OR\r\n* Translocation (14;16), and/or translocation (14;20), and/or deletion (17p) by fluorescence in-situ hybridization (FISH) or cytogenetics AND/OR\r\n* Primary plasma cell leukemia (defined by either >= 2,000 plasma cells/mL of peripheral blood, or 20% on a manual differential count) AND/OR\r\n* Serum lactate dehydrogenase (LDH) >= 2 x institutional upper limit of normal (IULN) AND/OR\r\n* 1q21 amplification by FISH analysis AND/OR\r\n* High risk by the SKY92 signature\r\n* All tests for establishing high risk status must be completed within 28 days prior to registration for patients with no prior therapy, or within 28 days prior to initiation of first Induction course for patients with prior therapy
Only patients with Relapse Risk Score > 0 (“high risk”) will be enrolled during Part 1; patients with all Relapse Risk Scores will be enrolled during Part 2 (low risk group terminated August 2014)
Have uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain.
Very high (>6 points),
High (>4.5 to 6 points), or
Patients with any of the following risk factors:
current or prior high-risk sexual activity,
current or prior high-risk sexual activity,
Patients must be intermediate or high-risk Rai stage CLL\r\n* Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly\r\n* High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia
Patients with all three intermediate risk factors who also have >= 50% of the number of their biopsy cores positive for cancer are ineligible for this trial
High or high-intermediate disease risk.
At an increased risk of hemorrhage
Is participating in another medical device trial involving colectomy with anastomosis First 20 subjects ONLY: • Is diagnosed with high risk cancer as determined by preoperative clinical evidence or diagnostic imaging (if patient's cancer stage has been downstaged through treatment prior to baseline screening, subject is allowed to be included):
Subjects must have a target meningioma that is not amenable to surgery due to patient preference or high risk for surgical complications
Newly diagnosed and recurrent high grade gliomas (World Health Organization [WHO] grades III & IV) and high risk WHO grade II gliomas who are to begin treatment with monthly high dose temozolomide therapy
Patients must have histologically confirmed SMM based on the following criteria:\r\n* (A) Mayo clinic criteria (patient must have at least 2 risk factors present):\r\n** 1. Bone marrow core biopsy plasma cell involvement by cluster of differentiation (CD)138 immunohistochemistry >= 10%\r\n** 2. Monoclonal spike >= 3 g/dL\r\n** 3. Free light chain ratio in serum < 0.125 or > 8; *2 of 3 risk factors: intermediate risk for progression at a rate of 51% at 5 years, *3 of 3 risk factors: high risk for progression at a rate of 76% at 5 years\r\n* OR (B) Programa para el Tratamiento de Hemopatias Malignas (PETHEMA) criteria (patient must have at least 1 risk factor present)\r\n** 1. >= 95% abnormal plasma cells/total plasma cells in bone marrow compartment\r\n** 2. Immunoparesis *1 of 2 risk factors: intermediate risk for progression at a rate of 46% at 5 years, *2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years\r\n* OR (C) Southwestern Oncology Group (SWOG) criteria (patient must have 2 risk factors present or one risk factor if this risk factor is a 70–gene signature (GEP70) score of > 37.2) \r\n** 1. Monoclonal spike >= 3 g/dL\r\n** 2. Involved free light chain >= 25 mg/dL\r\n** 3. GEP70 risk score > 37.2 *>= 2 risk factors: high risk of progression at a rate of 70% at 2 years*; we would also include patients with 1 risk factor as long as this risk factor is GEP70 risk score > 37.2 since patients with this risk factor have an intermediate risk of progression at a rate of 50% at 2 years
High risk ET/PV (age > 60; history of thrombosis). Previously treated with at least one other agent (hydroxyurea, interferon, anagrelide) and determined to be either intolerant/resistant
At least one high-risk cytogenetic feature defined by the presence of 17p deletion, 11q deletion and/or p53 mutation
Patients with a history of pulmonary disease or findings present on baseline high-resolution chest CT scan that, in the opinion of the treating investigator, would put the patient at risk of complications of pneumonitis will be excluded
Have a diagnosis of high-risk AML as established by a poor-risk karyotype, poor-risk molecular features, a therapy-related AML, age >= 60 or with antecedent hematologic disorder
Patient is unable to avoid intimate contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) ) for at least 7 days after receiving CRS-207 infusion
High-risk participants who have received chemopreventive drugs in the past are not allowed to enter the study
Intermediate or high-grade: grades 2 or 3 on scale of 1-3
Subjects must have their diagnosis of high-risk AML or high-risk MDS confirmed by pathologic review of bone marrow biopsy according to World Health Organization (WHO) guidelines
We will define subjects as high risk MDS and thus eligible if they have a MD Anderson Comprehensive Cancer MDS Risk Score >= 9
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size > 3cm, early recurrence (<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
Low risk pathologic features (by AJCC 2010 criteria)
Subjects with CLL or SLL who are BTKi intolerant and have received < 6 months of BTKi therapy or are ineligible for BTKi must have failed at least 1 (high-risk) or 2 (standard-risk) other lines of non-BTKi therapy.
Subjects who relapse within 1 year of initial treatment, excluding patients with favorable-risk status according to NCCN Guidelines (NCCN 2015). Favorable-risk cytogenetics: inv(16), t(16;16), t(8;21), t(15;17)
Patient must be stratified/classified into one of the following risk categories:\r\n* The highest risk feature assessed pathologically will determine the patient's category/treatment arm assignment\r\n** Low risk: T1-T2, N0-N1 AND clear (> 3 mm) margins, AND no ECE or PNI/LVI\r\n** High risk: any of the following features: one or more positive margin(s) with any T stage, OR “extensive” (> 1 mm) ECE, OR >= 5 metastatic lymph nodes (regardless of primary tumor margin status)\r\n* Intermediate risk: any of the following features: one or more “close” (< 3 mm) margin(s), OR “minimal” (=< 1 mm) ECE, OR N2a (1 or more lymph node > 3 cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter < 6 cm), OR with perineural invasion or lymphovascular invasion\r\n** Unknown risk: patients found to have N2C or N3 disease on final pathologic analysis are at unknown risk for recurrence, but are not candidates for deintensified adjuvant therapy in this trial; these patients will be treated on Arm C\r\n** Patients not categorized into the appropriate risk category will be considered ineligible for the study
Patients with VS or meningiomas deemed very high surgical risk for stroke and/or other complications by the attending surgeon, such as meningiomas with major vascular or dural sinus infiltration
Non-Hodgkin's lymphoma (NHL): High risk subjects with responsive disease after first relapse. High risk includes those with Burkitt's Lymphoma and those with extensive marrow involvement at diagnosis-precluding autologous transplant.
Hodgkin's disease: High risk subjects with responsive disease after first relapse.
Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with at least one indicator lesion avid on 99mTc-MDP scan will be eligible.
Patients with peripheral blood involvement with white blood count (WBC) > 20,000 or those considered to be at high risk for tumor lysis syndrome (TLS) by high tumor burden are EXCLUDED for the Phase I component of the study
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
Serious chronic or acute illness considered by the principal investigator (PI) to constitute an unwarranted high risk for investigational drug treatment
The patient has either refused or is not considered an appropriate immediate candidate for transplantation and is considered to be at high risk for recurrence by having at least one of the following prognostic factors:
Low and intermediate-risk disease as defined by MIPI score.
Other disorders associated with a high risk of fistula formation, including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea or esophagus
Acute myelogenous leukemia\r\n* Adult: (>= 22 years) >= CR2 OR CR1 with one of the following high risk features\r\n** Adverse or intermediate-risk cytogenetics including:\r\n*** Normal cytogenetics\r\n*** Complex karyotype (> 2 abnormalities)\r\n*** Inv (3) or t(3;3); t(11;19)(q23;p13.1); +13; -17/17p-; -18; -20; (t(6;9); t(6;11); -7, 7q-; -5, 5q-; trisomy 8; t(3;5); t(9:11)(p22q23)\r\n*** Monosomy karyotype (presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality\r\n*** Any other karyotype EXCEPT t(8;21), t(9;11), inv(16), or t(16;16), and M3 (17; 17) unless v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (c-Kit) mutation present and then eligible\r\n*** AML emerging from CML (blast crisis) are eligible\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 myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or cytotoxic chemotherapy\r\n** Hyperleukocytosis (white blood cells [WBC] > 100,000 at diagnosis)\r\n** Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene (FLT3-length mutations [LM]; FLT-internal tandem duplications [ITDs])\r\n** Bilineage or biphenotypic leukemias are high risk features and eligible\r\n* Pediatric (< 22 years): >= CR2 OR CR1 with a high risk feature including\r\n** Primary induction failure (>= 5% blasts in marrow after induction)\r\n** Persistent leukemia (> 15% after first course of chemotherapy)\r\n** Complex karyotype monosomy 7, or -5/-5q, FLT3 ITD-allelic ratio (AR) (> 0.4) EXCEPT if also inv(16)/t(16;16), t(8,21)\r\n** Normal cytogenetics or abnormal cytogenetics EXCEPT if also inv(16)/t(16;16), t(8,21) are eligible for SIBLING transplant only\r\n** Bilineage or biphenotypic leukemias are high risk features and eligible
Have an understanding that the study drug could have a potential teratogenic risk.
CRITERIA FOR ASSIGNMENT TO THE HIGH-RISK ARM OF THE PROTOCOL
Patients with extraneural metastasis are eligible for treatment on the high-risk arm
Intermediate or adverse cytogenetic risk
Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment.
Patients may be eligible after only 1 previous regimen if in a high risk category
Patients with severe SSc as defined by the American College of Rheumatology and at high-risk for a fatal outcome based on the following prognostic factors in groups 1-5:
Pregnancy Prevention Risk Management Plan
Understand that CC-122 could have a potential teratogenic risk.
Must meet any of these criteria for high risk disease:\r\n* Relapse or progressive disease according to uniform response criteria within 2 years after starting first-line therapy or within 2 years after autologous stem cell transplant\r\n* Failure to achieve partial response (PR) within 6 months of staring first-line therapy\r\n* Presence of high risk cytogenetic features (t[14;16], t[14;20], deletion 17p)\r\n* Chromosome 14 translocations other than to chromosome 11\r\n* Chromosome 1p deletion and 1q amplification\r\n* Myeloma Prognostic Risk Score (MyPRS) gene expression score equal or higher than 45.2\r\n* High risk 70 gene expression profile (MyPRS GEP70^TM)\r\n* Any other high risk genetic profile that is determined by future IMWG consensus or by internal myeloma panel consensus; for the latter, any additional criteria will be submitted as an addendum\r\n* Diagnosed with multiple myeloma between the ages of 18-50
Patients with high-risk cytogenetics, t(4:14); t(14;16), t(14:20), deletion p17, gain in 1q, are eligible
Patients with low risk myelofibrosis
High-risk (class 2) uveal melanoma as determined by gene expression profiling (GEP)
After a restaging transurethral resection of bladder tumor (TURBT), patients with histologically proven primary high grade and/or pT1 transitional cell carcinoma of the bladder, with or without pTis and pTis alone are regarded as being at high risk for tumor recurrence and progression
Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance
Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity, non-compliance, or inability to complete the study requirements
Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)
Pregnant women are excluded to avoid the risk of systemic intrauterine/neonatal HSV infection
High risk of inability to comply with therapy in the estimation of the principal investigator (PI)
Any serious medical condition considered by the investigator to constitute an unwarranted high risk for investigational treatment
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
Since induction courses can vary at referring institutions, in cases where the drugs (or doses) are in question, 2 or more members of the study committee will decide on the adequacy of the therapy; likewise, if in cases where high risk status is in question (either based on disease type or risk classification) 2 or more members of the study committee will decide on the adequacy of the therapy
Malignancy at high risk of treatment failure for which autologous hematopoietic stem cell transplantation is considered within standard practice\r\n* Group A: High-risk neuroblastoma \r\n* Group B: Recurrent or refractory Hodgkin lymphoma; recurrent or refractory non-Hodgkin lymphoma\r\n* Group C: High-risk, recurrent or metastatic sarcoma; recurrent or advanced stage Wilms tumor; desmoplastic small round cell tumor; metastatic or recurrent retinoblastoma, high-risk germ cell tumors, and high-risk brain tumors
Patients with isolated hepatic metastasis must satisfy a Clinical Risk Score of 3 or higher
The first 3 patients on the experimental arm will be high risk myeloma and subsequent patients will be low risk myeloma; high risk multiple myeloma patient who have: deletion (del) 17p, del 1p, T (4;14), T (14;16), plasma cell leukemia (PCL), > 1 cytogenetic abnormality, hypodeploid; patients who fail adequate initial therapy (Revlimid, Velcade, dexamethasone [RVD], thalidomide, Velcade, dexamethasone [TVD], or cyclophosphamide, bortezomib, dexamethasone [CyBorD]) and planned to receive non-chemotherapy/cytotoxic salvage regimen (except for single agent cyclophosphamide)
Patients with surgically resected metastatic disease at high risk of relapse are also eligible.
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus
Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to: Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy A co-morbid condition which, in the view of the Investigators, renders the subject at high risk from treatment complications.
Known adverse cytogenetic risk
Known favorable cytogenetic risk
Patients must have diagnostic/pre-treatment specimens obtained within 28 days prior to registration submitted for cytogenetic (and fluorescent in situ hybridization [FISH] if possible) analysis to determine risk status; high risk classification will be defined as del(5q)/-5, del(7q)/-7, abn3q26 [inv(3)/t(3;3)], 11q23 rearrangement [except t(9;11)], 17p-, t(6;9), t(9;22), complex (at least 3 unrelated abnormalities [abn]), and monosomal karyotype (either loss of two different chromosomes or loss of one chromosome along with a structural chromosome abnormality other than add, ring and mar); karyograms and cytogenetics/FISH analysis reports must be submitted for discipline review
Scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
Participants with unrelated adverse events, medical illnesses, or changes in performance status that, per investigator discretion, put them at high risk for continuing participation in the clinical study
Any co-morbid condition that‚ in the view of the attending physician‚ renders the patient at high risk from treatment complications
History of significant disease that in the Investigator's opinion would put the patient at high risk on the trial
Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus
If re-evaluation of a patient’s disease shows unfavorable risk features or intermediate risk features, the patient will be removed from the HOD08 study and consented to the HOD99 or the HOD05 study
Intermediate or high risk disease, defined as stage IB, IIIA, any IV or IA/IIA with “E” lesion(s), 3 or more nodal sites involved, or bulky mediastinal adenopathy
Has factors conferring high risk of relapse.
Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or would put the participants at high risk for treatment-related complications
Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect.
Subject must be either (1) at high risk for candidiasis (1 month - < 2 years ONLY) or (2) have a definitive diagnosis of invasive candidiasis/candidemia (ICC) (All age groups)
Have an understanding that the study drug could have a potential teratogenic risk.
Rhabdomyosarcoma (RMS) \r\n * RMS patients will be eligible if relapse occurs following an autologous transplant or if the patient relapses following initial treatment, but is not eligible for an autologous transplant; patients who do not achieve a CR with initial therapy will also be eligible provided they can be rendered free of bulky disease as defined above\r\n * RMS patients will be eligible in first CR or PR if they present with high-risk disease; high risk disease is defined as stage IV RMS with at least 2 other risk factors listed from the following: \r\n** Bone and/or bone marrow metastases \r\n** Age =< 1 or >= 10 years \r\n** Primary tumor site other than head/neck (except parameningeal) or genitourinary (GU) (except bladder or prostate)
High risk renal cancer per modified UISS criteria
All patients must be diagnosed with neuroblastoma, and categorized as high risk at the time of diagnosis; exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible
No more than 12 months from the date of starting the first induction chemotherapy after diagnosis to the date of ASCT except for the rare occasions as noted below; for tandem ASCT patients, this will be the date of the FIRST stem cell infusion; exception: for those who are initially diagnosed as non-high risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma, the 12 months restriction should start from the date of induction therapy for high risk neuroblastoma (not from the initial induction therapy for non-high risk disease), to the date of ASCT
Patients whom, in the opinion of the treating urologic oncologist, should undergo cystectomy due to high-risk features
High-risk cancer planned for neoadjuvant therapy, full or partial excision of one or both neurovascular bundles
Poor surgical risk (defined as American Society of Anesthesiology Score > 3)
Patients must be at increased risk for cardiotoxicity defined by at least one of the following:\r\n* Previous anthracycline exposure, OR\r\n* 1 or more of the following risk factors for heart disease:\r\n** Left ventricular ejection fraction (LVEF) 50-54% by local echocardiography (ECHO) read\r\n** Age >= 65\r\n** Body mass index (BMI) >= 30 kg/m^2\r\n** Current or prior anti-hypertensive therapy\r\n** Diagnosis of coronary artery disease (CAD)\r\n** Diabetes mellitus\r\n** Atrial fibrillation/flutter
Patient is at high risk for bowel perforation
High-risk patients (as defined by the American College of Sports Medicine risk-stratification schema using the American College of Sports Medicine [ACSM]/American Heart Association exercise pre-participation questionnaire) who do not receive medical clearance from a physician
Any co-morbid condition which, in the view of the principal investigator, renders the patient at high risk from treatment complications
Currently reside in one of the four selected high risk neighborhoods
Patients with high disposition of laryngospasm or apnea
On cytotoxic chemotherapy in the high/moderate/low emetogenic risk categories or oral antineoplastic agents in the high or moderate emetogenic risk categories according to the latest National Comprehensive Cancer Network (NCCN) guideline within 2 weeks of study enrollment
Patients with any co-morbid condition which renders patients at high risk of treatment complication
Patients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with doxorubicin plus ifosfamide (AI) or AI and vincristine (VAI) is indicated
High risk of regurgitation
Have a history of chronic untreated trauma (unrelated to their cancer), psychiatric hospitalization or suicide attempt(s) in the past 5 years, or current moderate to high suicide risk based on our pilot study and other study experience that such patients often require more intensive resources.
High-Risk aGVHD (ARM 1)\r\n* Pediatric or adult hematopoietic cell transplant (HCT) recipients with high-risk acute GVHD, as determined by the refined Minnesota Medical (MN) acute GVHD risk score OR high risk on the basis of blood biomarkers (Ann Arbor score 3); patients in this arm must start treatment within the first 7 days after onset of high-risk aGVHD or
Neurologic and/or orthopedic limitations that preclude the participation in the training program (e.g. bone metastases that may pose a high risk of pathologic fracture)
Patients considered to be high risk for surgical complications will be excluded from the research protocol
Has at least high school education
PHASE I: Women with sporadic cancers (WSC) (does not have hereditary breast/ovarian cancer syndrome [BRCA carrier, strong family history]); if there is any uncertainty, the surgeon will use the Tyrer-Cuzick (Tyrer et al., 2004) risk model to calculate risk; the Tyrer-Cuzick model calculates a personal lifetime risk of breast cancer based on multiple factors; it has become the standard model because it incorporates not only factors such as estrogen exposure and first degree relatives, but also second degree relatives and paternal lineage; a lifetime risk of 20% or greater is considered high risk and would necessitate increased screening methods to the traditional annual mammogram; for this study, anyone with a lifetime risk up to 19% on the Tyrer-Cuzick model will be considered average risk for breast cancer; anyone with a lifetime risk of 20% or greater will be excluded from participation
PHASE II: WSC (does not have hereditary breast/ovarian cancer syndrome [BRCA carrier, strong family history]); if there is any uncertainty, the surgeon will use the Tyrer-Cuzick (Tyrer et al., 2004) risk model to calculate risk; for this study, anyone with a lifetime risk up to 19% on the Tyrer-Cuzick model will be considered average risk for breast cancer; anyone with a lifetime risk of 20% or greater will be excluded from participation
Diagnosis of neuroblastoma as defined by the International Neuroblastoma Risk Group Staging System (INRGSS)
Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after HSCT
AYA meets at least 1 of 3 criteria indicating potentially high palliative care or end-of-life needs:            \r\n* Any high-risk cancer (i.e., metastatic or stage IV)\r\n* Receiving moderate- to high-intensity chemotherapy during 3-5 consecutive days in an in- or out-patient setting\r\n* A diagnosis with an estimated 5-year event-free survival of < 50%
High risk for poor compliance with radiotherapy, humidification, or follow-up as assessed by the investigator
Patients referred for lung cancer screening using a low-dose CT scan modality who are considered high risk by USPSTF guidelines.
BMRI indication: high risk screening per American Cancer Society (ACS) guidelines
Have a 5 year Gail risk of >= 1.67% or 2x risk for age as given in model, or 10 year Tyrer-Cuzick risk 2x population risk as listed in model
MEDICAL ELIGIBILITY CRITERIA FOR PERTAINING TO HIGH RISK GROUPS UNDERGOING RPFNA
High risk population: African American men are at higher risk for prostate cancer compared to that of Caucasian men; this study is targeting the local community which is predominantly African American and thus considered high risk; since this study is being done in the context of a larger community outreach effort, other races and ethnicities will not be excluded, however the majority of the participants will be African American
Phase II: Participants must be asymptomatic, not at increased risk due to family history or personal high risk syndromes
Risk of cancer greater than 60% or less than 20%
Patient must not be suspected of being at high-risk for breast cancer, as defined by the American Cancer Society (ACS) breast MR screening recommendations (lifetime risk of >= 20-25%)
All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
Women must be considered at high risk for breast cancer based on family history (first or second degree relative diagnosed with breast cancer under the age of 60), prior precancerous biopsy or a 5-year Gail model risk estimate of >= 1.7% or 10-year Tyrer-Cuzick risk of 2 x population risk as listed in the model
RANDOMIZED CONTROLLED TRIAL: Utilizing the breast cancer surveillance consortium risk calculator, women will have either (a) an intermediate 5-year risk (> 1.67%-2.49%) and extremely dense breasts or (b) a high 5-year risk (>= 2.50%) and either heterogeneously dense or extremely dense breasts
At high risk of developing breast cancer defined by one or more of the following: Gail model lifetime risk > 20%, a history of deleterious BRCA1/2 mutation or mantle radiation, a history of ductal cancer in situ, or a history of high risk premalignant breast lesion.
Enrolled on the longitudinal high risk cohort study or being seen in the Cancer Prevention Center
High-risk indoor tanner (defined as using an indoor tanning bed at least 10 times in the previous 12 months)
High risk medical condition (e.g. kidney disease)
Projected probability of developing breast cancer by either the Gail model (5-year risk) or the Tyrer–Cuzick model (10-year risk) that is at least 2-fold greater than that for the population; for the Gail model any value of 5-year risk >= 1.67% satisfies the requirement
3. Subjects with breast, lung or pancreatic carcinoma who are at high risk of relapse post definitive therapy at least 4 and no more than 24 weeks from completion of definitive therapy at the time of signing informed consent as described below for each indication:
Have documented or anticipated neutropenia expected to last for at least 7 days, following treatment in at least one of the following clinical situations: acute leukemia, myelodysplasia, severe aplastic anemia, recipients of Autologous hematopoietic stem cell transplant (HSCT), high risk neuroblastoma, advanced stage non-Hodgkin's lymphoma, hemophagocytic lymphohistiocytosis
Subjects who are at high risk for breast cancer will be considered for participation in the study
Subject considered by the Investigator to be high-risk for breast conservation surgery and/or intra-operative radiation therapy
Is receiving chemotherapeutic agent(s) associated with moderate or high risk of emetogenicity, or a chemotherapy regimen not previously tolerated due to vomiting
Has Suicidal Risk Assessment (SRA) scores >= 6
For patients at high risk for developing aGVHD, informed consent should be signed prior to transplant.
High risk benign lesions as the primary pathology diagnosis
Patients who are on anticoagulants or high dose aspirin therapy that cannot be safely stopped for greater than 10 days prior to treatment should be excluded to limit increased risk for urinary obstruction
Patients with low-risk, intermediate-risk and high-risk tumors according to National Comprehensive Cancer Network (NCCN) guidelines (2.2014) will be included
HIGH-RISK POPULATION:
Adult males with unfavorable intermediate- to high-risk localized disease identified as one of the following three categories for unfavorable intermediate-high risk factors, but must have visible disease on baseline MRI of the following:\r\n* Clinical or radiographic T2b-T4 primary tumor\r\n* Gleason score 7-10 in any core\r\n* PSA >= 10 prior to initiation of therapy
Treatment-naïve/ Unfit Cohorts: Previously untreated patients with histological confirmation of AML who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen; or previously untreated patients with intermediate, high, or very high risk MDS. Prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors is allowed.
Extensive prior surgery/radiation present that would render the biopsy highly complex and the risk of intraoperative injury high
Patients at risk for fall or who have had recent fractures
High risk medical condition (e.g. kidney disease, uncontrolled diabetes, etc.)
Any co morbid condition that‚ in the view of the attending physician‚ renders the patient at high risk from ketorolac treatment complications
“High risk” patients
During clinician’s pre-surgical evaluation, presents with high risk for non-therapeutic resection related to cancer diagnosis (PCS study)
Prostate adenocarcinoma with High Risk (HR) and Unfavorable Intermediate Risk (UIR) for recurrence classification as determined by one of the following combinations: o High risk (HR): subjects with one or more of the following risk factors:
N0 o Unfavorable Intermediate Risk (UIR): subjects with no HR features but with one or more of the following adverse risk factors:
Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician
has a substantial risk to progress and cause severe complications.