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)