Downloads: 1
| # | Blank 1 | Frequency | Blank 2 | Frequency | |
|---|---|---|---|---|---|
| 1 | 2 | 16 | involvement | 10 | |
| 2 | 6 | adequate | 8 | studies | 5 |
| 3 | 25 | for patients with solid tumors without known | 5 | 5 | |
| 4 | 1 | has adequate | 3 | involvement peripheral absolute neutrophil count anc > = 1000 / mcL | 3 |
| 5 | 33 | absolute neutrophil count anc > = 1500 unless due to direct | 3 | involvement with lymphoma | 3 |
| 6 | 16 | subjects must have adequate | 2 | involvement of disease | 3 |
| 7 | 47 | absolute neutrophil count > = 1000 / mcL unless due to heavily infiltrated | 2 | involvement by lymphoma | 3 |
| 8 | 50 | subjects with neutrophils < 1500 / mcL or Platelets < 100 000 / mcL with splenomegaly or extensive | 2 | . | 3 |
| 9 | 60 | for subjects with solid tumors without known | 2 | > = 80 cll cell infiltrate | 3 |
| 10 | 85 | absolute neutrophil count anc > = 1000 / mcL unless due to | 2 | involvement . | 2 |
| 11 | 104 | lymphoma participants without | 2 | involvement with > = 5 lymphoblasts | 2 |
| 12 | 3 | hematologic anc 1 . 5 x 109 / l hgb 9 . 0 g / dl and Platelets count 100 x 109 / l Platelets count > = 75 x 109 / l if documented evidence of | 1 | involvement of tumor | 2 |
| 13 | 8 | adequate hematologic function absolute neutrophil count anc 1 . 0 109 / l Platelets count 100 . 0 109 / l and hemoglobin 8 . 0 g / dl patients with | 1 | highly infiltrated with cll cells e . g . > = 80 | 2 |
| 14 | 10 | inadequate | 1 | involvement as the etiology for their cytopenias are eligible | 2 |
| 15 | 11 | patient must have adequate | 1 | and malignancy is documented in the bone marrow | 2 |
| 16 | 17 | 12 . adequate | 1 | involvement are not eligible | 2 |
| 17 | 20 | patients must have adequate | 1 | infiltration do not have to meet hematologic eligibility criteria significant bone marrow infiltration is defined as > = 50 involvement by cll | 2 |
| 18 | 28 | Platelets count > = 50000 / mcL for patients with solid tumors and known | 1 | involvement with disease | 2 |
| 19 | 29 | absolute neutrophil count > = 1000 / mcL unless documented | 1 | involvement are allowed at the investigator s discretion regardless of cytopenias | 2 |
| 20 | 30 | within 10 days of treatment initiation absolute neutrophil count anc > = 1000 / mcL or > = 750 in subjects with | 1 | function defined as Platelets count > = 100 x 109 / l hemoglobin > = 9 . 0 g / dl absolute neutrophil count > = 1 . 5 x 109 / l . | 1 |
| 21 | 32 | absolute neutrophil count anc > = 750 / mcL for subjects without | 1 | reserve consistent with absolute neutrophil count 1 . 5 x 109 / l Platelets count 100 x 109 / l and hemoglobin 9 g / dl without transfusion within 1 week preceding the administration of the study drugs | 1 |
| 22 | 34 | absolute neutrophil count anc 1500 cells / mm3 1 . 5 x 109 / l unless secondary to extensive | 1 | reserve consistent with absolute neutrophil count anc > = 1500 per micro liter / mcL Platelets count > = 100 000 / mcL hemoglobin a1c hba1c less than < 6 . 5 percent . | 1 |
| 23 | 35 | Platelets count 100 000 / mm3 100 x 109 / l unless secondary to extensive | 1 | impairment as evidenced by hemoglobin < 10 . 0 g / dl neutrophil count < 1 . 0 109 / l Platelets < 100 109 / l | 1 |
| 24 | 36 | absolute neutrophil count anc > = 750 / mcL if these cytopenias are not judged by the investigator to be due to underlying disease i . e . potentially reversible with anti neoplastic therapy a subject will not be excluded because of pancytopenia > = grade 3 if it is due to disease based on the resmcLts of | 1 | function as defined below r n absolute neutrophil count 1 . 5x109 / l 1500 per mm3 r n Platelets 100x109 / l 100 000 per mm3 r n hemoglobin > = 9 . 0 g / dl | 1 |
| 25 | 37 | Platelets count > = 50000 / mcL if these cytopenias are not judged by the investigator to be due to underlying disease i . e . potentially reversible with anti neoplastic therapy a subject will not be excluded because of pancytopenia > = grade 3 if it is due to disease based on the resmcLts of | 1 | reserve absolute neutrophil count 1 . 5000 / mcL Platelets count 100 000 / mcL hemoglobin 9 . 0 g / dl . must not have required blood transfusion within 1 week of baseline blood count assessment . | 1 |
| 26 | 38 | absolute neutrophil count anc > = 1000 / mcL r n exception unless documented | 1 | involvement will not be evaluable for hematologic dlt and can enroll with anc 0 . 75 109 / l Platelets count 50 . 0 109 / l and hemoglobin 8 . 0 g / dl | 1 |
| 27 | 40 | absolute neutrophil count anc 750 / mcL r n the above criteria do not have to be met if the patient has | 1 | function for portion a absolute neutrophil count anc 1 . 5 x 109 / l Platelets count 100 x 109 / l hemoglobin > = 9 . 0 g / dl . for portion b anc 1 . 0 x 109 / l Platelets count 75 x 109 / l | 1 |
| 28 | 41 | Platelets count 75000 / mcL r n the above criteria do not have to be met if the patient has | 1 | function per protocol specified hemoglobin Platelets count and absolute neutrophil count | 1 |
| 29 | 43 | anc < 0 . 5000 / mcL or Platelets count < 50000 / mcL unless due to disease involvement in the | 1 | function as evidenced by absolute neutrophil count 1 . 5 10 9 / l hemoglobin > = 9 g / dl patients are allowed to be transfused to this level Platelets 75 10 9 / l | 1 |
| 30 | 44 | Platelets count > = 50000 / mcL in the absence of | 1 | function as assessed by absolute neutrophil count anc 1500 / mm3 hemoglobin 9 . 0 g / dl and Platelets count 100 000 / mm3 . | 1 |
| 31 | 45 | absolute neutrophil count > = 1000 / mcL in the absence of | 1 | reserve absolute neutrophil count anc 1 . 5 x 109 / l . Platelets 100 x 109 / l . hemoglobin 9 g / dl . | 1 |
| 32 | 46 | Platelets count > = 50000 / mcL unless due to heavily infiltrated | 1 | function defined as a hemoglobin > = 9 g / dl absolute neutrophil count anc 1 . 5 10 / l and Platelets count 100 000 / mm . for subjects who received chemotherapy for melanoma just prior to screening for the study subject needs to have a hemoglobin > = 9 g / dl absolute neutrophil count anc > = 2 10 / l | 1 |
| 33 | 48 | absolute neutrophil count 1000 / mcL unless due to disease involvement in the | 1 | function patients must have adequate bone marrow function defined as a peripheral absolute neutrophil count 1000 / µl Platelets count 100 000 / µl transfusion independent and hemoglobin 8 . 0 gm / dl | 1 |
| 34 | 49 | adequate hematologic function Platelets and absolute neutrophil count anc values in accordance with ongoing ibrutinib studies for patients with cll unless cytopenias are due to | 1 | function as assessed by the following hemoglobin > = 9 . 0 g / dl or > = 5 . 6 mmol / l absolute neutrophil count anc > = 1 . 500 / mcL or > = 1 . 5000 / mcL ctcae grade < = 1 Platelets count > = 100 000 / mcL or > = 100 000 / mcL | 1 |
| 35 | 51 | absolute neutrophil count anc > = 750 / mcL r n if these cytopenias are not judged by the investigator to be due to underlying disease i . e . potentially reversible with anti neoplastic therapy a subject will not be excluded because of pancytopenia > = grade 3 if it is due to disease based on the resmcLts of | 1 | function hemoglobin 9 . 0 g / dl Platelets 100 x 109 / l absolute neutrophil count anc 1 . 5 x 109 / l without the use of hematopoietic growth factors . | 1 |
| 36 | 52 | Platelets count > = 50000 / mcL r n if these cytopenias are not judged by the investigator to be due to underlying disease i . e . potentially reversible with anti neoplastic therapy a subject will not be excluded because of pancytopenia > = grade 3 if it is due to disease based on the resmcLts of | 1 | function subjects other than those with aitl as evidenced by absolute neutrophil count 1 . 0 109 / l hemoglobin > = 9 g / dl subjects may be transfused red blood cells to this level . Platelets 50 109 / l | 1 |
| 37 | 53 | absolute lymphocyte count > = 150 / mcL r n if these cytopenias are not judged by the investigator to be due to underlying disease i . e . potentially reversible with anti neoplastic therapy a subject will not be excluded because of pancytopenia > = grade 3 if it is due to disease based on the resmcLts of | 1 | function defined as Platelets count > = 100 x 10 9 / l hemoglobin level > = 9 . 0 g / dl absolute neutrophil count > = 1 . 5 x 10 9 / l | 1 |
| 38 | 55 | diffuse | 1 | function defined as an absolute neutrophil count > = 1 . 5000 / mcL and a Platelets count > = 100 000 / mcL . | 1 |
| 39 | 56 | absolute neutrophil count > = 1000 / mcL unless decreased due to | 1 | absolute neutrophil count anc 1 . 5 x 109 / l hemoglobin hgb 9 g / dl Platelets 100 x 109 / l | 1 |
| 40 | 57 | absolute neutrophil count anc > = 1000 / mcL unless due to disease involvement in the | 1 | function neutrophil count > = / = 1000 / mm3 Platelets count > = / = 75000 / mm3 and hemoglobin concentration > = / = 8 . 0 g / dl . | 1 |
| 41 | 58 | absolute neutrophil count anc > = 1000 / mcL unless deemed related to lymphoma involvement in the | 1 | function defined as an absolute neutrophil count anc of > = > = 1 . 5 109 per liter / l Platelets count > = 100 109 / l and hemoglobin > = 9 gram per deciliter g / dl . receiving transfusions or hematopoietic growth factors to meet enrollment criteria is not allowed within 14 days preceding the first dose of study drug . | 1 |
| 42 | 61 | Platelets count > = 75 10 9 / l > = 30 10 9 / l if myeloma involvement in the | 1 | reserve consistent with absolute neutrophil count anc 1 . 5 10 9 / l Platelets count 100 10 9 / l hemoglobin hgb 9 g / dl . | 1 |
| 43 | 62 | absolute neutrophil count anc > = 1 . 5000 / mcL anc < 1 . 5000 / mcL if cytopenia is due to extensive | 1 | metastatic disease | 1 |
| 44 | 65 | absolute neutrophil count of less than 1000 cells / mcL unless low neutrophil count is thought to be due to malignancy in the | 1 | involvement by lymphoma ie 50 as demonstrated by unilateral bone marrow core biopsy performed during screening or within 3 months prior to signing the icf . in the case of documented extensive bone marrow involvement an anc 1000 cells / mm3 1 . 0 x 109 / l is required . | 1 |
| 45 | 66 | Platelets count less than 30000 / mcL unless low Platelets count is thought to be due to malignancy in the | 1 | involvement by lymphoma ie 50 as demonstrated by unilateral bone marrow core biopsy performed during screening or within 3 months prior to signing the icf . in the case of documented extensive bone marrow involvement a Platelets count of 75000 / mm3 75 x 109 / l is required . | 1 |
| 46 | 67 | patients must have evidence of adequate | 1 | function defined as for patients without bone marrow involvement peripheral absolute neutrophil count anc > = 750 / mcL | 1 |
| 47 | 68 | and patients must have evidence of adequate | 1 | involvement patients with bone marrow involvement only require a Platelets count of > = 30000 / mcL | 1 |
| 48 | 70 | to be performed within 14 days prior to day 1 of protocol therapy absolute neutrophil count anc > = 1000 / mcL r n note growth factor is not permitted within 7 days of anc assessment unless cytopenia is secondary to disease involvement r n exception unless documented | 1 | involvement patients with bone marrow involvement are not required to have a minimum absolute neutrophil count | 1 |
| 49 | 73 | these hematologic function criteria must be met by all patients regardless of | 1 | cellmcLarity of > = 20 with < 5 involvement with tumor | 1 |
| 50 | 75 | Platelets > = 50000 / mcL independent of transfusion support with no active bleeding and absolute neutrophil count > = 1000 / mcL unless due to disease involvement in the | 1 | involvement confirmed by super scans | 1 |
| 51 | 76 | absolute neutrophil count anc > = 1000 / mcL if no | 1 | and felt potentially reversible by the treating physician | 1 |
| 52 | 77 | patients with known | 1 | involvement peripheral absolute neutrophil count anc > = 750 / mcL | 1 |
| 53 | 78 | for patients with solid tumors without | 1 | is > = 50 | 1 |
| 54 | 80 | phase 1 part a patients with known | 1 | involvement of disease as determined by the treating physician | 1 |
| 55 | 81 | Platelets count 50 109 / l 30 109 / l if wm involvement in the | 1 | reserve as shown by absolute neutrophil count anc of at least 1000 / mcL however if the cytopenias are due to extensive bone marrow involvement by cll patients may be included in the study | 1 |
| 56 | 82 | patients with greater than 25 involvement of the | 1 | reserve as shown by Platelets count of at least 50000 / mcL however if the cytopenias are due to extensive bone marrow involvement by cll patients may be included in the study | 1 |
| 57 | 84 | anc 0 . 5000 / mcL or Platelets count 50000 / mcL unless due to disease involvement in the | 1 | function absolute neutrophil count 1500 / µl and Platelets 100 000 / µl | 1 |
| 58 | 86 | patients known to have | 1 | function independent of growth factor support at screening unless clearly due to marrow involvement by cll and / or disease related immune thrombocytopenia if cytopenias are due to disease in the bone marrow any degree of cytopenias are allowed patients with active uncontrolled autoimmune cytopenias are excluded | 1 |
| 59 | 87 | part 1 absolute neutrophil count anc > = 1 . 5000 / mcL part 2 anc > = 1 . 0000 / mcL if there is | 1 | involvement with tumor | 1 |
| 60 | 88 | Platelets count > = 50000 / µl unless due to heavily infiltrated | 1 | involvement r n peripheral absolute neutrophil count anc 750 / mcL | 1 |
| 61 | 90 | absolute neutrophil count > = 1000 / mcL unless in the opinion of the treating physician neutropenia is due to splenomegaly or | 1 | involvement anc > = 800 / mcL if documented bone marrow involvement | 1 |
| 62 | 91 | absolute neutrophil count anc > = 1000 / mcL unless cytopenias due to non hodgkin lymphoma nhl i . e . | 1 | is > = n 50 within 14 days prior to randomization | 1 |
| 63 | 92 | absolute neutrophil count anc > = 1 . 5 10 9 per liter / l and Platelets > = 75 10 9 / l unless cytopenia is caused by the underlying disease i . e . no evidence of additional | 1 | with hl | 1 |
| 64 | 93 | absolute neutrophil count anc > = 500 independent of growth factor support patients who have cytopenias due to significant | 1 | cellmcLarity of > = 20 with < 10 involvement with tumor | 1 |
| 65 | 94 | Platelets count > = 30000 independent of transfusion support patients who have cytopenias due to significant | 1 | involvement with neuroblastoma are eligible provided that minimum anc and Platelets count criteria are met but are not evaluable for hematological toxicity | 1 |
| 66 | 95 | phase ii if the patient had significant | 1 | involvement > = 1 . 5000 / mcL if there is no bone marrow involvement | 1 |
| 67 | 96 | absolute neutrophil count anc < 0 . 75 x 109 / l or Platelets count < 50 x 109 / l unless due to disease involvement in the | 1 | > = 80 cll cell infiltrate and | 1 |
| 68 | 97 | anc < 0 . 75 x 109 / l or Platelets count < 50 x 109 / l unless there is | 1 | involvement or splenomegaly | 1 |
| 69 | 98 | patients with lower values may participate if in the opinion of the investigator the cytopenias are the resmcLt of | 1 | dysfunction e . g . myelodysplastic syndrome hypoplastic bone marrow | 1 |
| 70 | 99 | part a for patients with known | 1 | involvement bone marrow bm plasma cells > = 50 a Platelets count > = 30000 / mcL and absolute neutrophil count anc > = 1000 / mcL is required | 1 |
| 71 | 100 | part b for patients without known | 1 | involvement with active prostate cancer | 1 |
| 72 | 101 | Platelets count > = 100 000 / mcL unless due to | 1 | involvement completed as of amendment 4 | 1 |
| 73 | 102 | adequate baseline Platelets and neutrophil levels must be present unless there is clear evidence of extensive | 1 | infiltration by tumor in which case > = 50000 / ml are allowed | 1 |
| 74 | 103 | minimum absolute neutrophil count of 1000 cells / mcL and minimum Platelets count without transfusion of 20000 / mcL values below these levels may be accepted at the discretion of the pi if thought to be due to | 1 | involvement with tumor infiltration extensive bone marrow involvement is defined as r n bone marrow lymphocytes > = 30 | 1 |
| 75 | 105 | absolute neutrophil count anc > = 1 . 5 unless cytopenias are related to | 1 | involvement by malignancy | 1 |
| 76 | 106 | hemoglobin > = 7 g / dl unless cytopenias are related to | 1 | involvement must have absolute neutrophil count anc > = 1000 / mcL note these criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement | 1 |
| 77 | 107 | absolute neutrophil count anc > = 1 . 5000 / mcL unless due to | 1 | involvement of their tumor with documented blast percentage of > = 5 . | 1 |
| 78 | 108 | all patients must have | 1 | involvement must have r n absolute neutrophil count anc > = 1000 / µl and r n Platelets count > = 50000 / mcL without transfusion support r n note these criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement | 1 |
| 79 | 110 | confirmed | 1 | involvement minimum anc and Platelets levels are not required . | 1 |
| 80 | 111 | absolute neutrophil count > = 1000 / mcL unless due to lymphoma involvement of the | 1 | at the time of study entry | 1 |
| 81 | 113 | absolute neutrophil count > = 1000 / l in absence of | 1 | is > = 50 within 21 days prior to randomization | 1 |
| 82 | 114 | if patient has extensive | 1 | where the minimum anc allowable will be 500 / mcL | 1 |
| 83 | 115 | absolute neutrophil count 1000 / µl unless due to documented leukemic involvement of the | 1 | reserve absolute neutrophil count anc > = 1000 / microliter l Platelets count > = 75000 / l > = 50000 / l for participants with bone marrow involvement and hemoglobin > = 8 gram per deciliter g / dl . | 1 |
| 84 | 116 | Platelets > = 100 000 patients with | 1 | reserve absolute neutrophil count anc > = > = 1000 per micro litre / mcL Platelets count > = 75000 / mcL > = 50000 / mcL for participants with bone marrow involvement and hemoglobin > = 8 gram per deciliter g / dl red blood cell rbc and Platelets transfusion allowed > = 14 days before assessment . | 1 |
| 85 | 117 | absolute neutrophil count anc > = 1200 patients with | 1 | involvement with dlbcl | 1 |
| 86 | 118 | Platelets count 50 10 9 / l 30 10 9 / l if myeloma involvement in the | 1 | involvement of their malignancy confirmed on biopsy completed within 2 weeks prior to start of protocol therapy growth factor allowed to achieve | 1 |
| 87 | 119 | absolute neutrophil count anc > = 1000 / mcL unless deemed likely related to lymphoma involvement in the | 1 | reserve absolute neutrophil count anc > = > = 1000 per cubic millimeter / mcL Platelets count > = 75000 / mcL > = 50000 per micro liter / mcL for participants with bone marrow involvement and hemoglobin > = 8 gram per deciliter g / dl red blood cell rbc transfusion allowed > = 14 days before assessment . | 1 |
| 88 | 122 | absolute neutrophil count anc 1 . 5 x 109 / l or 1 . 0 x 109 / l with | 1 | involvement shomcLd have anc > = 0 . 8000 / mcL and leucocyte count > = 1000 / mcL . | 1 |
| 89 | 123 | absolute neutrophil count > = 1000 / mcL 1 . 0000 / mcL unless they have significant | 1 | reserves as evidenced by n n Platelets > = 100 000 / mm3 100 000 / mcL n n clinically stable hemoglobin > = 9 g / dl 90 g / l and n hematocrit > = 27 without transfusion support n n 10 . normal hepatic function as evidenced by n n bilirubin and alkaline phosphatase less than or equal to 1 x the upper limit of n normal mcLn . n n aspartate aminotransferase ast less than or equal to 75 u / l and alanine n aminotransferase alt less than or equal to 100 u / l . n n albumin > = 3 . 0 g / dl 30 g / l . n n 11 . adequate renal function as evidenced by serum creatinine less than or equal to 1 . 8 n mg / dl 158 umol / l or calcmcLated creatinine clearance > = 50 n ml / min per the cockcroft gamcLt formmcLa with less than 2 protein or 24 hour urine n creatinine clearance > = 50 ml / minute with 24 hour urine protein n less than 1g . n n 12 . provide written informed consent prior to any study specific screening procedures . n n 13 . females may not be lactating or pregnant at screening or baseline n n 14 . all females will be considered to be of childbearing potential unless they are n postmenopausal or have been sterilized surgically n n 15 . male participants must have had a successfmcL vasectomy confirmed azoospermia or they n and their female partner must meet the criteria above n n exclusion criteria n n participants who meet any of the following criteria will be excluded from the study n n 1 . prior denileukin diftitox therapy n n 2 . use of topical steroids within 14 days of day 1 of initial therapy is not allowed n n 3 . active malignancy except for ctcl definitively treated basal or squamous cell n carcinoma of the skin and carcinoma in situ of the cervix within the past 24 months . n n 4 . serious intercurrent illness n n 5 . significant cardiac disease requiring ongoing treatment including congestive heart n failure chf | 1 |
| 90 | 125 | absolute neutrophil count > = 500 / mcL absolute neutrophile count anc values in accordance with ongoing ibrutinib studies for patients with cll unless cytopenias are due to | 1 | function absolute neutrophil count anc > = 1500 / mcL . this anc cannot have been induced or supported by granmcLocyte colony stimmcLating factors . Platelets > = 100 000 / mcL . ii . renal function creatinine 1 . 5 x institutional upper limit normal mcLn . iii . hepatic function bilirubin 1 . 5 x mcLn . sgot ast and sgpt alt 3 . 0 x mcLn and alkaline phosphatase 2 . 5 x mcLn . iv . neurologic function neuropathy sensory and motor less than or equal to grade 1 . | 1 |
| 91 | 126 | absolute neutrophil count anc > = 1 . 0000 / mcL for cohorts 3a and 3b leucocyte count > = 2000 / mcL participants with | 1 | blasts > = 5 for relapsed patients or > = 20 for untreated patients | 1 |
| 92 | 127 | or 2 in the lead in n phase and performance status of 0 or 1 in the main study . n n 8 . life expectancy > = 3 months in the lead in phase and greater n than or equal to 12 months in the main study . n n 9 . adequate | 1 | with no evidence of clonal cll by flow cytometry and / or immunohistochemistry | 1 |
| 93 | 128 | patients must have adequate i . | 1 | NA | |
| 94 | 130 | aml all r n normal values for absolute neutrophil count > = 1000 / microl and Platelets count > = 100 000 / microl r n absence of extramedmcLlary leukemia r n less than 5 percent blast cells present in the | 1 | NA | |
| 95 | 131 | cll r n absence of constitutional symptoms attributable to cll r n no lymph nodes > = 1 . 5 cm in diameter on computed tomography r n no hepatomegaly or splenomegaly by computed tomography r n absolute neutrophil count > = 1500 / microl r n Platelets count > = 100 000 / microl r n no clonal lymphocytes in the peripheral blood by immunophenotyping r n | 1 | NA |