The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)
- Conditions
- Myelodysplastic Syndrome
- Interventions
- Registration Number
- NCT01566695
- Lead Sponsor
- Celgene
- Brief Summary
Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk myelodysplastic syndromes (MDS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 216
- 18 years or older
- Have a documented diagnosis of MDS
- Anemia that requires red blood cell transfusions
- Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Must agree to follow pregnancy precautions as required by protocol.
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted
- Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
- Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide (for lenalidomide : unless the last dose received is >= 8 weeks prior to inclusion into the study).
- Prior allogeneic or autologous stem cell transplant
- Eligible for allogenic or autologous stem cell transplant
- History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect
- Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)
- Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization
- Ongoing medically significant adverse events from previous treatment, regardless of the time period
- Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS)
- Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system is allowed)
- Significant active cardiac disease within the previous 6 months
- Uncontrolled systemic fungal, bacterial, or viral infection
- Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection
- Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
- Abnormal coagulation parameters
- Abnormal liver function test results
- Abnormal kidney function test results
- Known or suspected hypersensitivity to azacitidine or mannitol
- Any significant medical condition, laboratory abnormality, or psychiatric illness
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oral Azacitidine Best Supportiv Care (BSC) Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle. Placebo Placebo Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle. Placebo Best Supportiv Care (BSC) Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle. Oral Azacitidine Oral Azacitidine Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days Each participant was assessed for at least 56 days or more; from the date of randomization of study drug up to the data cut-off date of 25 January 2019, approximately 5 months. RBC transfusion (tfx) independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 56 days (i.e., day 1 to day 56, day 2 to day 57) were considered as a 56-day RBC transfusion independent responder.
- Secondary Outcome Measures
Name Time Method Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days From the date of randomization of study drug up to the data cut-off date of 25 January 2019 Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of ≥ 56 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a ≥ 56 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In the event a participant had more than one ≥56 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis. Participants who maintained RBC TI through the end of the treatment period were censored at the date of treatment discontinuation, death, or 1 day before the start of the subsequent MDS treatment (if any), whichever occurred first, or the particiapnts latest available assessment date in the database if the treatment was still on-going.
Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Time to RBC transfusion independence of ≥ 56 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 56 without any RBC transfusions).
Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo A participant was considered as a RBC transfusion reduction responder if the participant had at least 4 units reduction in transfusion units over any consecutive 56 days period compared to the baseline transfusion units in 56 days.
Percentage of Participants Who Achieved RBC Transfusion Independence for ≥ 84 Days From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo RBC transfusion independence was defined as the absence of any red blood cell (RBC) transfusion during any consecutive "rolling" 84 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 84 days (i.e., day 1 to day 84, day 2 to day 85) were considered as a 84-day RBC transfusion independent responder.
Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of ≥ 84 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a ≥ 84 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In case a participant had more than one ≥84 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis.
Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Time to RBC transfusion independence of ≥ 84 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 84 without any RBC transfusions).
Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Erythroid HI-E improvement was defined as a hemoglobin increase of ≥ 1.5 g/dL; or a reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of ≤ 9.0 g/dL on treatment were counted in the RBC transfusion response evaluation.
Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo HI-P response was defined according to IWG 2006 criteria (Cheson, 2006) and as: 1. Absolute increase of ≥ 30 X 10\^9/L for participants\^ starting with \> 20 X 10\^9/L platelets; 2. Increase from \< 20 X 10\^9/L to \> 20 X 10\^9/L and by at least 100%. HI-P must have lasted at least 8 weeks.
Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of ≥ 8 Weeks (56 Days) From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Platelet transfusion independence was defined as the absence of any platelet transfusion during any consecutive "rolling" 56 days during the treatment period, (ie, Day 1 to 56, Day 2 to 57, Days 3 to 58, etc.). Participants were considered platelet transfusion dependent at baseline if they had received ≥ 2 platelet transfusions during the 56 days immediately preceding randomization and had no consecutive 28-day period during which no platelet transfusions were administered.
Time to Platelet Transfusion Independence From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Time to platelet transfusion independence was defined as the time between randomization and the first documented date of onset of transfusion independence (ie, Day 1 of 56 without any platelet transfusions).
Overall Survival (OS) From randomization up to death from any cause; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Overall survival was defined as the time from randomization to death from any cause and was calculated using randomization date and date of death, or date of last follow-up for censored participants. All subjects were followed until drop out (withdrawal of consent from further data collection or lost to follow-up), death, or study closure. Participants who dropped out or were alive at study closure (or at the time of the interim analysis) had their OS times censored at the time of last contact, as appropriate.
Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS Response was assessed every 3 cycles; up to the data cut-off date of 25 Jan 2019; median duration of exposure to oral azacitidine was 86.0 days and 119.0 days for placebo Hematologic response was defined as: • A complete response (CR): \<5% myeloblasts, and normal maturation of all cell lines; Peripheral blood (PB) shows: hemoglobin \>10 g/dL, neutrophils ≥1.0x10\^9/L, platelets ≥100x10\^9/dL, blasts (0%) • Partial Response (PR): same as CR bone marrow (BM) shows blasts decreased by ≥ 50% over pre-treatment but still \> 5%; Cellularity and morphology not relevant • Marrow CR: BM: ≤ 5% myeloblasts and decrease by ≥ 50% over pre-treatment PB • Stable disease (SD): failure to achieve at least PR, but no evidence of progression for \> 8 wks • Failure: death during treatment or disease progression • Disease Progression for those with: - Less than 5% blasts: ≥ 50% increase in blasts to \> 5% blasts - 5%-10% blasts:≥ 50% increase to \> 10% blasts - 10%-20% blasts:≥ 50% increase to \> 20% blasts - 20%-30% blasts ≥ 50% increase to \> 30% blasts Any of the following: - ≥ 50% decrease from maximum remission/response in granulocytes or platelets
Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML) From randomization of study drug to the end up to final data cut-off date of 25 January 2019; maximum follow-up time was 67.9 months for azacitidine and 64.8 months for placebo group Participants with a documented diagnosis of AML arising from previous MDS documented diagnosis.
Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML From randomization of study drug to progression of AML; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Time to AML progression was defined as the time from the date of randomization until the date the subject has documented progression to AML. For participants who had progression to AML documented in MLL central lab report, the earliest sample collection date with the diagnosis of "s-AML arising from previous MDS" was used as the date to AML progression.
Percentage of Participants With Significant Bleeding Events From date of randomization until 28 days after the last dose of IP; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo Clinically significant bleeding event was defined as: any intracranial or retroperitoneal bleed; bleeding requiring transfusions of \> 2 units of blood/blood products; bleeding associated with a decrease in hemoglobin of \> 2 g/dL; or bleeding from any site requiring transfusions of \> 2 units of blood.
Number of Participants With Treatment Emergent Adverse Events (TEAE) From first dose of IP up to 28 days after the last dose of IP or until the last study visit; up to a maximum of approximately 6 months on study A TEAE was defined as an adverse event that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. A serious adverse event (SAE) is any: • Death; • Life-threatening event; • Any inpatient hospitalization or prolongation of existing hospitalization; • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect; • Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-G and FACT-An score are summed to form the FACT-An total score. The FACT-An Trial Outcome Index (TOI) consists of the summation of a "summary scale" and includes the Physical Well-being, (PWB; 7 items; score range, 0-28), the Functional Well-being (7 items; score range, 0-28) and the Anemia subscale consisting of 20 items on the same five-point scale, with 13 of them measuring fatigue related symptoms (FS) and seven measuring non-FS. The FACT-An TOI has been demonstrated to be a sensitive indicator of clinical outcomes in a number of diseases including MDS. The Fact-TOI score ranges from 0 to 136. Higher scores on all scales of the Fact-An and subscales on the FACT-TOI reflect better quality of life or fewer symptoms.
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-An is a 47-item, cancer-specific questionnaire consisting of a core 27-item general questionnaire (i.e., the Functional Assessment of Cancer Therapy-General \[FACT-G\]) The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are: • Physical Well-being (PWB; 7 items; score range, 0-28), • Social/Family Well-being (SWB; 7 items; score range, 0-28), • Emotional Well-being (EWB; 6 items; score range, 0-24), and • Functional Well-being (7 items; score range, 0-28). The FACT-G is a summation composed of a "summary scale" including the PWB, SWB, EWB and FWB. The FACT-G score range is from 0 to 108. For all summary scales including FACT-G, a higher score indicates better HRQoL or lower level of symptoms.
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6 Baseline to Cycle 6 Day 1 The FACT-G and the anemia subscale (AnS) are summed to form the FACT-An total score and the total score ranges from 0 to 188. The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are: • Physical Well-being (PWB; 7 items; score range, 0-28), • Social/Family Well-being (SWB; 7 items; score range, 0-28), • Emotional Well-being (EWB; 6 items; score range, 0-24), and • Functional Well-being (7 items; score range, 0-28). The AnS consists of 20 items on the same 5-point scale, with 13 of them measuring fatigue-related symptoms (FS) and 7 measuring non-FS. The AnS and FS scores can range from 0-80 and 0-52, respectively. For all domains and summary subscales, a higher score indicates better HRQoL or lower level of symptoms.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index Subscale Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General Subscale Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With a Clinically Meaningful Improvement (CMI) From Baseline in the Functional Assessment of Cancer Therapy Anemia-Total Score Domain Within the FACT-An Instrument at Cycle 6 Cycle 6 Day 1 A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 2 Day 1 (C2D1) From Baseline to Cycle 2 Day 1 (C2D1) The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 3 Day 1 (C3D1) From Baseline to Cycle 3 Day 1 (C3D1) The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 4 Day 1 (C4D1) From Baseline to Cycle 4 Day 1 (C4D1) The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 5 Day 1 (C5D1) From Baseline to Cycle 5 Day 1 (C5D1) The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 6 Day 1 (C6 D1) From Baseline to Cycle 6 Day 1 (C6 D1) The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 7 Day 1 (C7D1) From Baseline to Cycle 7 Day 1 (C7D1) The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - End of Treatment From Baseline to End of Treatment The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved \[i.e., change score from 1 to 4\], no change \[0\], worsened by one level \[-1\], worsened by ≥2 levels \[-2 to -4\], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6 From Baseline to Cycle 6 Day 1 The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved \[by ≥1 level\], no change, worsened \[by ≥1 level\], and missing) from baseline are reported.
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6 From Baseline to Cycle 6 Day 1 The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved \[by ≥1 level\], no change, worsened \[by ≥1 level\], and missing) from baseline are reported.
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6 From Baseline to Cycle 6 Day 1 TThe EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved \[by ≥1 level\], no change, worsened \[by ≥1 level\], and missing) from baseline are reported.
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6 From Baseline to Cycle 6 Day 1 The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved \[by ≥1 level\], no change, worsened \[by ≥1 level\], and missing) from baseline are reported.
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6 From Baseline to Cycle 6 Day 1 The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved \[by ≥1 level\], no change, worsened \[by ≥1 level\], and missing) from baseline are reported.
Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo The number of reasons for hospitalizations and hospital admissions during the treatment period were monitored and include those associated with: AEs, protocol-driven procedures, transfusions, non-protocol procedures, elective procedures or those associated with social, practical or technical reasons in the absence of AEs. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo The total number of days hospitalized due to any reason during the treatment period was monitored. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo The number of days hospitalized per total patient years. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Trial Locations
- Locations (196)
Local Institution - 942
🇺🇸New Haven, Connecticut, United States
Local Institution - 917
🇺🇸Portland, Oregon, United States
Local Institution - 924
🇺🇸Houston, Texas, United States
Local Institution - 904
🇺🇸Seattle, Washington, United States
Alta Bates Comprehensive Cancer Center
🇺🇸Berkeley, California, United States
Tower Hematology/Oncology Medical Group and Tower Cancer Research Found
🇺🇸Beverly Hills, California, United States
City Of Hope
🇺🇸Duarte, California, United States
California Cancer Associates for Research and Excellence cCARE
🇺🇸Escondido, California, United States
Marin Oncology Associates
🇺🇸Greenbrae, California, United States
UCSD-Thornton Hospital
🇺🇸La Jolla, California, United States
University of Southern California Norris Cancer Center
🇺🇸Los Angeles, California, United States
University of Florida Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Phoebe Cancer Center of Phoebe Putney Memorial Hospital
🇺🇸Albany, Georgia, United States
Robert H Lurie Comprehensive Cancer Center NW Univ
🇺🇸Chicago, Illinois, United States
University Of Illinois At Chicago
🇺🇸Chicago, Illinois, United States
University Of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Loyola University Chicago
🇺🇸Maywood, Illinois, United States
University Of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Louisville, J.G. Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Hematology And Oncology Specialists, Llc
🇺🇸Metairie, Louisiana, United States
Johns Hopkins Medicine
🇺🇸Baltimore, Maryland, United States
UMASS Memorial Hospital
🇺🇸Worcester, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Jackson Oncology Associates PLLC
🇺🇸Jackson, Mississippi, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Kansas City VA Medical Center University of Kansas Medical Center
🇺🇸Kansas City, Missouri, United States
University Of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Weill Cornell Medical College - New York - Presbyterian Hospital
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai Medical Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Eastern Institute of Medical Sciences
🇺🇸Greenville, North Carolina, United States
University Hospitals of Cleveland Case Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Penn Medicine: University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
Western Pennsylvania Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Brooke Army Medical Center Francis Street Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Local Institution - 900
🇺🇸Houston, Texas, United States
Millennium Physicians - Oncology
🇺🇸Houston, Texas, United States
VA Commonwealth University - Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Waukesha Memorial Hospital
🇺🇸Waukesha, Wisconsin, United States
Local Institution - 137
🇦🇺Garran, Australian Capital Territory, Australia
Local Institution - 129
🇦🇺Adelaide, South Australia, Australia
Local Institution - 134
🇦🇺Clayton, Victoria, Australia
Local Institution - 132
🇦🇺Frankston, Victoria, Australia
Local Institution - 131
🇦🇺Camperdown, Australia
Local Institution - 127
🇦🇺Epping, VIC, Australia
Local Institution - 133
🇦🇺Fitzroy, Australia
Local Institution - 135
🇦🇺Kogarah, Australia
Local Institution - 130
🇦🇺Malvern, Australia
Local Institution - 126
🇦🇺Milton, Brisbane, Australia
Local Institution - 138
🇦🇺Waratah, Australia
Local Institution - 136
🇦🇺Woolloongabba, Australia
Local Institution - 203
🇧🇪Brasschaat, Belgium
Local Institution - 200
🇧🇪Brugge, Belgium
Local Institution - 202
🇧🇪Charleroi, Belgium
Local Institution - 201
🇧🇪Leuven, Belgium
Local Institution - 154
🇧🇷Fortaleza, Ceará, Brazil
Local Institution - 155
🇧🇷Curitiba, Paraná, Brazil
Local Institution - 152
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Local Institution - 153
🇧🇷Rio De Janeiro, Brazil
Local Institution - 151
🇧🇷Sao Paulo, Brazil
Local Institution - 182
🇨🇦Edmonton, Alberta, Canada
Local Institution - 178
🇨🇦Vancouver, British Columbia, Canada
Local Institution - 183
🇨🇦Barrie, Ontario, Canada
Local Institution - 180
🇨🇦Hamilton, Ontario, Canada
Local Institution - 179
🇨🇦Toronto, Ontario, Canada
Local Institution - 176
🇨🇦Toronto, Ontario, Canada
Local Institution - 181
🇨🇦Montreal, Quebec, Canada
Local Institution - 177
🇨🇦Montreal, Quebec, Canada
Local Institution - 226
🇨🇿Brno, Jihomoravský Kraj, Czechia
Local Institution - 230
🇨🇿Hradec Králové, Czechia
Local Institution - 229
🇨🇿Olomouc, Czechia
Local Institution - 228
🇨🇿Praha, Czechia
Local Institution - 227
🇨🇿Praha, Czechia
Local Institution - 253
🇩🇰Aarhus, Denmark
Local Institution - 252
🇩🇰Odense C, Denmark
Local Institution - 251
🇩🇰Roskilde, Denmark
Local Institution - 276
🇫🇮Helsinki, Finland
Local Institution - 277
🇫🇮Turku, Finland
Local Institution - 305
🇫🇷Lille, France
Local Institution - 304
🇫🇷Marseille Cedex 9, France
Local Institution - 301
🇫🇷Nantes, France
Local Institution - 308
🇫🇷Paris, France
Local Institution - 307
🇫🇷Pierre-Bénite Cedex, France
Local Institution - 302
🇫🇷Rennes Cedex, France
Local Institution - 303
🇫🇷Rouen Cedex, France
Local Institution - 306
🇫🇷Strasbourg, France
Local Institution - 300
🇫🇷Toulouse Cedex 9, France
Local Institution - 309
🇫🇷Tours, France
Local Institution - 350
🇩🇪Dresden, Germany
Local Institution - 361
🇩🇪Dresden, Germany
Local Institution - 359
🇩🇪Duesseldorf, Germany
Local Institution - 355
🇩🇪Dusseldorf, Germany
Local Institution - 356
🇩🇪Hamburg, Germany
Local Institution - 353
🇩🇪Keil, Germany
Local Institution - 351
🇩🇪Leipzig, Germany
Local Institution - 352
🇩🇪München, Germany
Local Institution - 357
🇩🇪Tubingen, Germany
Local Institution - 360
🇩🇪Ulm, Germany
Local Institution - 853
🇬🇷Heraklion, Irakleio, Greece
Local Institution - 851
🇬🇷Alexandroupolis, Greece
Local Institution - 852
🇬🇷Athens, Greece
Local Institution - 855
🇬🇷Athens, Greece
Local Institution - 850
🇬🇷Athens, Greece
Local Institution - 854
🇬🇷Patras, Greece
Local Institution - 452
🇮🇱Tel-Aviv, Tel Aviv, Israel
Local Institution - 453
🇮🇱Haifa, Israel
Local Institution - 451
🇮🇱Petach Tikva, Israel
Local Institution - 454
🇮🇱Tel Hashomer, Israel
Local Institution - 482
🇮🇹Alessandria, Italy
Local Institution - 492
🇮🇹Bari, Italy
Local Institution - 489
🇮🇹Bologna, Italy
Local Institution - 494
🇮🇹Cagliari, Italy
Local Institution - 486
🇮🇹Firenze, Italy
Local Institution - 479
🇮🇹Lecce, Italy
Local Institution - 488
🇮🇹Milano, Italy
Local Institution - 498
🇮🇹Milan, Italy
Local Institution - 497
🇮🇹Novara, Italy
Local Institution - 480
🇮🇹Palermo, Italy
Local Institution - 495
🇮🇹Pavia, Italy
Local Institution - 496
🇮🇹Pisa, Italy
Local Institution - 485
🇮🇹Reggio Calabria, Italy
Local Institution - 484
🇮🇹Rionero in Vulture, Italy
Local Institution - 487
🇮🇹Roma, Italy
Local Institution - 490
🇮🇹Roma, Italy
Local Institution - 481
🇮🇹Roma, Italy
Local Institution - 499
🇮🇹Terni, Italy
Local Institution - 477
🇮🇹Torino, Italy
Local Institution - 493
🇮🇹Torrette Di Ancona, Italy
Local Institution - 478
🇮🇹Udine, Italy
Local Institution - 476
🇮🇹Venezia - Mestre, Italy
Local Institution - 704
🇰🇷Busan, Korea, Republic of
Local Institution - 703
🇰🇷Daegu, Korea, Republic of
Local Institution - 701
🇰🇷Seoul, Korea, Republic of
Local Institution - 702
🇰🇷Seoul, Korea, Republic of
Local Institution - 700
🇰🇷Seoul, Korea, Republic of
Local Institution - 830
🇲🇽Huixquilucan de Degollado, Mexico
Local Institution - 828
🇲🇽Monterrey, Mexico
Local Institution - 829
🇲🇽Monterrey, Mexico
Local Institution - 827
🇲🇽Tlalpan, Mexico
Local Institution - 528
🇳🇱Amsterdam, Netherlands
Local Institution - 527
🇳🇱Groningen, Netherlands
Local Institution - 526
🇳🇱Nijmegen, Netherlands
Local Institution - 529
🇳🇱Rotterdam, Netherlands
Local Institution - 552
🇳🇴Førde, Norway
Local Institution - 551
🇳🇴Oslo, Norway
Local Institution - 582
🇵🇱Bydgoszcz, Poland
Local Institution - 576
🇵🇱Gdansk, Poland
Local Institution - 579
🇵🇱Krakow, Poland
Local Institution - 581
🇵🇱Lodz, Poland
Local Institution - 580
🇵🇱Torun, Poland
Local Institution - 583
🇵🇱Warszawa, Poland
Local Institution - 577
🇵🇱Warszawa, Poland
Local Institution - 578
🇵🇱Wroclaw, Poland
Local Institution - 604
🇵🇹Beja, Portugal
Local Institution - 600
🇵🇹Coimbra, Portugal
Local Institution - 601
🇵🇹Lisboa, Portugal
Local Institution - 603
🇵🇹Lisboa, Portugal
Local Institution - 602
🇵🇹Porto, Portugal
Local Institution - 626
🇪🇸Badalona (Barcelona), Spain
Local Institution - 635
🇪🇸Barcelona, Spain
Local Institution - 625
🇪🇸Barcelona, Spain
Local Institution - 636
🇪🇸Granada, Spain
Local Institution - 629
🇪🇸Madrid, Spain
Local Institution - 634
🇪🇸Madrid, Spain
Local Institution - 631
🇪🇸Madrid, Spain
Local Institution - 632
🇪🇸Malaga, Spain
Local Institution - 628
🇪🇸Oviedo, Spain
Local Institution - 630
🇪🇸Salamanca, Spain
Local Institution - 627
🇪🇸Seville, Spain
Local Institution - 633
🇪🇸Vitoria-Gasteiz, Álava, Spain
Local Institution - 653
🇸🇪Goeteborg, Sweden
Local Institution - 652
🇸🇪Lund, Sweden
Local Institution - 651
🇸🇪Stockholm, Sweden
Local Institution - 401
🇹🇷Adana, Turkey
Local Institution - 405
🇹🇷Antalya, Turkey
Local Institution - 403
🇹🇷Istanbul, Turkey
Local Institution - 400
🇹🇷Istanbul, Turkey
Local Institution - 404
🇹🇷Mersin, Turkey
Local Institution - 402
🇹🇷Trabzon, Turkey
Local Institution - 685
🇬🇧Oxford, Oxfordshire, United Kingdom
Local Institution - 687
🇬🇧Aberdeen, United Kingdom
Local Institution - 691
🇬🇧Birmingham, United Kingdom
Local Institution - 686
🇬🇧Bristol, United Kingdom
Local Institution - 689
🇬🇧Cambridge, United Kingdom
Local Institution - 678
🇬🇧Cardiff, United Kingdom
Local Institution - 688
🇬🇧Harrow Middlesex, United Kingdom
Local Institution - 692
🇬🇧Hull, United Kingdom
Local Institution - 677
🇬🇧Leicester, United Kingdom
Local Institution - 683
🇬🇧Liverpool, United Kingdom
Local Institution - 676
🇬🇧London, United Kingdom
Local Institution - 684
🇬🇧London, United Kingdom
Local Institution - 679
🇬🇧Manchester, United Kingdom
Local Institution - 681
🇬🇧Nottingham, United Kingdom
Local Institution - 690
🇬🇧Sutton in Ashfield, United Kingdom
Local Institution - 680
🇬🇧Wolverhampton, United Kingdom