An Open-Label Study of Defibrotide for the Prevention of Acute Graft-versus-Host-Disease (AGvHD)
- Conditions
- Graft-versus-host DiseaseAcute-graft-versus-host Disease
- Interventions
- Drug: Standard of Care
- Registration Number
- NCT03339297
- Lead Sponsor
- Jazz Pharmaceuticals
- Brief Summary
This is a study comparing the defibrotide prophylaxis arm vs standard of care arm for the prevention of aGvHD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 152
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Participant must be ≥1 year of age at screening and undergoing allogeneic Hematopoietic Stem Cell Transplant (HSCT).
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Participant must be diagnosed with acute leukemia in morphologic complete remission (CR1 or CR2) or with Myelodysplastic syndrome (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow
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Participant must have planned to receive either a myeloablative or reduced-intensity conditioning regimen and have an unrelated donor who is human leukocyte antigen (HLA) matched or single-allele mismatched
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Participant must receive the following medical regimen as part of standard of care immunoprophylaxis for GvHD in either study arm at doses and regimen determined by local institutional guidelines, physician preference, and participant need:
Methotrexate (MTX) or Mycophenolate mofetil (MMF) + calcineurin inhibitor (Cyclosporine A [CSA] or Tacrolimus [TAC]) +/- Anti-thymocyte globulin (ATG) (ATG use is limited to 30% of participants).
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Graft must be a CD3+ T-cell replete peripheral blood stem cell (PBSC) graft or non-manipulated bone marrow (BM) graft.
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Adult participants must be able to understand and sign a written informed consent. For pediatric participants, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
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Participant has had a prior autologous or allogeneic HSCT.
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Participant is using or plans to use an investigational agent for the prevention of GvHD.
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Participant is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study.
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Participant, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
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Participant has a psychiatric illness that would prevent the participant or legal guardian or representative from giving informed consent and/or assent.
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Participant has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study.
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Participant is pregnant or lactating and does not agree to stop breastfeeding.
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Any other condition that would cause a risk to the participant if he/she participated in the trial.
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Participant has a known history of hypersensitivity to defibrotide or any of the excipients.
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Participant had acute bleeding that is clinically significant within 24 hours before the start of study treatment, defined as either of the following:
- Hemorrhage requiring >15 cc/kg of packed red blood cells (eg, pediatric participant weighing 20 kg and requiring 300 cc packed red blood cells/24 hours, or an adult weighing >70 kg and requiring 3 units of packed red blood cells/24hours) to replace blood loss, or
- Bleeding from a site which, in the investigator's opinion, constituted a potential life-threatening source (eg, pulmonary hemorrhage or central nervous system bleeding), irrespective of amount of blood loss
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Participant used any medication that increases the risk of bleeding within 24 hours before the start of study treatment, including, but not limited to, systemic heparin, low molecular weight heparin, heparin analogs, alteplase, streptokinase, urokinase, antithrombin III, oral anticoagulants including warfarin, and other agents that increase the risk of bleeding. Participants may have received heparin or other anticoagulants for routine central venous line management and intermittent dialysis or ultrafiltration. Fibrinolytic instillation for central venous line occlusion was also permitted. Note: Heparin used to keep catheters open was allowed (up to 100 U/kg/day).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Defibrotide Prophylaxis Defibrotide Standard of Care Immunoprophylaxis + Defibrotide Defibrotide Prophylaxis Standard of Care Standard of Care Immunoprophylaxis + Defibrotide Standard of Care Standard of Care Standard of Care Immunoprophylaxis Alone
- Primary Outcome Measures
Name Time Method Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) HSCT Day (Day +0 post-HSCT) through Day +100 post-HSCT Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the International Bone Marrow Transplant Registry (IBMTR) Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years Baseline through Day +100 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years Baseline through Day +180 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years Baseline through Day +100 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Days +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years Baseline through Day +180 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years Baseline through Day +100 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes as Measured Based on the EQ Visual Analog Scale (EQ VAS) Baseline through Days +100 and +180 post-HSCT The EQ VAS score at baseline and each of the post-HSCT assessments was summarized and presented using descriptive statistics. A higher EQ VAS score represents better QoL. For each of the post-HSCT assessments, change between baseline and that assessment in the EQ VAS score was calculated similarly to the EQ-5D-5L index value for a specific participant and was summarized and presented using descriptive statistics. The score ranges from a minimum of 0 and a maximum of 100. A negative change in the score indicates a decrease in quality of life.
Cumulative Incidence Percentage of Grade B to D aGvHD by Day +180 Post-HSCT HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the IBMTR Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days Post-HSCT HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT For each treatment arm, the cumulative incidence rate of systemic steroid use for the treatment of aGvHD by Day +180 post-HSCT will be estimated using the cumulative incidence competing risk estimator. The calculation of the cumulative incidence rates and the stratified Gray's test was carried out using the LIFETEST procedure in SAS version 9.4. If the participant experienced a competing risk event, then the initiation date was used to calculate the time-to-event variable.
Change From Baseline to Days +100 and +180 Post-HSCT in the Physical Wellbeing Subscale as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score Baseline through Days +100 and +180 post-HSCT The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT physical wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score Baseline through Days +100 and +180 post HSCT The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT functional wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score Baseline through Days +100 and +180 post-HSCT The FACT-General (FACT-G) is a core component of the FACT-BMT, and includes 4 of the 5 subscales included in the FACT-BMT total score (FACT physical wellbeing score, FACT social/family wellbeing score, FACT emotional wellbeing score, the FACT functional wellbeing score). In line with this similarity, results of the FACT-G exhibited the same pattern as described for the FACT-BMT total score. The FACT-G scores range from a minimParticipants were age ≥16 years at baseline.
Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by Days +100 and +180 Post-HSCT HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT Grade B to D aGvHD was defined using the IBMTR Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Cumulative Incidence Percentage of Grade C to D aGvHD by Days +100 and +180 Post-HSCT HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT Cumulative Incidence Percentage of Grade C to D aGvHD was defined using the IBMTR Severity Index. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Cumulative Incidence Percentage of Disease Relapse by Days +100 and +180 Post-HSCT HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT Disease relapse was defined by either morphological evidence of acute leukemia or Myelodysplastic syndrome (MDS) consistent with pre-transplant features, documented or not by biopsy. The event was defined as an increase in size of prior sites of disease or evidence of new sites of disease, documented or not by biopsy. Disease relapse was diagnosed when there was morphological or clinical evidence of the following: reappearance of leukemia blast cells in the peripheral blood, or \>5% blasts in the bone marrow (BM), not attributable to another cause (eg, BM regeneration), or the appearance of previous or new dysplastic changes (MDS specific) within the BM, with or without falling donor chimerism, or the development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid, or institution of therapy to treat relapsed disease, including donor lymphocyte infusion.
Change From Baseline to Days +100 and +180 Post-HSCT in the Social/Family Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score Baseline through Days +100 and +180 post-HSCT The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT social/family wellbeing subscale scores range from a minimum of 0 to a maximum of 28, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Change From Baseline to Days +100 and +180 Post-HSCT in the Emotional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score Baseline through Days +100 and +180 post-HSCT The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT emotional wellbeing subscale scores range from a minimum of 0 to a maximum of 24, with higher scores indicating better quality of life.
Change From Baseline to Days +100 and +180 Post-HSCT in the Bone Marrow Transplantation Subscale (BMTS) as Measured by the FACT-BMT Questionnaire Score Baseline through Days +100 and +180 post-HSCT The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT-BMT subscale scores range from a minimum of 0 to a maximum of 40, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Change From Baseline to Days +100 and +180 Post-HSCT in the FACT-BMT Total Score Baseline through Days +100 and +180 post-HSCT The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) total score is the sum of the FACT physical wellbeing score, the FACT social/family wellbeing score, the FACT emotional wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. The FACT-BMT total score range is from a minimum of 0 to a maximum of 148, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant-Trial Outcomes Index (FACT-BMT-TOI) Baseline through Days +100 and +180 post-HSCT The FACT-BMT-TOI is defined as the sum of the FACT physical wellbeing score, the FACT functional wellbeing score, and the FACT-BMT subscale. Scores range from a minimum of 0 to a maximum of 96, with higher scores indicating better quality of life. A negative change from baseline indicates a decrease in score.
Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes Measured Based on the EQ-5D-5L Index Value for Health States Baseline through Days +100 and +180 post-HSCT The 5-Level EuroQol-5D health questionnaire (EQ-5D-5L) index value, which is country-specific, was only performed for participants in the US. The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Change from the baseline assessment to Days +100 and +180 post-HSCT in the index value was assessed. The index value total range is from a minimum value of -1 to a maximum value of +1. A higher EQ-5D-5L index value represents better quality of life (QoL), thus a positive change in the index value represents improved QoL.
Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years Baseline through Day +180 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years Baseline through Day +100 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years Baseline through Day +180 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years Baseline through Day +100 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +100 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years Baseline through Day +180 post-HSCT The EQ-5D-5L is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of the 5 dimensions based on the descriptive system of the EQ-5D-5L, the numbers of participants for all categories (the 5 levels of reported problems) were assessed. For Day +180 Post-HSCT change between baseline in each dimension will be categorized as follows for a specific participant: Condition improved, if the reported level of problem is lower at that assessment than at baseline; Condition unchanged, if the reported level of problem remains the same; Condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; Unknown, if the reported level of problem is not completed or missing either at baseline or at that assessment.
Trial Locations
- Locations (62)
Universitätsklinikum Innsbruck
🇦🇹Innsbruck, Austria
Klinichki Bolnicki Centar Zagreb
🇭🇷Zagreb, Croatia
Uniklinik Köln
🇩🇪Köln, Germany
University Medicine Göttingen Germany
🇩🇪Göttingen, Germany
Klinikum Frankfurt (Oder) GmbH
🇩🇪Brandenburg, Germany
Medizinische Universitätsklinik Knappschaftskrankenhaus
🇩🇪Bochum, Germany
Universitatsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinikum Mannheim Universitätsklinikum gGmbH
🇩🇪Mannheim, Germany
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico
🇪🇸Salamanca, Spain
CHRU Lille
🇫🇷Lille, France
McGill University Health Center
🇨🇦Montreal, Canada
UZ Gent
🇧🇪Gent, Belgium
Hospital d Instructions des Armees Percy
🇫🇷Clamart, France
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
University General Hospital of Patras
🇬🇷Patras, Greece
Helios Klinikum Berlin Buch
🇩🇪Berlin, Germany
Hospital Universitario Marques de Valdecilla
🇪🇸Coruña, Spain
Institut Gustave Roussy
🇫🇷Villejuif, France
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
🇮🇹Milano, Italy
St James University Hospital
🇬🇧Leeds, United Kingdom
Universitätsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Halle (Saale)
🇩🇪Halle, Germany
Attikon University General Hospital
🇬🇷Athens, Greece
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Madrid, Spain
Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
🇵🇱Wrocław, Poland
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Stanford University
🇺🇸Palo Alto, California, United States
Mayo Clinic Jacksonville - PPDS
🇺🇸Jacksonville, Florida, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Hôpital Maisonneuve-Rosemont
🇨🇦Montreal, Canada
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States
Ordensklinikum Linz, Krankenhaus der Elisabethinen GmbH
🇦🇹Linz, Austria
Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
🇧🇬Sofia, Bulgaria
Sainte Justine Hospital
🇨🇦Montreal, Canada
Institut Universitaire du Cancer de Toulouse - Oncopole
🇫🇷Toulouse, France
Klinikum rechts der Isar der Technischen Universität München
🇩🇪Munchen, Germany
Hospital de Gran Canaria Doctor Negrin
🇪🇸Las Palmas De Gran Canaria, Spain
St. James University Hospital
🇬🇧Leeds, United Kingdom
Klinikum der Universitat Regensburg
🇩🇪Regensburg, Germany
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Centrum Onkologii im. Marii Sklodowskiej-Curie
🇵🇱Warsaw, Poland
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
🇵🇹Lisboa, Portugal
UZ Leuven
🇧🇪Leuven, Belgium
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Montefiore Einstein Cancer Center
🇺🇸Bronx, New York, United States
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Mattel Children's Hospital UCLA
🇺🇸Los Angeles, California, United States
Blood & Marrow Transplant Center
🇺🇸Orlando, Florida, United States
University of California, San Francisco Medical Center
🇺🇸San Francisco, California, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
MUSC-Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
VA Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
University of Kansas Medical Center
🇺🇸Westwood, Kansas, United States