A Study of Maribavir Compared to Valganciclovir to Treat Cytomegalovirus Infections in People Who Have Received Stem Cell Transplants

Phase 3

Completed

Conditions: Cytomegalovirus (CMV)

Interventions: Drug: Maribavir
Drug: Valganciclovir
Other: Placebo

Registration Number: NCT02927067

Lead Sponsor: Shire

Brief Summary: This study is about treatment options for cytomegalovirus infections in people who have received stem cell transplants. The main aim of the study is to check if the cytomegalovirus infection can no longer be detected after treatment with marivabir or valganciclovir.

Participants will take 2 tablets of marivabir or valganciclovir and 2 tablets of placebo twice a day for 8 weeks. A placebo will look like marivabir or valganciclovir but will not have any medicine in it.

After treatment, each participant will be followed up for up to 12 weeks.

Participants will visit their study clinic up to 18 times during the study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 553

Inclusion Criteria

Be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participants before completing any study-related procedures. During the COVID-19 public health emergency, informed consent from a potential or current trial participant may, if permitted by local laws and regulations, be obtained via electronic informed consent (eIC) capabilities or an electronic face-to-face consent interview when these individuals are unable to travel to the site (FDA COVID-19 Guidance, 27 January 2021, Q11).
Be greater than or equal to (>=) 16 years of age at the time of consent.
Be a recipient of hematopoietic stem cell transplant.
Have a documented asymptomatic CMV infection, with a screening value of CMV DNA >=1365 International Units per millilitre (IU/mL) to less than or equal to (<=) 273000 IU/mL in whole blood or >=455 IU/mL to <=91000 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. Same laboratory and same sample type (whole blood or plasma) should be used for these assessments. Asymptomatic CMV infection is defined as an infection that does not present with tissue invasive CMV disease, as assessed by the investigator. Participants with CMV DNA less than (<) 910 and >=455 IU/mL in plasma or <2730 and >=1365 IU/mL in whole blood will also need to meet at least 1 of the following criteria for high-risk CMV infection to be eligible:
1. Human leukocyte antigen (HLA)-related (sibling) donor with at least 1 mismatch at 1 of the following 3 HLA-gene loci: HLA-A, -B or -DR,
2. Haploidentical donor
3. Unrelated donor with at least 1 mismatch at 1 of the following 4 HLA -gene loci: HLA-A, -B, -C and -DRB1,
4. Use of umbilical cord blood as stem cell source,
5. Use of ex vivo T-cell-depleted grafts,
6. Grade 2 or greater graft-versus-host-disease (GVHD), requiring the use of systemic corticosteroids (defined as the use of >=1 milligram per kilogram per day (mg/kg/day) of prednisone or equivalent dose of another corticosteroid).
Have the current CMV infection as the first episode of CMV viremia after HSCT, either primary or reactivation, which in the investigator's opinion requires treatment.
Per investigator's judgment, be eligible for treatment with valganciclovir.
Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
1. Absolute neutrophil count to >=1000 per cubic millimeter (/mm^3) [1.0*10^9/L].
2. Platelet count >=25,000/mm^3 [25*10^9/L].
3. Hemoglobin >=8 grams per deciliter (g/dL).
4. Estimated creatinine clearance >=30 milliliters per minute (mL/min).
Have a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Urine pregnancy tests may be done per institutional requirements; however they are not sufficient for eligibility determination. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward the last dose of study treatment.
Be able to swallow tablets.
Have life expectancy of >=8 weeks.
Weigh >=40 kilograms (kg).
Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.

Exclusion Criteria

Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
Have a CMV infection that is known to be genotypically resistant to ganciclovir, valganciclovir, foscarnet, or cidofovir based on documented evidence.
Be presenting with recurrent CMV infection (defined as a new detection of CMV infection in a participants who had at least one previously documented episode of CMV infection post-transplant, and who has had at least 2 weeks of undetectable CMV DNA between the episodes during active surveillance, based on same local laboratory and same sample type). The Participants must also have been off any anti-CMV treatment between the current and prior infection. Otherwise, the current infection may be considered continuation of the prior infection.
Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus [HSV] co-infection requiring use of any of these agents after the randomization) or would need a co-administration with maribavir for CMV infection.
Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated.

Note: Participants who may be receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Participants receiving letermovir must discontinue use 3 days prior to first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.

Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or letermovir) for the current CMV infection for longer than 72 hours.
Have known hypersensitivity to the active substance or to an excipient of the study treatments.
Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral medication.
Require mechanical ventilation or vasopressors for hemodynamic support at the time of randomization.
Be female and pregnant or nursing.
Have previously completed, discontinued, or have been withdrawn from this study.
Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or CMV vaccine at any time.
Have received any unapproved agent or device within 30 days before initiation of study treatment.
Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.
Have previously received maribavir.
Have serum aspartate aminotransferase (AST) greater than (>) 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >= 3.0*ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central laboratory.
Have known (previously documented) positive results for human immunodeficiency virus (HIV). Participants must have a confirmed negative HIV test result within 3 months of study entry or, if unavailable, be tested by a local laboratory during the screening period.
Have active malignancy with the exception of nonmelanoma skin cancer, as determined by the investigator. Participants who experience relapse or progression of their underlying malignancy (for which HSCT was performed), as determined by the investigator, are not to be enrolled.
Be undergoing treatment for acute or chronic hepatitis C

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Maribavir 400 mg BID	Maribavir	Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.
Maribavir 400 mg BID	Placebo	Participants received 400 mg of maribavir along with a placebo matched to valganciclovir, BID orally for 8 weeks.
Valganciclovir 900 mg BID	Valganciclovir	Participants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.
Valganciclovir 900 mg BID	Placebo	Participants received 900 milligrams (mg) of valganciclovir along with a placebo matched to maribavir, twice daily (BID) orally for 8 weeks. Valganciclovir dose was allowed to be adjusted to 450 mg BID or 450 mg QD based on renal function impairment assessed at baseline or development of neutropenia during the study.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribose Nucleic Acid (DNA) at the End of Study Week 8	Week 8	Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. \<137 International units per milliliter \[IU/mL\]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for the primary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Confirmed Recurrence of Viremia During First 8 Weeks of the Study	Up to Week 8	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) lower limit of quantification (LLOQ, i.e. \>=137 International units per milliliter \[IU/mL\]) when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ, i.e. \<137 IU/mL) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
Area Under the Concentration-Time Curve Over the 12-Hour Dosing Interval at Steady State AUC(0-tau) of Maribavir for Adolescent Participants Only	Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants Only	Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants Only	Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Number of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at Week 8 After Receiving 8 Weeks of Study Assigned Treatment	Week 8	Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. \<137 International units per milliliter \[IU/mL\]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this secondary endpoint, the participant must have received exclusively study-assigned treatment for 8 weeks. Participants who discontinued treatment early were non-responders for this endpoint.
Number of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20	Week 8 through Weeks 12, 16 and 20	Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. \<137 International units per milliliter \[IU/mL\]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this secondary endpoint, the participant must have received exclusively study-assigned treatment for 8 weeks.
Number of Participants With Confirmed Recurrence of Viremia During the Follow-up Period	From Week 9 up to Week 20	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
Number of Participants With Grade 3 or 4 (Shift From Baseline Grade <3) and Grade 4 Neutropenia (Shift From Baseline Grade <4) While on Study Treatment	From start of study drug to end of study drug + 1 day (up to approximately Week 8)	Grade 3 and grade 4 neutropenia are defined as absolute neutrophil count (ANC) \<1000 per cubic millimeter (/mm\^3) and ANC \<500/mm\^3 respectively. Incidence of Grade 3 or 4 neutropenia represents the percentage of participants with Grade \<3 (or missing) neutropenia at baseline, but Grade 3 or 4 while on study treatment. Incidence of Grade 4 neutropenia represents the number of participants with Grade \<4 (or missing) neutropenia at baseline, but Grade 4 while on study treatment.
Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants Only	Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1
Number of Participants Who Maintained Confirmed CMV Viremia Clearance at Week 8 After Receiving Study-Assigned Treatment Through Study Weeks 12 and 20 Regardless of Whether Study Assigned Treatment Was Completed	Week 8 through Weeks 12 and 20	Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. \<137 International units per milliliter \[IU/mL\]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this secondary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether the 8-week study-assigned treatment was completed or discontinued early) and had no symptoms of tissue invasive CMV disease at Week 8, Week 8 through Week 12, and Week 8 through Week 20, respectively.
Number of Participants With Confirmed Recurrence of Viremia at Any Time During the Study	Up to Week 20	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
Number of Participants With Confirmed Recurrence of Viremia While on Study Treatment and Off Treatment	Baseline up to Week 20	Recurrence of CMV viremia is defined as plasma CMV DNA concentration greater than or equal to (\>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive plasma samples at least 5 days apart, after being unquantifiable (\<LLOQ) for at least 5 days in 2 consecutive samples during the first 8 weeks of the study, during the 12 weeks of the follow up study phase, and at any time during the study.
Number of Participants With Treatment-Emergent Adverse Events During the On-Treatment Period	From the start of the study treatment to 7 days after the last dose of study treatment (up to approximately Week 9)	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE that has a start date on or after the first dose of study treatment, or that has a start date before the date of first dose of study treatment but increases in severity after the first dose of study treatment, will be considered a treatment-emergent AE (TEAE).
Number of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at the End of Week 8, Followed by Maintenance of Treatment Effect at Week 16	Week 8 up to Week 16	Confirmed CMV viremia clearance is defined as plasma CMV DNA concentrations less than lower limit of quantification (LLOQ; i.e. \<137 International units per milliliter \[IU/mL\]), when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive post baseline samples separated by at least 5 days. To be considered a responder for this key secondary endpoint, the participant must have received exclusively study-assigned treatment (regardless of whether study-assigned treatment was completed). CMV Infection Symptom Control is defined as no new clinical findings of CMV tissue invasive disease. Maintenance of Treatment Effect is defined as maintaining confirmed CMV viremia clearance and CMV infection symptom control through Week 16.
Predose Concentration (Cmin) of Maribavir	Weeks 1, 4, and 8: pre-morning dose	The primary plasma maribavir concentration dataset (primary concentration dataset) includes all plasma maribavir concentrations. Missing PK sampling times are imputed according to the sparse sampling schedule in primary concentration dataset.
Maximum Observed Plasma Concentration (Cmax) of Maribavir for Adolescent Participants Only	Pre-morning dose, 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose of Week 1

Trial Locations

Locations (129): UCLA Medical Center
🇺🇸
Los Angeles, California, United States
UMass Memorial Medical Center
🇺🇸
Worcester, Massachusetts, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
Medizinische Universitat Wien (Medical University of Vienna)
🇦🇹
Vienna, Wien, Austria
UZ Antwerpen
🇧🇪
Edegem, Antwerpen, Belgium
Elisabethinen Hospital Linz
🇦🇹
Linz, Austria
Institute Jules Bordet
🇧🇪
Bruxelles, Brussels, Belgium
Universitair Ziekenhuis Brussel - PIN
🇧🇪
Jette, Brussels, Belgium
University Hospital Gent
🇧🇪
Gent, Oost-Vlaanderen, Belgium
UZ Leuven
🇧🇪
Leuven, Vlaams Brabant, Belgium
AZ Sint-Jan AV
🇧🇪
Brugge, West-Vlaanderen, Belgium
CHU de Liège
🇧🇪
Liège, Belgium
Queen Elizabeth II Health Sciences Center
🇨🇦
Halifax, Nova Scotia, Canada
Peking University First Hospital
🇨🇳
Beijing, Beijing, China
Vancouver General Hospital
🇨🇦
Vancouver, British Columbia, Canada
Hamilton Health Sciences Corporation
🇨🇦
Hamilton, Ontario, Canada
Peking University People's Hospital
🇨🇳
Beijing, Beijing, China
Xiangya Hospital Central South University
🇨🇳
Changsha, China
Henan Cancer Hospital
🇨🇳
Zhengzhou, China
Guangzhou First People's Hospital
🇨🇳
Guangzhou, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳
Hangzhou Zhejiang, China
University Hospital Center Zagreb
🇭🇷
Zagreb, Croatia
Institut de Cancérologie Strasbourg Europe
🇫🇷
Strasbourg Cedex, Bas-Rhin, France
Fakultni nemocnice v Motole
🇨🇿
Prague, Praha, Hlavní Mesto, Czechia
Hopital de Hautepierre
🇫🇷
Strasbourg Cedex, Bas-Rhin, France
Ustav hematologie a krevni transfuze
🇨🇿
Praha, Czechia
CHU de Bordeaux
🇫🇷
Pessac, Gironde, France
CHU de GRENOBLE
🇫🇷
GRENOBLE Cedex 9, Isère, France
Hôpital Universitaire Dupuytren
🇫🇷
Limoges, Haute-Vienne, France
Hôtel Dieu
🇫🇷
Nantes, Loire-Atlantique, France
Hopital Henri Mondor
🇫🇷
Créteil, Val-de-Marne, France
Hôpital Saint Antoine
🇫🇷
Paris, France
Institut Paoli Calmettes
🇫🇷
Nice, France
Hôpital Saint Louis
🇫🇷
Paris, France
EDOG - Institut Claudius Regaud - PPDS
🇫🇷
Toulouse cedex 9, France
Universitätsklinikum Münster
🇩🇪
Muenster, Nordrhein-Westfalen, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪
Mainz, Rheinland-Pfalz, Germany
Emory University
🇺🇸
Atlanta, Georgia, United States
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
Universitätsklinik Rostock
🇩🇪
Rostock, Germany
Universitätsklinikum Augsburg
🇩🇪
Augsburg, Germany
Martin Luther Universitat Halle Wittenberg
🇩🇪
Halle, Germany
Universitätsklinikum Hamburg Eppendorf
🇩🇪
Hamburg, Germany
Attikon University General Hospital
🇬🇷
Athina, Attiki, Greece
Robert Bosch Krankenhaus
🇩🇪
Stuttgart, Germany
Georgios Papanikolaou General Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
🇭🇺
Budapest, Hungary
Sheba Medical Center - PPDS
🇮🇱
Ramat Gan, HaMerkaz, Israel
Hadassah Medical Center - PPDS
🇮🇱
Jerusalem, Yerushalayim, Israel
Rambam Medical Center - PPDS
🇮🇱
Haifa, Israel
Tel Aviv Sourasky Medical Center PPDS
🇮🇱
Tel-Aviv, Israel
Ospedale Dell'Angelo
🇮🇹
Brescia, Lombardia, Italy
Ospedale Infantile Regina Margherita - INCIPIT - PIN
🇮🇹
Torino, Piemonte, Italy
Azienda Ospedaliera Universitaria Integrata Di Verona
🇮🇹
Verona, Veneto, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹
Firenze, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
Fondazione Policlinico Universitario A Gemelli
🇮🇹
Roma, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹
Torino, Italy
Dong-A University Hospital
🇰🇷
Busan, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷
Daegu, Korea, Republic of
Auckland City Hospital
🇳🇿
Grafton, Auckland, New Zealand
Canterbury Health Laboratories
🇳🇿
Christchurch, South Island, New Zealand
Regional Oncology Center
🇷🇺
Irkutsk, Russian Federation
First St. Petersburg State Medical University n.a. I.P Pavlov
🇷🇺
Saint Petersburg, Sankt-Peterburg, Russian Federation
Kirov Research Institute of Haematology and Blood Transfusion
🇷🇺
Kirov, Russian Federation
National University Hospital
🇸🇬
Singapore, Singapore
Singapore General Hospital (SGH)
🇸🇬
Singapore, Singapore
Hospital Universitario Germans Trias i Pujol
🇪🇸
Badalona, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸
Santander, Cantabria, Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico
🇪🇸
Salamanca, Castilla Y León, Spain
Hospital Universitario Vall d'Hebrón - PPDS
🇪🇸
Barcelona, Spain
Hospital Universitario Virgen de Las Nieves
🇪🇸
Granada, Spain
C.H. Regional Reina Sofia - PPDS
🇪🇸
Cordoba, Spain
ICO l'Hospitalet Hospital Duran i Reynals
🇪🇸
Barcelona, Spain
Hospital Universitario de La Princesa
🇪🇸
Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸
Madrid, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸
Madrid, Spain
Hospital Universitario de Donostia
🇪🇸
San Sebastian Gipuzkoa, Spain
Hospital Clinico Universitario de Valencia
🇪🇸
Valencia, Spain
Universitätsspital Zürich
🇨🇭
Zurich, Switzerland
Ankara University Medica Faculty Hematology Department Clinical Research Area PPDS
🇹🇷
Ankara, Turkey
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
Baskent University Medical Faculty Adana Practice and Research Center
🇹🇷
Adana, Turkey
Birmingham Heartlands Hospital
🇬🇧
West Midlands, Birmingham, United Kingdom
Hammersmith Hospital
🇬🇧
London, London, City Of, United Kingdom
St George's Hospital
🇬🇧
Tooting, London, United Kingdom
The Christie NHS Foundation Trust - PPDS
🇬🇧
Manchester, United Kingdom
Southampton University Hospitals NHS Trust
🇬🇧
Southampton, United Kingdom
Brigham and Womens Hospital
🇺🇸
Boston, Massachusetts, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
VA Puget Sound Health Care System - NAVREF - PPDS
🇺🇸
Seattle, Washington, United States
The First Affiliated Hospital of Soochow University
🇨🇳
Suzhou, Jiangsu, China
University of Chicago
🇺🇸
Chicago, Illinois, United States
Stanford University
🇺🇸
Stanford, California, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Joan and sandford I. Weill Medical College of Cornell University Clinic
🇺🇸
New York, New York, United States
Hopital Jean Minjoz
🇫🇷
Besnçon, France
CHU Angers
🇫🇷
Angers Cedex 9, Maine-et-Loire, France
Universität des Saarlandes
🇩🇪
Homburg, Saarland, Germany
University College London
🇬🇧
London, London, City Of, United Kingdom
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Colorado Blood Cancer Institute - PPDS
🇺🇸
Denver, Colorado, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
TriStar Centennial Medical Center
🇺🇸
Nashville, Tennessee, United States
Texas Transplant Institute
🇺🇸
San Antonio, Texas, United States
Harper University Hospital
🇺🇸
Detroit, Michigan, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Clatterbridge Cancer Centre Liverpool
🇬🇧
Liverpool, Merseyside, United Kingdom
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Maryland School of Medicine
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
MTZ Clinical Research Sp z o o - PRATIA - PPDS
🇵🇱
Warszawa, Mazowieckie, Poland
Universitatsklinikum Leipzig
🇩🇪
Leipzig, Sachsen, Germany
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱
Wroclaw, Dolnoslaskie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Brussels, Belgium
Helios Klinikum Berlin-Buch
🇩🇪
Berlin, Germany
Universitätsklinikum Tübingen
🇩🇪
Tübingen, Germany
Hospital Regional Universitario de Malaga - Hospital General
🇪🇸
Málaga, Spain
Mayo Clinic - PIN
🇺🇸
Rochester, Minnesota, United States
The Medical College of Wisconsin, Inc.
🇺🇸
Milwaukee, Wisconsin, United States
Saint Davids South Austin Medical Center
🇺🇸
Austin, Texas, United States
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
Nanfang Hospital Southern Medical University
🇨🇳
Guangzhou, Guangdong, China