Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir

Phase 3

Completed

Conditions: Cytomegalovirus (CMV)

Interventions: Drug: Maribavir
Drug: Ganciclovir
Drug: Valganciclovir
Drug: Foscarnet
Drug: Cidofovir

Registration Number: NCT02931539

Lead Sponsor: Shire

Brief Summary: The purpose of this study is to compare the efficacy of maribavir to investigator-assigned anti-Cytomegalovirus (CMV) therapy in CMV viremia clearance in transplant recipients who are refractory or resistant to prior anti-CMV treatment.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 352

Inclusion Criteria

The participant must 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 participant before completing any study-related procedures.
The participant must be a recipient of hematopoietic stem cell or solid organ transplant.
The participant must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 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. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
The participant must have a current CMV infection that is refractory to the most recently administered of the four anti-CMV treatment agents. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir.

a. Participants with documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, foscarnet, and/or cidofovir must also meet the definition of refractory CMV infection.
The Investigator must be willing to treat the participant with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.
The participant must be >= 12 years of age at the time of consent.
The participant must weigh >= 35 kilogram (kg).
The participant must 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 (ANC) >= 1000/ millimeter cube (mm^3) (1.0 x 10^9/liter [L])
2. Platelet count >= 25,000/mm^3 [25 x 10^9/L],
3. Hemoglobin >= 8 grams per deciliter (g/dL).
4. Estimated glomerular filtration rate (eGFR) > 30 (milliliters per minute (mL/min) /1.73 square meter (m^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for participants >= 18 years of age or Schwartz formula for participants less than (<) 18 years of age.
The participant must have a negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Additional urine pregnancy tests may be done per institutional requirements. 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 if treated with maribavir, ganciclovir, valganciclovir, or cidofovir and for 180 days afterward if treated with foscarnet.
The participant must be able to swallow tablets, or receive tablets crushed and/or dispensed in water via nasogastric or orogastric tube.
The participant must be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
The participant must be willing to provide necessary samples (example [e.g,] biopsy) for the diagnosis of tissue invasive CMV disease at baseline as determined by the Investigator.
The participant must have a life expectancy of >= 8 weeks.

Exclusion Criteria

Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator.
Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A participant who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If participant is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the participant must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.
Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Participants 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 at least 3 days prior to the first dose of study treatment. Participants receiving artesunate must discontinue the use prior to the first dose of study treatment.
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/enteral medication.
Have known hypersensitivity to the active substance or to an excipient for a study treatment.
Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis).
Have serum aspartate aminotransferase (AST) > 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) > 5 times ULN at screening, or total bilirubin >= 3.0 x ULN at screening (except for documented Gilbert's syndrome), by local or central lab. Participants with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT > 5 times ULN at screening.
Have known 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.
Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
Be female and pregnant or breast feeding.
Have previously received maribavir.
Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or investigational CMV vaccine at any time.
Have received any unapproved agent or device within 30 days before initiation of study treatment.
Have active malignancy with the exception of nonmelanoma skin cancer. Participants who have had a hematopoietic stem cell transplant (HSCT) and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled.
Be undergoing treatment for acute or chronic hepatitis C.
Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the participant.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Maribavir Treatment	Maribavir	Participants will receive 400 milligrams (mg) (2x200 mg tablets) maribavir twice daily orally (doses separated by a minimum of 8 hours) for 8 weeks.
Investigator-Assigned Treatment	Ganciclovir	Participants will receive anti-CMV agent best suited to treat the respective participant as per the investigator's prescribed dosing regimen for 8 weeks. Agents of choice include: ganciclovir, valganciclovir, foscarnet, or cidofovir.
Investigator-Assigned Treatment	Cidofovir	Participants will receive anti-CMV agent best suited to treat the respective participant as per the investigator's prescribed dosing regimen for 8 weeks. Agents of choice include: ganciclovir, valganciclovir, foscarnet, or cidofovir.
Investigator-Assigned Treatment	Valganciclovir	Participants will receive anti-CMV agent best suited to treat the respective participant as per the investigator's prescribed dosing regimen for 8 weeks. Agents of choice include: ganciclovir, valganciclovir, foscarnet, or cidofovir.
Investigator-Assigned Treatment	Foscarnet	Participants will receive anti-CMV agent best suited to treat the respective participant as per the investigator's prescribed dosing regimen for 8 weeks. Agents of choice include: ganciclovir, valganciclovir, foscarnet, or cidofovir.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8	Week 8	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration less than (\<) lower limit of quantification (LLOQ) that is, \<137 International Units per milliliter (IU/mL) when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants with confirmed CMV viremia clearance at end of study Week 8 regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy, and could not have received alternative anti-CMV treatment were reported.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment	At Week 8 through Weeks 12, 16 and 20	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants who achieved confirmed CMV viremia clearance after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20	At Week 8 through Weeks 12, 16 and 20	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved confirmed CMV viremia clearance and CMV infection control after receiving 8 weeks study-assigned treatment at end of Week 8, and maintained this effect through 12, 16 and 20 were reported.
Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	At Week 8 through Weeks 12 and 20	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who maintained CMV viremia clearance and CMV infection symptom control at the end of study Week 8 through Weeks 12 and 20 regardless of whether either study-assigned treatment was discontinued before 8 weeks of therapy were reported.
Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks of Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	At Week 8	Recurrence of CMV viremia was 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 achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the first 8 weeks of study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.
Percentage of Participants With Recurrence of CMV Viremia During the 12 Weeks Follow-up Period Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	End of Week 8 up to Week 20 (12 weeks follow-up period)	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the 12 weeks follow-up period regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.
Percentage of Participants With Recurrence of CMV Viremia at Any Time on Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy	Baseline up to Week 20	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during at any time on study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported.
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at End of Week 8, Followed by Maintenance of Treatment Effect at Week 16	Up to Week 16	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants who achieved CMV viremia clearance and CMV infection symptom control at end of Week 8 through Week 16 were reported.
Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose	Apparent volume of distribution (Vz/F) of maribavir for adolescent participants was planned to be reported.
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment	Baseline up to Week 8	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia during the first 8 Weeks of the treatment who completed 8 weeks of study-assigned treatment were reported.
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period	End of Week 8 up to Week 20 (12 weeks follow-up period)	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 12 weeks of follow-up period were reported.
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study	Baseline up to Week 20	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 20 weeks of study were reported.
Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment	Baseline up to termination of study treatment (up to Week 8)	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia while on study-assigned treatment period were reported.
Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period	Termination of study treatment (Week 8) up to the End of the Study (Week 20)	Recurrence of CMV viremia was defined as plasma CMV DNA concentration \>=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia while off study-assigned treatment during follow-up period were reported.
Number of Participants Who Had Maribavir CMV Resistance at Baseline	At Baseline	Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had maribavir CMV resistance at baseline were reported.
Number of Participants Who Had Post-baseline Resistance to Maribavir	After first dose of study drug up to Week 20	Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had post-baseline resistance to maribavir were reported.
Number of Participants With All-cause Mortality by the End of the Study	From enrollment up to end of study (approximately 44 months)	All-cause mortality was analyzed by the end of study regardless of the use of rescue treatment or alternative anti-CMV treatment. Number of participants who died during the entire study period were reported.
Time to All Cause Mortality	From enrollment to last serious adverse event (SAE) follow-up (approximately Week 28)	The time to all-cause mortality by the end of the study participation in days was calculated. Participants who were alive at the last study follow-up (regardless of use of rescue or alternative anti-CMV treatment), withdrew from study or were lost to follow-up were censored at the date of last contact.
Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment	From start of maribavir rescue treatment through 8 weeks	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days, regardless of whether the rescue treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants who achieved confirmed CMV viremia clearance at end of Week 8 after starting maribavir rescue treatment were reported.
Percentage of Participants Receiving Maribavir Rescue Treatment Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 With Maintenance of Effect Through Week 16	Up to Week 16	Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration \<LLOQ that is, \<137 IU/mL when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive postbaseline samples, separated by at least 5 days. CMV infection symptom control was defined as resolution or improvement of tissue invasive CMV disease or CMV syndrome for participants symptomatic at baseline, or maintaining no symptoms of tissue invasive CMV disease or CMV syndrome for participants asymptomatic at baseline. Percentage of participants receiving maribavir rescue treatment who achieved confirmed CMV viremia clearance and CMV infection symptom control at Week 8 with maintenance of effect through Week 16 were reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period	Baseline up to 7 days or 21 days (if cidofovir used) after the last dose of study treatment (up to Week 8)	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study-assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment.
Predose Concentration (Cmin) of Maribavir	Predose at Week 1, 4 and 8	Cmin of maribavir was reported.
Area Under the Concentration Time Curve Over the 12-hour Dosing Interval at Steady State (AUC0-tau) of Marivabir for Adolescent Participants	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose, Week 4: Pre-morning dose, and Week 8: Pre-morning dose and 2-4 hour post morning dose	AUC0-tau of maribavir for adolescent participants was planned to be reported.
Maximum Plasma Concentration (Cmax) of Maribavir for Adolescent Participants	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose	Cmax of maribavir for adolescent participants was planned to be reported.
Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose	Tmax of maribavir for adolescent participants was planned to be reported.
Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants	Week 1: Pre-morning dose and 1, 2, 3, 4, 6, 8 and 12 hours post morning dose	Apparent oral clearance (CL/F) of maribavir for adolescent participants was planned to be reported.

Trial Locations

Locations (132): University of Maryland
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
University of Southern California
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Los Angeles, California, United States
UCLA Medical Center
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Los Angeles, California, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Feinberg School of Medicine Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸
Maywood, Illinois, United States
William Beaumont Hospital
🇺🇸
Royal Oak, Michigan, United States
SUNY Upstate Medical Center
🇺🇸
Syracuse, New York, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
Emory University Hospital
🇺🇸
Atlanta, Georgia, United States
Stanford University
🇺🇸
Stanford, California, United States
University of Texas Southwestern Medical Center
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Dallas, Texas, United States
Centre Hospitalier Lyon Sud
🇫🇷
Pierre-bénite, Rhône, France
Azienda Ospedaliero Universitaria Pisana
🇮🇹
Pisa, Italy
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
Universitätsklinikum Erlangen
🇩🇪
Erlangen, Germany
The Alfred Hospital
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Melbourne, Victoria, Australia
Hackensack University Medical Center
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Hackensack, New Jersey, United States
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
🇮🇹
Ancona, Marche, Italy
CHRU de Poitiers La Miletrie
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Poitiers, France
CHU Dupuytren
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Limoges Cedex, France
Hôpital Paul Brousse
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Villejuif, Val-de-Marne, France
CHU Amiens Hôpital Sud
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Amiens, France
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
University Clinic Heidelberg - PPDS
🇩🇪
Heidelberg, Germany
Churchill Hospital
🇬🇧
Oxford, United Kingdom
University Hospital Center Zagreb
🇭🇷
Zagreb, Croatia
Fondazione Policlinico Universitario A Gemelli
🇮🇹
Roma, Italy
CHRU Bretonneau
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Tours, Indre-et-Loire, France
Hopital Gabriel Montpied
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Clermont-Ferrand, France
CHRU Rennes
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Rennes, Ille-et-Vilaine, France
UZ Gent
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Gent, Oost-Vlaanderen, Belgium
AZ Sint-Jan AV
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Brugge, West-Vlaanderen, Belgium
Ospedale San Raffaele S.r.l. - PPDS
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Milano, Lombardia, Italy
Royal Melbourne Hospital
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Parkville, Victoria, Australia
LMU Klinikum der Universität München
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München, Germany
Hôpital Saint Louis
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Paris, France
Sir Charles Gairdner Hospital
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Nedlands, Washington, Australia
Hospital Universitario Germans Trias i Pujol
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Badalona, Barcelona, Spain
Centre Hospitalier Universitaire Vaudois
🇨🇭
Lausanne, Vaud (fr), Switzerland
Azienda Ospedaliero Universitaria di Parma
🇮🇹
Parma, Italy
Universitätsklinikum Essen
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Essen, Nordrhein-Westfalen, Germany
CHU de GRENOBLE
🇫🇷
Grenoble, France
Fundacio Puigvert
🇪🇸
Barcelona, Spain
Istituto Europeo Di Oncologia
🇮🇹
Milano, Lombardia, Italy
Royal Liverpool and Broadgreen University Hospitals NHS Trust
🇬🇧
Liverpool, United Kingdom
Universitätsklinikum Tübingen
🇩🇪
Tübingen, Germany
Hospital Universitario de Cruces
🇪🇸
Barakaldo, Spain
Manchester Royal Infirmary - PPDS
🇬🇧
Manchester, United Kingdom
Singapore General Hospital (SGH)
🇸🇬
Singapore, Singapore
Hospital Clinico Universitario de Valencia
🇪🇸
Valencia, Spain
Sheffield Childrens Hospital
🇬🇧
Sheffield, Yorkshire, United Kingdom
Hospital de La Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Royal Free Hospital
🇬🇧
London, United Kingdom
Imperial College Healthcare NHS Trust
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London, London, City Of, United Kingdom
Hospital Universitario de Bellvitge
🇪🇸
L'Hospitalet de Llobregat, Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico
🇪🇸
Salamanca, Spain
Wythenshawe Hospital - PPDS
🇬🇧
Wythenshawe, Manchester, United Kingdom
Ochsner Clinic Foundation
🇺🇸
New Orleans, Louisiana, United States
Azienda Sanitaria Universitaria Integrata di Udine
🇮🇹
Udine, Italy
CHRU Lille
🇫🇷
Lille Cedex, France
Groupement Hospitalier Edouard Herriot
🇫🇷
Lyon, France
Groupe Hospitalier Necker Enfants Malades
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Paris, France
Institut de Cancerologie de la Loire
🇫🇷
Saint-Priest en Jarez, France
Hopital de Hautepierre
🇫🇷
Strasbourg, France
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
🇬🇧
London, United Kingdom
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪
Mainz, Rheinland-Pfalz, Germany
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
UC Davis Medical Center
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Sacramento, California, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
The Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
Henry Ford Health System
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Detroit, Michigan, United States
University of Minnesota
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Minneapolis, Minnesota, United States
Mayo Clinic - PPDS
🇺🇸
Rochester, Minnesota, United States
Duke University Medical Center
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Durham, North Carolina, United States
University of Nebraska Medical Center
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Omaha, Nebraska, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
University of Utah Health Sciences Center - PPDS
🇺🇸
Salt Lake City, Utah, United States
Cincinnati Children's Hospital Medical Center - PIN
🇺🇸
Cincinnati, Ohio, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Brigham and Womens Hospital
🇺🇸
Boston, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸
Worcester, Massachusetts, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
New York Presbyterian Hospital - Weill-Cornell
🇺🇸
New York, New York, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Medical University of South Carolina - PPDS
🇺🇸
Charleston, South Carolina, United States
St Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
Baylor All Saints Medical Center
🇺🇸
Fort Worth, Texas, United States
Monash Health, Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
Princess Alexandra Hospital
🇦🇺
Brisbane, Australia
Tiroler Landeskrankenanstalten GmbH
🇦🇹
Innsbruck, Austria
Allgemeines Krankenhaus der Stadt Wien
🇦🇹
Wien, Austria
UZ Antwerpen
🇧🇪
Edegem, Antwerpen, Belgium
Institut Jules Bordet
🇧🇪
Bruxelles, Brussels, Belgium
UZ Leuven
🇧🇪
Leuven, Vlaams Brabant, Belgium
ZNA Stuivenberg
🇧🇪
Antwerpen, Belgium
UZ Brussel
🇧🇪
Brussels, Belgium
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
University of Alberta
🇨🇦
Edmonton, Alberta, Canada
Hôpital Erasme
🇧🇪
Bruxelles, Belgium
Hamilton Health Sciences Corporation
🇨🇦
Hamilton, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
McGill University Health Center
🇨🇦
Montreal, Quebec, Canada
Copenhagen University Hospital
🇩🇰
København Ø, Capital, Denmark
Hôpital Saint Antoine
🇫🇷
Paris, France
Hôpital Civil
🇫🇷
STRASBOURG Cedex, France
Universitatsklinikum Leipzig
🇩🇪
Leipzig, Sachsen, Germany
Hospital Universitario Vall d'Hebrón - PPDS
🇪🇸
Barcelona, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸
Madrid, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
Birmingham Heartlands Hospital
🇬🇧
West Midlands, Birmingham, United Kingdom
Beatson West of Scotland Cancer Centre - PPDS
🇬🇧
Glasgow, Glasgow City, United Kingdom
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
AdventHealth
🇺🇸
Orlando, Florida, United States
Hopital Foch
🇫🇷
Suresnes, Hauts-de-Seine, France
University Hospital Coventry
🇬🇧
Coventry, Birmingham, United Kingdom
CHRU Brest - Hospital Cavale Blanche
🇫🇷
Brest, Finistère, France
University Health Network
🇨🇦
Toronto, Ontario, Canada
University Hospitals Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
Hôpital de Rangueil
🇫🇷
Toulouse, Haute-Garonne, France
CHRU Nantes
🇫🇷
Nantes, Loire-Atlantique, France
Hôpital de La Croix Rousse
🇫🇷
Lyon, Rhône, France
Hopital Henri Mondor
🇫🇷
Créteil, Val-de-Marne, France
St. Joseph's Healthcare Hamilton
🇨🇦
Hamilton, Ontario, Canada