A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant
- Conditions
- Multiple MyelomaAutologous Stem Cell Transplant
- Interventions
- Drug: PlaceboDrug: Ixazomib Citrate
- Registration Number
- NCT02181413
- Lead Sponsor
- Takeda
- Brief Summary
The purpose of this study is to determine the effect of ixazomib citrate maintenance therapy on progression-free survival (PFS), compared to placebo, in participants with newly diagnosed multiple myeloma (NDMM) who have had a response (complete response \[CR\], very good partial response \[VGPR\], or partial response \[PR\]) to induction therapy followed by high-dose therapy (HDT) and autologous stem cell transplant (ASCT).
- Detailed Description
The investigational drug being tested in this study is called ixazomib citrate. Ixazomib citrate is being tested to slow disease progression and improve overall survival in people who have NDMM and who have had any type of positive response to induction therapy followed by HDT and ASCT. This study will look at the effect ixazomib citrate has on the length of time that participants are free of progressive disease (PD) and their overall survival (OS).
The study enrolled 656 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need, or if the disease has progressed and the information is required for planning the next treatment):
* Ixazomib citrate 3 mg for the first 4 cycles, then 4 mg for the remaining 22 cycles
* Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient.
All participants will be asked to take one capsule on Days 1, 8 and 15 of each 28-day cycle, for up to 26 cycles (approximately 24 months).
This multi-center trial will be conducted globally. The overall time to participate in this study is up to 107 months. Participants will make 28 visits to the clinic during the treatment period and will continue to make visits after treatment has ended. During this initial follow up period, participants will be assessed for disease status with follow up every 12 weeks. After the next line of therapy begins, follow-up will occur every 12 weeks until death or termination of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 656
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Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria.
-
Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.
-
Underwent standard of care (SOC) induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial.
-
Started screening no earlier than 75 days after transplant, completed screening within 15 days, and randomized no later than 115 days after transplant.
-
Must have not received post-ASCT consolidation therapy.
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Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.
-
ECOG performance status of 0 to 2.
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Female participants who:
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, AND
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, AND
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
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Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
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Suitable venous access for the study-required blood sampling.
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Is willing and able to adhere to the study visit schedule and other protocol requirements.
-
Must meet the following clinical laboratory criteria at study entry:
- Absolute neutrophil count (ANC) ≥ 1,000 per cubic milliliter (/mm^3) and platelet count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.
- Total bilirubin ≤ 1.5 * the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 * ULN.
- Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min).
- Multiple myeloma that has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy.
- Double (tandem) ASCT.
- Radiotherapy within 14 days before the first dose of study drug.
- Diagnosed or treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
- Major surgery within 14 days before randomization.
- Central nervous system involvement.
- Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
- Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
- Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study.
- Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
- Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
- Psychiatric illness/social situation that would limit compliance with study requirements.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
- Treatment with any investigational products within 60 days before the first dose of the study drug regimen.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Ixazomib citrate placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 26 until PD, unacceptable toxicity, or discontinuation for alternate reasons. Ixazomib Citrate Ixazomib Citrate Ixazomib citrate 3 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib citrate 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 until PD, unacceptable toxicity, or discontinuation for alternate reasons. Participants who have had any dose reductions due to adverse events (AEs) would not be dose escalated.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks (up to 45 months) PFS was defined as the time from the date of randomization to the date of first documentation of PD, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurred first. PD was defined as ≥25% increase from lowest value in: serum/urine M component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels must be \>10 milligrams per deciliter (mg/dL); participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must have been ≥10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size increase; hypercalcemia development.
- Secondary Outcome Measures
Name Time Method Time to Progression (TTP) Randomization up to PD (up to 107 months) TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria. PD is defined as ≥25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be \>10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be ≥10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development. Participants without documentation of PD at the time of analysis were censored at the date of last response assessment that is stable disease or better.
Overall Survival (OS) Randomization up to end of follow up period (up to 107 months) OS was measured as the time from the date of randomization to the date of death.
Percentage of Participants With Any Best Response Category Before PD or Subsequent Therapy Randomization up to EOT (up to 24 months) and thereafter every 4 weeks until initiation of the next line of therapy (up to 107 months) Response was assessed according to IMWG criteria. Best response includes partial response (PR), very good partial response (VGPR) and complete response (CR). PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to less than (\<)200 milligrams (mg) per 24 hours. VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours. CR is negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and \<5% plasma cells in bone marrow. Stringent CR (sCR) is CR and normal FLC ratio and absence of clonal plasma cells (PCs) by immunohistochemistry or 2- to 4-color flow cytometry. The decimal values of percentages were subjected to rounding off.
Second Progression Free Survival (PFS2) Randomization up to EOT (24 months); thereafter followed up every 4 weeks until initiation of next-line therapy and then every 12 weeks until second progressive disease (PD2) or death (up to 107 months) PFS2 is defined as the time from the date of randomization to the date of objective disease progression on next line treatment or death from any cause (whichever occurs first). PD is defined as ≥25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be \>10 mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be ≥10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.
Time to Start of the Next Line of Therapy Randomization up to 107 months Time to start of the next line of therapy was defined as the time from the date of randomization to the date of initiation dose of the next line of antineoplastic therapy following study treatment or death due to any cause, whichever occurred first. Participants who never took antineoplastic therapy were censored at the date of last contact or death.
Time to End of the Next Line of Therapy Randomization up to 107 months Time to end of the next line of therapy was defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment or death due to any cause, whichever occurred first or date of last contact for participants who never took antineoplastic therapy.
Duration of the Next Line of Therapy Up to 107 months Duration of the next line of therapy was defined as the time from the date of the first dose of the next line of therapy to the date of the last dose of the next antineoplastic therapy following study treatment or death due to any cause, whichever occurred first. Duration of the next line of therapy was analyzed on those participants who received the next line of therapy following the study treatment and duration was summarized using Kaplan-Meier method.
Percentage of Participants Who Develop a New Primary Malignancy Up to 107 months The decimal values of percentages were subjected to rounding off.
Number of Participants With Conversion to Minimal Residual Disease (MRD) Negative Baseline up to EOT (up to 24 months) MRD negativity (MRD-) is defined as absence of MRD and MRD positivity (MRD+) is defined as presence of MRD. The conversion rate from MRD positive to MRD negative was assessed and reported. Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry and a sequencing methodology.
Number of Participants With Maintenance of MRD Negativity Up to EOT (up to 24 months) MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. The maintenance of MRD negativity up to the end of treatment was assessed and reported in participants converting from MRD+ at Baseline to MRD negative. Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry and a sequencing methodology.
Correlation Between MRD Status and Progression Free Survival (PFS) From randomization up to 107 months PFS is defined as the time from the date of randomization to the date of first documentation of PD as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurred first, assessed for up to 107 months in this outcome measure.
Correlation Between MRD Status and Overall Survival (OS) From randomization up to 107 months OS was measured as the time from the date of randomization to the date of death, assessed for up to 107 months in this outcome measure.
OS Benefits in a High-Risk Population Randomization up to 107 months High-risk population included but was not limited to participants carrying deletion (del)17, t(4:14), t(14:16), amplification (ampl) 1q, del13, or del1p. OS was measured as the time from the date of randomization to the date of death.
PFS Benefits in a High-Risk Population Randomization up to 107 months High-risk population included but not be limited to participants carrying deletion (del)17, t(4:14), t(14:16), amplification (ampl) 1q, del13, or del1p. PFS was defined as the time from the date of randomization to the date of first documentation of PD, as evaluated by an independent review committee according to IMWG criteria, or death due to any cause (whichever occurs first). PD is defined as ≥25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be \>10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be ≥10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Score Baseline up to EOT (up to Month 24) ECOG performance status assesses a participant's performance status on a 6-point scale ranging from 0=fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. Lower scores indicate improvement.
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) or Serious Adverse Events (SAEs) Up to 107 months An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation subject administered a drug. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital abnormality or birth defect, an important medical event.
Number of Participants With Markedly Abnormal Clinical Laboratory Values Reported as TEAEs Up to 107 months Laboratory tests included chemistry, hematology and urinalysis. Abnormal laboratory value was assessed as an AE if the value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Domain Score Baseline up to EOT (up to Month 24) The EORTC QLQ-C30 is a 30-item questionnaire used to assess the health-related quality of life of cancer patients. GHS/QoL domain is based on questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") of the EORTC QLQ-C30 where the study participants' self-reported responses to the questions on a 7-point scale (1=very poor to 7=excellent). The raw GHS/QoL domain scores were linearly transformed to a scale ranging 0 (worse outcome) to 100 (best outcome), with higher scores indicating better quality of life. The change from baseline in EORTC QLQ-C30 GHS/QoL domain was evaluated by treatment group.
Plasma Concentration of Ixazomib Day 1 of Cycle 1: 1 hour and 4 hours post-dose; Predose on Days 8 and 15 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3 through 10 (each cycle length= 28 days) Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) were measured using a validated Liquid Chromatography-tandem Mass Spectrometry (LC/MS/MS) assay.
Time to Resolution of Peripheral Neuropathy (PN) Events Up to 107 months Peripheral neuropathy is defined as the TEAE in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as improved if the event improves from the maximum grade. That is, all the grades recorded after the maximum grade is less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.
Time to Improvement of PN Events Up to 107 months PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. A PN event is considered as improved if the event improves from the maximum grade. That is, all the grades recorded after the maximum grade is less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.
Trial Locations
- Locations (227)
Elisabethinen Hospital Linz
🇦🇹Linz, Austria
Hospital Iturraspe
🇦🇷Santa Fe, Argentina
Penn State Health Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Austin Health
🇦🇺Heidelberg, Victoria, Australia
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Nagoya City University Hospital
🇯🇵Nagoya-City, Japan
Asan Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Del-pesti Centrumkorhaz- Orszagos Hematologiai es Infektologiai Intezet
🇭🇺Budapest, Hungary
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Niigata, Japan
Toyohashi Municipal Hospital
🇯🇵Toyohashi-City, Japan
Vestre Viken HF Sykehuset Asker Og Barum
🇳🇴Gjelta, Oppland, Norway
National Hospital Organization Sendai Medical Center
🇯🇵Sendai, Miyagi, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya, Japan
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
C.H. Regional Reina Sofia - PPDS
🇪🇸Cordoba, Spain
Kings College Hospital
🇬🇧London, London, City Of, United Kingdom
Saitama Medical Center
🇯🇵Kawagoe-city, Saitama, Japan
Kyushu University Hospital
🇯🇵Fukuoka-City, Japan
National Hospital Organization Disaster Medical Center
🇯🇵Tachikawa, Japan
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Stavanger Universitetssykehus
🇳🇴Stavanger, Norway
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Complejo Asistencial Universitario de Salamanca H. Clinico
🇪🇸Salamanca, Spain
National Hospital Organaization Shibukawa Medical Center
🇯🇵Shibukawa, Japan
Erasmus MC
🇳🇱Rotterdam, Netherlands
Imperial College Healthcare NHS Trust
🇬🇧London, London, City Of, United Kingdom
Pamukkale Universitesi Tip Fakultesi Hastanesi
🇹🇷Denizli, Turkey
Karadeniz Technical University Faculty of Medicine
🇹🇷Trabzon, Turkey
Medical Oncology Centre of Rosebank
🇿🇦Johannesburg, Gauteng, South Africa
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Spain
Ankara University Medical Faculty PPDS
🇹🇷Ankara, Turkey
Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
🇬🇧London, London, City Of, United Kingdom
Singleton Hospital - PPDS
🇬🇧Swansea, United Kingdom
Hospital Universitario Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Madrid, Communidad Delaware, Spain
Universitatsspital Basel
🇨🇭Basel, Basel-Stadt (de), Switzerland
Clinica Universidad Navarra
🇪🇸Pamplona, Navarra, Spain
University College London Hospitals (UCLH)
🇬🇧London, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, Yorkshire, United Kingdom
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
🇹🇷Ankara, Turkey
Erciyes Universitesi Tip Fakultesi Hastanesi
🇹🇷Kayseri, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
🇹🇷Istanbul, Turkey
Azienda Ospedaliera S Maria Di Terni
🇮🇹Terni, Umbria, Italy
Hospital Das Clinicas Da Universidade Federal de Minas Gerais
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Singapore General Hospital (SGH)
🇸🇬Singapore, Singapore
Chang Gung Medical Foundation-Kaoshiung Branch
🇨🇳Kaohsiung, Taiwan
Japanese Red Cross Medical Center
🇯🇵Shibuya-ku, Tokyo, Japan
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Chulalongkorn University
🇹🇭Bangkok, Krung Thep Maha Nakhon-Bangkok, Thailand
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
National Cancer Center
🇰🇷Goyang, Gyeonggido, Korea, Republic of
Sanatorio Britanico de Rosario
🇦🇷Rosario, Santa Fe, Argentina
Klinik Ottakring (fruher: Wilhelminenspital)
🇦🇹Wien, Austria
Centre Hospitalier Jolimont-Lobbes
🇧🇪La Louviere, Hainaut, Belgium
Hospital de Braga
🇵🇹Braga, Portugal
Universitatsspital Zurich
🇨🇭Zurich, Zurich (de), Switzerland
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
MNPE Kyiv Center of Bone Marrow Transplantation of executive body of Kyiv council
🇺🇦Kyiv, Ukraine
Salzburger Landeskliniken
🇦🇹Salzburg, Austria
Chiba University Hospital
🇯🇵Chiba, Tokyo, Japan
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Shinjuku, Tokyo, Japan
Albert Schweitzer Ziekenhuis
🇳🇱Dordrecht, Zuid-Holland, Netherlands
St. Olav's University Hospital
🇳🇴Trondheim, Sor-Trondelag, Norway
Wojskowy Instytut Medyczny
🇵🇱Warszawa, Mazowieckie, Poland
Szpital Specjalistyczny w Brzozowie
🇵🇱Brzozow, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
🇵🇱Lodz, Poland
Instituto de Hematologia Y Medicina Clinica Dr Ruben Davoli
🇦🇷Rosario, Santa Fe, Argentina
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hospital Italiano de La Plata
🇦🇷La Plata, Buenos Aires, Argentina
Centre Hospitalier Universitaire Ambroise Pare
🇧🇪Mons, Hainaut, Belgium
Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo Leon, Mexico
VU Medisch Centrum
🇳🇱Amsterdam, Noord-Holland, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
🇵🇱Chorzow, Slaskie, Poland
Centro Hospitalar E Universitario de Coimbra EPE
🇵🇹Coimbra, Portugal
National University Hospital
🇸🇬Singapore, Singapore
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan City, Taiwan
Herlev Hospital
🇩🇰Herlev, Capital, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Odense Universitetshospital
🇩🇰Odense, Denmark
Vejle Sygehus
🇩🇰Vejle, Denmark
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University Health Network
🇨🇦Toronto, Ontario, Canada
Universitatsklinikum Wurzburg
🇩🇪Wurzburg, Bayern, Germany
LMU Klinikum der Universitat Munchen
🇩🇪Munchen, Bayern, Germany
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Icon Cancer Care South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Sanatorio Parque de Rosario
🇦🇷Rosario, Santa Fe, Argentina
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Instituto de Oncologia Do Parana
🇧🇷Curitiba, Parana, Brazil
Allgemeines Krankenhaus der Stadt Wien
🇦🇹Wien, Austria
UZ Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
AZ Sint-Jan AV
🇧🇪Brugge, West-Vlaanderen, Belgium
ZNA Middelheim
🇧🇪Antwerpen, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Hospital de Clinicas de Passo Fundo
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
🇧🇷Curitiba, Parana, Brazil
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Instituto Joinvilense de Hematologia E Oncologia
🇧🇷Joinville, Santa Catarina, Brazil
Centro de Pesquisas Oncologicas
🇧🇷Florianopolis, Santa Catarina, Brazil
Instituto Nacional de Cancer
🇧🇷Rio De Janeiro, Brazil
Mae de Deus Center Hospital Giovanni Battista
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Amaral Carvalho
🇧🇷Jau, Sao Paulo, Brazil
Universidade Federal do Rio de Janeiro - UFRJ
🇧🇷Rio de Janeiro, Brazil
Hospital de Base Da FAMERP
🇧🇷Sao Jose Do Rio Preto, Sao Paulo, Brazil
Irmandade Da Santa Casa de Misericordia de Sao Paulo
🇧🇷Sao Paulo, Brazil
Hospital Israelita Albert Einstein
🇧🇷Sao Paulo, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
🇧🇷Sao Paulo, Brazil
MUHC-Glen Site
🇨🇦Montreal, Quebec, Canada
Fundacion Valle Del Lili
🇨🇴Cali, Valle Del Cauca, Colombia
Instituto Nacional de Cancerologia Colombia
🇨🇴Bogota, Cundinamarca, Colombia
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Colombia
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Praha 2, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Kralovehradeck Kraj, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha, Czechia
Aalborg Universitetshospital
🇩🇰Aalborg, Nordjylland, Denmark
Sjallands Universitetshospital, Roskilde
🇩🇰Roskilde, Denmark
Aarhus Universitetshospital Arhus Sygehus
🇩🇰Aarhus N, Denmark
Hopital Antoine Beclere
🇫🇷Clamart, Hauts-de-Seine, France
CHRU Lille
🇫🇷Lille, Nord, France
Hotel Dieu - Nantes
🇫🇷Nantes, Loire-Atlantique, France
Hopital Universitaire Dupuytren
🇫🇷Limoges, France
Groupe Hospitalier Necker Enfants Malades
🇫🇷Paris, France
University Clinic Heidelberg
🇩🇪Heidelberg, Baden-Wurttemberg, Germany
Klinikum Mannheim Universitatsklinikum gGmbH
🇩🇪Mannheim, Baden-Wurttemberg, Germany
Klinikum Darmstadt GmbH
🇩🇪Darmstadt, Hessen, Germany
Klinikum Frankfurt Hochst GmbH
🇩🇪Frankfurt am Main, Hessen, Germany
Pius Hospital Oldenburg
🇩🇪Oldenburg, Niedersachsen, Germany
Universitatsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitatsklinikum Bonn
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Evangelisches Krankenhaus Essen Werden gGmbH
🇩🇪Essen, Nordrhein-Westfalen, Germany
Katholisches Krankenhaus Hagen gGmbH
🇩🇪Hagen, Nordrhein-Westfalen, Germany
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Uniklinik Koln
🇩🇪Koln, Nordrhein-Westfalen, Germany
Universitatsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Sachsen, Germany
Charite - Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
Universitatsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
KRH Klinikum Siloah-Oststadt-Heidehaus
🇩🇪Hannover, Germany
Klinikum der Stadt Ludwigshafen gGmbH
🇩🇪Ludwigshafen, Germany
Universitatsklinikum Tubingen
🇩🇪Tubingen, Germany
Evangelismos General Hospital of Athens
🇬🇷Athens, Attiki, Greece
Alexandra Hospital
🇬🇷Athens, Greece
Laiko General Hospital of Athens
🇬🇷Athens, Attiki, Greece
Georgios Papanikolaou General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Soroka University Medical Centre
🇮🇱Be'er Sheva, Israel
Somogy Megyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvar, Hungary
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Rambam Medical Center - PPDS
🇮🇱Haifa, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Hadassah Medical Center PPDS -
🇮🇱Jerusalem, Israel
Rabin Medical Center - PPDS
🇮🇱Petach Tikva, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Sheba Medical Center - PPDS
🇮🇱Ramat-Gan, Israel
ZIV Medical Center
🇮🇱Safed, Israel
Tel Aviv Sourasky Medical Center PPDS
🇮🇱Tel Aviv, Israel
Fondazione IRCCS Policlinico San Matteo di Pavia
🇮🇹Pavia, Lombardia, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
🇮🇹Ancona, Marche, Italy
Presidio Ospedaliero di Pescara
🇮🇹Pescara, Abruzzo, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Lazio, Italy
IRCCS Centro Di Riferimento Oncologico Della Basilicata
🇮🇹Rionero In Vulture, Potenza, Italy
Shamir Medical Center Assaf Harofeh
🇮🇱Tzrifin, Israel
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
🇮🇹Bologna, Italy
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
🇮🇹Brescia, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
IRCCS Az. Osp. Universitaria San Martino- IST
🇮🇹Genova, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS
🇮🇹Meldola, Italy
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
🇮🇹Milano, Italy
Ospedale Infermi di Rimini
🇮🇹Rimini, Italy
Iwate Medical University Hospital
🇯🇵Morioka-shi, Iwate, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama-City, Okayama, Japan
Juntendo University Hospital
🇯🇵Bunkyo, Tokyo, Japan
Gachon University Gil Medical Center Pharmacy
🇰🇷Incheon, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System - PPDS
🇰🇷Seoul, Korea, Republic of
Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS
🇲🇽Guadalajara, Jalisco, Mexico
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
🇵🇱Wroclaw, Dolnoslaskie, Poland
Oslo Universitetssykehus HF, Ulleval
🇳🇴Oslo, Norway
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Centro Hospitalar de Sao Joao, E.P.E.
🇵🇹Porto, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
🇵🇹Porto, Portugal
Akademiska Sjukhuset I Uppsala
🇸🇪Uppsala, Sweden
Mary Potter Oncology Centre
🇿🇦Pretoria, Gauteng, South Africa
Albert Alberts Stem Cell Transplant Centre
🇿🇦Pretoria, Gauteng, South Africa
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Institut Catala d'Oncologia Girona
🇪🇸Girona, Spain
Hospital Universitario La Paz - PPDS
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro CIOCC
🇪🇸Madrid, Spain
Skanes Universitetssjukhus Lund
🇸🇪Lund, Skane Lan, Sweden
Hospital Universitario Virgen del Rocio - PPDS
🇪🇸Sevilla, Spain
Helsingborg Lasarett
🇸🇪Helsingborg, Skane Lan, Sweden
Sahlgrenska Universitetssjukhuset
🇸🇪Goteborg, Vastra Gotalands Lan, Sweden
Karolinska Universitetssjukhuset Huddinge
🇸🇪Stockholm, Sweden
Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital
🇨🇳Taipei, Taiwan
Phramongkutklao Hospital
🇹🇭Bangkok, Krung Thep Maha Nakhon-Bangkok, Thailand
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷Ankara, Turkey
Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
St James University Hospital
🇬🇧Leeds, Yorkshire, United Kingdom
Royal Marsden Hospital - Surrey
🇬🇧Sutton, Surrey, United Kingdom
University Hospitals Leicester
🇬🇧Leicester, United Kingdom
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Kobe City Medical Center General Hospital
🇯🇵Kobe-City, Hyogo, Japan
Universitatsklinikum Ulm
🇩🇪Ulm, Baden-Wurttemberg, Germany
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Madrid, Spain
Mayo Clinic - PPDS
🇺🇸Rochester, Minnesota, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States