A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)

Phase 3

Completed

Conditions: Multiple Myeloma

Interventions: Drug: Placebo
Drug: Ixazomib

Registration Number: NCT02312258

Lead Sponsor: Takeda

Brief Summary: The purpose of this study is to determine the effect of ixazomib maintenance therapy on progression free survival (PFS) compared with placebo, in participants with NDMM who have had a major response (complete response \[CR\], very good partial response \[VGPR\], or partial response \[PR\]) to initial therapy and who have not undergone SCT.

Detailed Description: The drug being tested in this study is called ixazomib citrate. Ixazomib citrate is being tested to slow progressive disease (PD) and improve overall survival in people who have NDMM who have had a major positive response to initial therapy and have not undergone SCT. This study will look at the effect of ixazomib citrate has on the length of time that participants are free of PD and their overall survival.

The study will enrol approximately 700 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 3:2 ratio to Ixazomib or matching placebo groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Ixazomib citrate initiates at 3 mg which will be escalated to 4 mg with cycle 5 day 1

* 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. The treatment period will be approximately 24 months (equivalent to 26 cycles) or until patients experience PD or unacceptable toxicities, whichever occurs first.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 78 to 106 months. Participants will make 28 visits to the clinic during the treatment period and will continue to make follow-up visits every 4 weeks until the next line of therapy begins. Participants will also be contacted by telephone every 12 weeks after last treatment visit for a follow-up assessment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 706

Inclusion Criteria

Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.
Completed 6 to 12 months (± 2 weeks) of initial therapy, during which the participant was treated to best response, defined as the best response maintained for 2 cycles after the M-protein nadir is reached.
Documented major response (PR, VGPR, CR) according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.
Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- 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, 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] and withdrawal are not acceptable methods of contraception.)
Male participants, even if surgically sterilized (that is, 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, OR
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
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.
Complete documentation of the details of the initial therapy before randomization including cytogenetics and International Staging System (ISS) is available.
Eastern Cooperative Oncology Group Performance Status of 0 to 2.
Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
Is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
Must meet the following clinical laboratory criteria at study entry:
- Absolute neutrophil count (ANC) greater than or equal to (≥) 1,000 per cubic millimeter (/mm^3) without growth factor support 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 less than or equal to (≤) 1.5*the upper limit of the normal range (ULN).
- Alanine aminotransferase and aspartate aminotransferase ≤ 3*ULN.
- Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min) (using the Cockcroft-Gault equation).

Exclusion Criteria

Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
Prior SCT.
Radiotherapy within 14 days before randomization.
Diagnosed or treated for another malignancy within 5 years before randomization or previous diagnosis with another malignancy. 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, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled 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 St. John's wort within 14 days before randomization.
Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
Comorbid systemic illnesses or other severe concurrent disease that, 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 (example, PN that is Grade 1 with pain or Grade 2 or higher of any cause).
Psychiatric illness or 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 30 days before randomization.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.
Ixazomib	Ixazomib	Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	From randomization until PD or death (up to 52 months)	PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD is defined as, increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/ deciliter (dL)); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved free light chains (FLC) levels (absolute increase \>10 mg/dL); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia (corrected serum calcium \>11.5mg/dL).

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival 2 (PFS2)	From the date of randomization to every 12 weeks until second PD or death (up to 88 months)	PFS2 is defined as the time from the date of randomization to objective PD on next-line treatment using IMWG criteria, or death due to any cause, whichever occurred first.
Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period	Up to 27 months	Response was assessed according to IMWG criteria based on IRC assessment. Best response included PR, VGPR and CR. PR= \>=50% reduction of serum M protein and \>=90% or \<200 mg reduction urinary M protein in 24-hour, or \>50% decrease in difference between involved and uninvolved FLC levels, or \>50% reduction in bone marrow plasma cells, if bone marrow plasma cells \>30% and \>50% reduction in size of soft tissue plasmacytomas at baseline. VGPR= \>90% reduction (\<100 mg/24-hour) in serum M-protein + urine M-protein detectable by immunofixation but not on electrophoresis. Complete response= \>5% plasma cells in myelogram with absence of paraprotein in serum and urine according to immunofixation.
Time to Next Line Therapy (TTNT)	From randomization until PD or death (up to 52 months)	TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy.
Duration of Next-line Therapy	From randomization until PD or death (up to 52 months)	Duration of next-line therapy is defined as the time from the date of the first dose of the next line of antineoplastic therapy coming after study treatment to the date of the last dose.
Percentage of Participants Who Develop a New Primary Malignancy	From randomization until PD or death (up to 52 months)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS)	Baseline, Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26 (cycle length=28 days)	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The change from baseline in GHS (EORTC QLQ-C30) score is presented. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1=very poor to 7=excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall GHS.
Time to Progression (TTP)	From randomization until PD or death (up to 52 months)	TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria.
Time to Improvement of PN Events	Up to 52 months	PN is defined as the event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the improvement date or the day before and after. Time to improvement was defined as the time from the initial onset date (inclusive) to the improvement of event.
PFS in a High-risk Population	From randomization until PD or death (up to 52 months)	High-risk population included but not be limited to participants carrying del17, t(4;14), t(14;16). PFS was defined as the time from the date of randomization to the date of first documentation of PD or death from any cause.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status	Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26, progression free survival follow-up (PFSFU)- Visit 37 and progressive disease follow-up (PDFU)- Visit 26 (cycle length=28 days)	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 grades indicate improvement.
Correlation Between Frailty Status and PFS and OS	From randomization up to 52 months	Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first, assessed for up to 52 months in this outcome measure. OS will be measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure.
Overall Survival (OS)	From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)	OS was measured as the time from the date of randomization to the date of death.
Time to End of the Next-line of Therapy After Study Treatment	From randomization until PD or death (up to 52 months)	Time to end of the next line of therapy is 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.
Correlation of MRD Status With PFS and OS	From randomization up to 52 months	PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurred first, assessed for up to 52 months in this outcome measure. OS was measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure. Participants with various types of known MRD status were pooled together for analysis of overall survival in this outcome measure.
OS in a High-risk Population	From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)	High-risk population included but not be limited to participants carrying cytogenetic deletion (del)17, translocation \[t\](4;14), t(14;16). OS was measured as the time from the date of randomization to the date of death.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	First dose of study drug through 30 days after last dose of study drug (up to 88 months)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAEs were defined as events that occurred after administration of the first dose of ixazomib or placebo through 30 days after the last dose of ixazomib or placebo. A SAE means any untoward medical occurrence that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was considered medically significant.
Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative	Up to 52 months	Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry. MRD negativity was defined as absence of MRD and MRD positivity was defined as presence of MRD. MRD was assessed by 8-color flow cytometry with the IMWG recommended sensitivity of 10\^-5.
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib	Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6 to 10 (Day 1 pre-dose) (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 52 months	PN is defined as the 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 was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution was defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.

Trial Locations

Locations (273): Clinica Sao Germano
🇧🇷
Sao Paulo, Brazil
North County Oncology Medical Clinic Inc
🇺🇸
Oceanside, California, United States
Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" (CEMIC)
🇦🇷
Buenos Aires, Ciudad Autonoma De BuenosAires, Argentina
Universidade Estadual de Campinas
🇧🇷
Campinas, Sao Paulo, Brazil
Sanatorio Allende S.A.
🇦🇷
Cordoba, Argentina
Universitatsklinikum Innsbruck
🇦🇹
Innsbruck, Tirol, Austria
Clinical Research Alliance Inc
🇺🇸
New York, New York, United States
Ventura County Hematology Oncology Specialists
🇺🇸
Oxnard, California, United States
Emad Ibrahim, MD, Inc
🇺🇸
Redlands, California, United States
Universitair Ziekenhuis Brussel - PIN
🇧🇪
Brussel, Brussels, Belgium
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
🇧🇷
Curitiba, Parana, Brazil
Liga Norte Riograndense Contra O Cancer
🇧🇷
Natal, Rio Grande Do Norte, Brazil
Faculdade de Medicina Do ABC
🇧🇷
Santo Andre, Sao Paulo, Brazil
Hospital Iturraspe
🇦🇷
Santa Fe, Argentina
New York Presbyterian Hospital - Weill-Cornell
🇺🇸
New York, New York, United States
Hospital Das Clinicas Da Universidade Federal de Goias
🇧🇷
Goiania, Goias, Brazil
Tufts Medical Center - PPDS
🇺🇸
Boston, Massachusetts, United States
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Kralovehradeck Kraj, Czechia
Fakultni nemocnice Ostrava
🇨🇿
Ostrava, Czechia
Universitatsklinikum Ulm
🇩🇪
Ulm, Baden-Wurttemberg, Germany
Hamatologische Onkologische Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter
🇩🇪
Augsburg, Bayern, Germany
Instituto Nacional de Cancerologia Colombia
🇨🇴
Bogota, Cundinamarca, Colombia
Hopital Haut Leveque
🇫🇷
Pessac, France
Beijing Chaoyang Hospital Capital Medical University
🇨🇳
Beijing, China
Hopital Saint Vincent de Paul GHICL
🇫🇷
Lille, France
CHRU Lille
🇫🇷
Lille, France
Hopital de la Pitie Salpetriere
🇫🇷
Paris, France
Fakultni nemocnice Olomouc
🇨🇿
Olomouc, Czechia
Fakultni nemocnice Brno
🇨🇿
Brno, Czechia
CHRU Nancy
🇫🇷
Vandoeuvre-les-nancy, Meurthe-et-Moselle, France
McGill University Health Center
🇨🇦
Montreal, Quebec, Canada
Medizinisches Versorgungszentrum Onkologischer Schwerpunkt
🇩🇪
Berlin, Germany
Shanghai Chang Zheng Hospital
🇨🇳
Shanghai, China
Hopital Jean Bernard
🇫🇷
Poitiers, France
Peking University Third Hospital
🇨🇳
Beijing, China
Charite - Universitatsmedizin Berlin
🇩🇪
Berlin, Germany
Gemeinschaftspraxis fur Hamatologie und Onkologie
🇩🇪
Munster, Nordrhein-Westfalen, Germany
Klinikum Landshut
🇩🇪
Landshut, Germany
Clinical Hospital Center Zagreb - PPDS
🇭🇷
Zagreb, Croatia
Universitat Des Saarlandes
🇩🇪
Homburg, Saarland, Germany
CHRU Dijon Complexe Du Bocage
🇫🇷
Dijon, France
Schwarzwald Baar Klinkum Villingen-Schwenningen GmbH
🇩🇪
Villingen-Schwenningen, Baden-Wurttemberg, Germany
Severance Hospital Yonsei University Health System - PPDS
🇰🇷
Seoul, Korea, Republic of
Vseobecna fakultni nemocnice v Praze
🇨🇿
Praha 2, Czechia
Universitatsklinikum Essen
🇩🇪
Essen, Nordrhein-Westfalen, Germany
Praxis Pihusch Medizinisches Versorgungszentrum GbR
🇩🇪
Rosenheim, Germany
LMU Klinikum der Universitat Munchen
🇩🇪
Munchen, Bayern, Germany
Meir Medical Center
🇮🇱
Kfar Saba, Israel
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center - PPDS
🇰🇷
Seoul, Korea, Republic of
Klinikum rechts der Isar der Technischen Universitat Munchen
🇩🇪
Munchen, Germany
Pius Hospital Oldenburg
🇩🇪
Oldenburg, Niedersachsen, Germany
Evangelismos General Hospital of Athens
🇬🇷
Athens, Greece
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
🇩🇪
Mainz, Rheinland-Pfalz, Germany
Azienda Ospedaliero Universitaria di Parma
🇮🇹
Parma, Italy
Skanes Universitetssjukhus Lund
🇸🇪
Lund, Sweden
Ankara University Medical Faculty PPDS
🇹🇷
Ankara, Turkey
Hospital Universitario Quironsalud Madrid
🇪🇸
Pozuelo De Alarcon, Madrid, Communidad Delaware, Spain
Hospital Universitario de La Princesa
🇪🇸
Madrid, Spain
Shengjing Hospital of China Medical University
🇵🇱
Bydgoszcz, Kujawsko-pomorskie, Poland
Hospital Clinic de Barcelona
🇪🇸
Barcelona, Spain
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
🇹🇷
Istanbul, Turkey
Hospital Universitario HM Sanchinarro CIOCC
🇪🇸
Madrid, Spain
Gachon University Gil Medical Center
🇰🇷
Incheon, Korea, Republic of
Centro Hospitalar de Sao Joao EPE
🇵🇹
Porto, Portugal
Leicester Royal Infirmary
🇬🇧
Leicester, United Kingdom
University Clinical Center of Serbia - PPDS
🇬🇧
Southall, United Kingdom
Singleton Hospital - PPDS
🇬🇧
Swansea, United Kingdom
Dokuz Eylul University Medical Faculty
🇹🇷
Izmir, Turkey
Hospital Universitario Infanta Leonor
🇪🇸
Madrid, Spain
Hospital General Universitario Morales Meseguer
🇪🇸
Murcia, Spain
Bristol Haematology and Oncology Centre
🇬🇧
Bristol, Bristol, City Of, United Kingdom
Southmead Hospital
🇬🇧
Bristol, United Kingdom
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷
Ankara, Turkey
Centro Hospitalar do Porto - Hospital de Santo Antonio
🇵🇹
Porto, Portugal
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Complejo Asistencial Universitario de Salamanca H. Clinico
🇪🇸
Salamanca, Spain
Kings College Hospital
🇬🇧
London, London, City Of, United Kingdom
Hillingdon Hospital
🇬🇧
Uxbridge, London, City Of, United Kingdom
Royal United Hospital
🇬🇧
Bath, United Kingdom
Northwick Park Hospital
🇬🇧
Middlesex, United Kingdom
The Royal Oldham Hospital - PPDS
🇬🇧
Oldham, United Kingdom
Robert A Moss MD FACP Inc
🇺🇸
Fountain Valley, California, United States
Saint Agnes Hospital - Baltimore - Hunt - PPDS
🇺🇸
Baltimore, Maryland, United States
UCLA Medical Hematology and Oncology
🇺🇸
Los Angeles, California, United States
American Oncology Partners of Maryland, PA
🇧🇷
Passo Fundo, Rio Grande Do Sul, Brazil
Winship Cancer Institute, Emory University
🇺🇸
Atlanta, Georgia, United States
Cancer Care of WNC PA
🇺🇸
Asheville, North Carolina, United States
UPMC Cancer Pavillion
🇺🇸
Pittsburgh, Pennsylvania, United States
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
John H. Stroger Jr. Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
🇧🇷
Salvador, Bahia, Brazil
Medical Oncology Centre of Rosebank
🇿🇦
Johannesburg, Gauteng, South Africa
Global Cancer Research Institute (GCRI), Inc.
🇺🇸
San Jose, California, United States
Siouxland Hematology - Oncology Associates LLP
🇺🇸
Sioux City, Iowa, United States
New England Cancer Specialists
🇺🇸
Scarborough, Maine, United States
Herbert-Herman Cancer Center
🇺🇸
Lansing, Michigan, United States
Swedish Cancer Institute
🇺🇸
Seattle, Washington, United States
HOPE Cancer Center of East Texas
🇺🇸
Tyler, Texas, United States
W VA University Mary Babb Randolph Cancer Center
🇺🇸
Morgantown, West Virginia, United States
Hospital Universitario Austral
🇦🇷
Buenos Aires, Ciudad Autonoma De BuenosAires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷
Buenos Aires, Ciudad Autonoma De BuenosAires, Argentina
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Brussels, Belgium
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Fundacao PIO XII
🇧🇷
Barretos, Sao Paulo, Brazil
Instituto Nacional de Cancer
🇧🇷
Rio de Janeiro, Brazil
Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto
🇧🇷
Sao Jose Do Rio Preto, Brazil
Instituto de Ensino E Pesquisa Sao Lucas
🇧🇷
Sao Paulo, Brazil
Hospital Sirio Libanes
🇧🇷
Sao Paulo, Brazil
Ealing Hospital
🇧🇷
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
Hospital Santa Marcelina
🇧🇷
Sao Paulo, Brazil
William Osler Health Centre
🇨🇦
Brampton, Ontario, Canada
Royal Victoria Regional Health Centre
🇨🇦
Barrie, Ontario, Canada
Instituto Nacional Del Cancer
🇨🇱
Santiago, Chile
Centro Internacional de Estudios Clinicos
🇨🇱
Santiago, Chile
Centro de Investigaciones Clinicas Vina del Mar
🇨🇱
Vina Del Mar, Chile
Ruijin Hospital Shanghai Jiaotong University School of Medicine
🇨🇳
Shanghai, Shanghai, China
Fakultni nemocnice Kralovske Vinohrady
🇨🇿
Prague, Praha, Hlavni Mesto, Czechia
Internistisch Hamatologische und Internistische Praxis
🇩🇪
Herrsching am Ammersee, Bayern, Germany
Onkologie Aschaffenburg
🇩🇪
Aschaffenburg, Germany
Gemeinschaftspraxis Dr. med. R. Schlag & Dr. med. B. Schottker & Dr. med. J. Haas
🇩🇪
Wurzburg, Germany
Tel Aviv Sourasky Medical Center
🇮🇱
Tel Aviv, Israel
Baruch Padeh Poriya Medical Center
🇮🇱
Tiberias, Israel
AORN A Cardarelli
🇮🇹
Napoli, Campania, Italy
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷
Seoul, Korea, Republic of
MTZ Clinical Research Sp z o o - PRATIA - PPDS
🇵🇱
Warszawa, Mazowieckie, Poland
Albert Alberts Stem Cell Transplant Centre
🇿🇦
Pretoria, Gauteng, South Africa
Mary Potter Oncology Centre
🇿🇦
Pretoria, Gauteng, South Africa
Clinica Universidad Navarra
🇪🇸
Pamplona, Navarra, Spain
Karolinska Universitetssjukhuset Huddinge
🇸🇪
Stockholm, Sodermanlands Lan, Sweden
Sahlgrenska Universitetssjukhuset
🇸🇪
Goteborg, Vastra Gotalands Lan, Sweden
Chulalongkorn University
🇹🇭
Bangkok, Thailand
Hammersmith Hospital
🇬🇧
London, London, City Of, United Kingdom
University Clinical Center Nis
🇬🇧
Cardiff, United Kingdom
Ulster Hospital
🇬🇧
Belfast, United Kingdom
West Middlesex University Hospital
🇬🇧
Isleworth, United Kingdom
Manchester Royal Infirmary - PPDS
🇬🇧
Manchester, United Kingdom
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳
Hangzhou, China
Renji Hospital Shanghai Jiaotong University School of Medicine
🇨🇳
Shanghai, China
Peking Union Medical College Hospital
🇨🇳
Beijing, China
Hospital de Clinicas de Passo Fundo
🇨🇳
Nanjing, Jiangsu, China
Hospital São Rafael
🇨🇳
Shenyang, China
Second Hospital of Shanxi Medical University
🇨🇳
Taiyuan, China
James Lind Centro de Investigación del Cáncer
🇨🇳
Wuhan, China
Associacao Hospital de Caridade Ijui
🇧🇷
Ijui, Rio Grande Do Sul, Brazil
Universidade de Caxias do Sul
🇧🇷
Caxias Do Sul, Rio Grande Do Sul, Brazil
Azienda Ospedaliera S Maria Di Terni
🇮🇹
Terni, Umbria, Italy
Hospital Moinhos de Vento
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Kent and Canterbury Hospital
🇬🇧
Canterbury, Kent, United Kingdom
Mae de Deus Center Hospital Giovanni Battista
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
🇩🇰
København, Capital, Denmark
Aarhus Universitetshospital Århus Sygehus
🇩🇰
Aarhus N, Denmark
Regionshospitalet Holstebro
🇩🇰
Holstebro, Denmark
Odense Universitetshospital
🇩🇰
Odense, Denmark
Clinical Hospital Dubrava
🇭🇷
Zagreb, Grad Zagreb, Croatia
The Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Japanese Red Cross Narita Hospital
🇯🇵
Narita-shi, Japan
Hospital Amaral Carvalho
🇨🇱
Temuco, Araucanía, Chile
University of Athens Medical School - Regional General Hospital Alexandra
🇬🇷
Athens, Attiki, Greece
University General Hospital of Ioannina
🇬🇷
Ioannina, Greece
Debreceni Egyetem Klinikai Kozpont
🇭🇺
Debrecen, Hungary
Yamanashi Prefectural Central Hospital
🇯🇵
Yamanashi, Japan
St Vincents Hospital Melbourne - PPDS
🇦🇺
Fitzroy, Victoria, Australia
Instituto Joinvilense de Hematologia E Oncologia
🇧🇷
Joinville, Santa Catarina, Brazil
Medizinische Universitat Wien (Medical University of Vienna)
🇦🇹
Wien, Austria
UZ Brussel
🇧🇪
Brussel, Brussels, Belgium
Paracelsus Medizinische Privatuniversitat
🇦🇹
Salzburg, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹
Wels, Austria
Hospital Universitario San Ignacio
🇨🇴
Bogota, Distrito Capital De Bogota, Colombia
Hospital Pablo Tobon Uribe
🇨🇴
Medellin, Antioquia, Colombia
Hotel Dieu
🇫🇷
Nantes, Loire-Atlantique, France
Clinical Hospital Center Rijeka
🇭🇷
Rijeka, Croatia
Hopital Antoine Beclere
🇫🇷
Clamart, Hauts-de-Seine, France
Klinika Hematologii, Szpital Uniwersytecki Nr 2 im. Jana Biziela w Bydgoszczy
🇭🇺
Budapest, Hungary
Semmelweis Egyetem
🇭🇺
Budapest, Hungary
University General Hospital of Larissa
🇬🇷
Larissa, Greece
Ogaki Municipal Hospital
🇯🇵
Ogaki, Gihu, Japan
National Hospital Organization Okayama Medical Center
🇯🇵
Okayama-city, Okayama, Japan
Oaxaca Site management Organization (OSMO) - PPDS
🇲🇽
Oaxaca, Mexico
Japanese Red Cross Medical Center
🇯🇵
Shibuya-ku, Tokyo, Japan
Theageneio Anticancer Oncology Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
Georgios Papanikolaou General Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
Rigshospitalet
🇮🇱
Beer Yaakov, Israel
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺
Szeged, Hungary
Shamir Medical Center Assaf Harofeh
🇮🇱
Be'er Sheva, Israel
Bnai Zion Medical Center
🇮🇱
Haifa, Israel
National Hospital Organization Kyushu Medical Center
🇯🇵
Fukuoka, Japan
Fukushima Medical University Hospital
🇯🇵
Fukushima-City, Japan
National Hospital Organization Mito Medical Center
🇯🇵
Ibaraki, Japan
Niigata Cancer Center Hospital
🇯🇵
Niigata-city, Japan
Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽
Monterrey, Nuevo Leon, Mexico
Hospital Garcia de Orta
🇵🇹
Almada, Portugal
City Center of MS Treatment based on Saint-Petersburg City Clinical Hospital #31
🇷🇺
St. Petersburg, Russian Federation
Clinical Hospital Center ''Bezanijska Kosa''
🇷🇸
Belgrade, Serbia
University Clinical Center Kragujevac
🇷🇸
Kragujevac, Serbia
Soroka University Medical Centre
🇷🇸
Nis, Serbia
Queen Alexandra Hospital
🇬🇧
Portsmouth, Hampshire, United Kingdom
Royal Marsden Hospital - Surrey
🇬🇧
Sutton, Surrey, United Kingdom
Hadassah Medical Center - PPDS
🇮🇱
Jerusalem, Israel
Rabin Medical Center - PPDS
🇮🇱
Petah Tikva, Israel
Chaim Sheba Medical Center
🇮🇱
Ramat Gan, Israel
Kobe City Medical Center General Hospital
🇯🇵
Kobe-City, Hyogo, Japan
Japanese Red Cross Nagoya Daiichi Hospital
🇯🇵
Nagoya, Japan
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
🇷🇸
Belgrade, Serbia
Assuta Medical Centers
🇮🇱
Tel Aviv, Israel
Hitachi General Hospital
🇯🇵
Hitachi, Ibaraki, Japan
Nara Hospital Kinki University Faculty of Medicine
🇯🇵
Ikoma-City, Nara, Japan
Juntendo University Hospital
🇯🇵
Bunkyo, Tokyo, Japan
IRCCS Az. Osp. Universitaria San Martino- IST
🇮🇹
Genova, Liguria, Italy
Kurume University Hospital
🇯🇵
Kurume, Japan
Shizuoka Cancer Center
🇯🇵
Nagaizumi-chō, Japan
National Hospital Organization Disaster Medical Center
🇯🇵
Tachikawa, Japan
Hospital Y Clinica OCA Sociedad Anonima de Capital Variable
🇲🇽
Monterrey, Nuevo Leon, Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
🇲🇽
Mexico City, Mexico
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
🇵🇹
Lisbon, Lisboa, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
🇵🇹
Porto, Portugal
Ramathibodi Hospital
🇹🇭
Bangkok, Krung Thep Maha Nakhon, Thailand
Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS
🇲🇽
Guadalajara, Jalisco, Mexico
Nagoya City University Hospital
🇯🇵
Nagoya, Japan
Osaka Saiseikai Nakatsu Hospital
🇯🇵
Osaka, Japan
Toyohashi Municipal Hospital
🇯🇵
Toyohashi, Japan
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
🇵🇱
Wroclaw, Poland
State Medical and Preventive Treatment Institution Kirov Regional Clinical Oncology Dispensary
🇷🇺
Kirov, Russian Federation
Stavropol Regional Clinical Oncology Centre Pyatigorsk Affiliate
🇷🇺
Pyatigorsk, Russian Federation
Ryazan Regional Clinical Hospital
🇷🇺
Ryazan, Russian Federation
Russian Research Institute of Hematology and Blood Transfusion
🇷🇺
St. Petersburg, Russian Federation
National University Hospital
🇸🇬
Singapore, Singapore
Kaohsiung Medical University Hospital
🇨🇳
Kaohsiung, Taiwan
Birmingham Heartlands Hospital
🇬🇧
West Malling, Birmingham, United Kingdom
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Belfast City Hospital
🇬🇧
Belfast, Antrim, United Kingdom
Royal Bournemouth Hospital
🇬🇧
Bournemouth, Dorset, United Kingdom
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
🇵🇱
Chorzow, Poland
Hospital de Braga
🇵🇹
Braga, Portugal
Champalimaud Cancer Center
🇵🇹
Lisboa, Portugal
Singapore General Hospital (SGH)
🇸🇬
Singapore, Singapore
Hospital Universitario Germans Trias i Pujol
🇪🇸
Badalona, Barcelona, Spain
Churchill Hospital
🇬🇧
Oxford, Oxfordshire, United Kingdom
Spital STS AG
🇨🇭
Thun, Switzerland
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
Maharaj Nakorn Chiang Mai Chiang Mai University
🇹🇭
Chiangmai, Thailand
New Cross Hospital
🇬🇧
Wolverhampton, Staffordshire, United Kingdom
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
🇮🇹
Brescia, Lombardia, Italy
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
🇮🇹
Milano, Lombardia, Italy
Ospedale Casa Sollievo Della Sofferenza IRCCS
🇮🇹
San Giovanni Rotondo, Puglia, Italy
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
🇮🇹
Catania, Sicilia, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹
Pisa, Toscana, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
🇮🇹
Bologna, Emilia-Romagna, Italy
Ospedale Infermi di Rimini
🇮🇹
Rimini, Emilia-Romagna, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
🇮🇹
Ancona, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹
Firenze, Italy
Ospedale Santa Maria Delle Croci
🇮🇹
Ravenna, Italy
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
🇮🇹
Torino, Italy
Karolinska Universitetssjukhuset Solna
🇸🇪
Stockholm, Sodermanlands Lan, Sweden
Groupe Hospitalier Necker Enfants Malades
🇫🇷
Paris, France
CHRU Rennes
🇫🇷
Rennes, France
Barts Health NHS Trust
🇬🇧
London, London, City Of, United Kingdom
University College London
🇬🇧
London, London, City Of, United Kingdom
Chelsea and Westminster NHS Trust
🇬🇧
London, United Kingdom
HEMORIO - Unidade de Pesquisa Clinica
🇧🇷
Rio De Janeiro, Brazil
Fundação Antônio Prudente - AC Camargo Câncer Center
🇧🇷
Rio De Janeiro, Brazil
National Cancer Center
🇰🇷
Goyang-si, Gyeonggido, Korea, Republic of
Hospital General Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
Appalachian Regional Healthcare
🇺🇸
Hazard, Kentucky, United States
Hospital de La Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
University Hospital of Wales -
🇺🇸
Bethesda, Maryland, United States
Central Coast Medical Oncology Corporation
🇺🇸
Santa Maria, California, United States
Frankston Hospital
🇦🇺
Frankston, Victoria, Australia
Hospital Das Clinicas Da UFMG
🇧🇷
Belo Horizonte, Minas Gerais, Brazil