Clinical trial NCT02303821: Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Official title: Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia (ALL)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) - Study Design & Execution Collaborator
name: Innovative Therapies For Children with Cancer Consortium
First posted: 2014-12-01
Enrollment: 141
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of Phase 1b of this study is to:

* Asses the safety, tolerability and activity of carfilzomib, alone and in combination with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL).
* Determine the maximum tolerated dose (MTD) and to recommend a phase 2 dose of carfilzomib in combination with induction chemotherapy.

The purpose of Phase 2 of this study is to compare the rate of complete remission (CR) of carfilzomib in combination with vincristine, dexamethasone, PEG asparaginase, daunorubicin (VXLD) at the end of induction therapy to an appropriate external control.


Eligibility criteria: Phase 1b Key Inclusion Criteria:

1. Age 21 years or younger at the time of initial ALL diagnosis and age \> 1 year at the time of study treatment initiation.
2. Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease.

   -To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:
   * Early first relapse (\< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
   * First refractory bone marrow relapse occurring any time after original diagnosis after achieving a CR (ie, ≥1 failed attempt to induce a second remission) OR
   * Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2 relapses) OR
   * Failing to achieve a CR from original diagnosis after at least 1 induction attempt
3. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
4. Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit of normal (ULN) according to age. If serum creatinine level is \> 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2.
5. Adequate liver function, defined as both of the following:

   * Total bilirubin ≤ 1.5 × institutional ULN except in the presence of Gilbert Syndrome
   * Alanine aminotransferase (ALT) ≤ 5 × institutional ULN
6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects \> 16 years old or ≤ 16 years old, respectively.

Phase 2 Inclusion Criteria:

1. Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated, except for standard of care local testing as permitted per protocol.
2. Age greater than or equal to 1 month to less than 21 years. Subjects greater than or equal to 18 years must have had their original diagnosis at less than 18 years of age.
3. Subjects must be diagnosed with relapsed or refractory relapsed ALL.
4. Subjects must have a documented first remission, less than 5% blasts in the bone marrow (M1 bone marrow) and no evidence of extramedullary disease.
5. T-cell ALL with bone marrow relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) or refractory relapse with or without extramedullary disease.

   OR B-cell ALL bone marrow relapse or refractory relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) after having received a targeted B-cell immune therapy (eg, blinatumomab, inotuzumab or a CAR-T therapy) with or without extramedullary disease..
6. Adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) less than or equal to 5 x ULN.
7. Adequate renal function: serum creatinine less than or equal to 1.5 x ULN or glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m\^2; or for children less than 2 years of age, greater than or equal to 50 mL/min/1.73 m\^2.
8. Adequate cardiac function: shortening fraction greater than or equal to 30% or ejection fraction greater than or equal to 50%.
9. Karnofsky (subjects greater than or equal to 16 years of age) or Lansky (subjects 12 months to less than 16 years of age) performance status greater than or equal to 50%.
10. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment (for example: recovery from gastrointestinal toxicity may occur more rapidly than less reversible organ toxicities such as sinusoidal obstruction syndrome or non-infectious pneumonitis, for serious prior toxicities recommended discussion with Amgen medical monitor).
11. Life expectancy of greater than 6 weeks per investigator's judgement at time of screening.

Phase 1b Key Exclusion Criteria:

1. Known allergy to any of the drugs used in the study (Subjects who have had a previous allergy to PEG-asparaginase and if able, may receive Erwinia asparaginase at the investigator's discretion)
2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
3. Left ventricular fractional shortening \< 30%
4. History of ≥ Grade 2 pancreatitis
5. Active graft-versus-host disease requiring systemic treatment
6. Positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment
7. Down Syndrome
8. Prior therapy restrictions:

   * Subjects must have completed therapy with granulocyte-colony stimulating factor (G-CSF) or other myeloid growth factors at least 7 days before study treatment initiation, or at least 14 days before study treatment initiation, if pegylated myeloid growth factors were administered.
   * Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
   * Subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before study treatment initiation.
   * At least 3 antibody half-lives must have elapsed since the last dose of monoclonal antibody (e.g., 66 days for rituximab and 69 days for epratuzumab) before subjects may initiate study treatment.
   * Subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation.
9. Hepatitis B infection with positive hepatitis B DNA

Phase 2 Exclusion Criteria:

1. Prior treatment with carfilzomib.
2. Intolerance, hypersensitivity, or inability to receive any of the chemotherapy components of the VXLD regimen. An exception is allowed for allergy to asparaginase products if Erwinia asparaginase is unable to be administered,
3. Autologous HSCT within 6 weeks prior to start of study treatment.
4. Allogeneic HSCT within 3 months prior to start of study treatment.
5. Active GVHD requiring systemic immune suppression.
6. Less than 30 days from discontinuation of immune suppressive therapy administered for the treatment of acute or chronic GVHD.
7. Isolated extramedullary relapse.
8. Positive bacterial or fungal infection within 14 days of enrollment (except for documented line infection, line has been removed, and blood culture after line removal is negative for 5 days prior to first dose of induction therapy). Antibiotics may be administered for prophylaxis as per institutional standards up to and after enrollment.
9. Subjects with less than 3 antibody half-lives since the last dose of monoclonal antibody (eg, 66 days for rituximab, 69 days for epratuzumab, inotuzumab for 36 days), prior to first dose of investigational product must be discussed with the Amgen medical monitor and may be allowed to enroll based on extent of disease or evidence of rapidly rising peripheral or bone marrow blast counts.
10. Cell-based immunotherapy (eg, donor leucocyte infusion, CAR-T cells, tumor vaccines) within 42 days prior to first dose of investigational product. If the Amgen medical monitor agrees, an exception may be granted to the 42-day requirement for subjects with rapidly rising peripheral or bone marrow blast counts.
11. Down's syndrome.
12. Presence of another active cancer.
13. History of grade greater than or equal to 2 pancreatitis within 6 months to screening.
14. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 4.03 grade 1 or to levels dictated in the eligibility criteria apart from alopecia or toxicities from prior anticancer therapy that are considered irreversible and do not trigger another exclusion criterion (defined as having been present and stable for greater than 4 weeks).
15. Antitumor therapy (chemotherapy, investigational agents, molecular-targeted therapy) within 7 days of day 1 of induction. Exception: hydroxyurea to control peripheral blood leukemic cell counts is allowed until start of investigational product.
16. Active viral infection, including but not limited to cytomegalovirus (CMV), Hepatitis B infection with positive serum hepatitis surface antigen or hepatitis B DNA, HIV, Hepatitis C with detectable hepatitis C RNA. Subjects who have previously received a stem cell transplant must be screened for CMV infection, unless both subject and donor are known to be CMV negative.
17. Currently receiving treatment in another investigational device or product study, or less than 14 days since ending treatment on another investigational device or product study.
18. Uncontrolled arrhythmias or screening ECG with corrected QT interval (QTc) of greater than 470 msec.
19. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
20. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
21. Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
22. Female subjects of childbearing potential with a positive pregnancy test assessed at Screening by a serum or urine pregnancy test.
23. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with spermicide during treatment and for an additional 6 months after the last dose of any study treatment, even if they have undergone a successful vasectomy.
24. Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom with spermicide during treatment, for duration of pregnancy, and for an additional 6 months after the last dose of any study treatment.
25. Male subjects unwilling to abstain from donating semen or sperm during treatment and for an additional 6 months after the last dose of any study treatment.
26. Known allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib; for a complete listing of Captisol-enabled drugs, see the Ligand Pharmaceuticals, Inc. website).

Primary outcomes:
measure: Phase 1b: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 30 days after the last dose of study treatment; maximum duration of treatment was 8 weeks
measure: Phase 1b: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
timeFrame: Up to approximately 35 days
measure: Phase 2: Percentage of Participants With Complete Remission (CR) After Induction Therapy
timeFrame: Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [Day 36 to Day 50 for infants])
Secondary outcomes:
measure: Phase 1b: Maximum Concentration (Cmax) of Carfilzomib Alone and in Combination
timeFrame: Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15 minutes (m) after the start of infusion, immediately (within 2m) before the end of infusion (EOI), EOI, 10m, 30m, 1 hour (h), 2 h, and 4h post-dose
measure: Phase 1b: Area Under the Curve (AUC) From Time 0 to the Last Quantifiable Timepoint (AUClast) of Carfilzomib
timeFrame: Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15m after the start of infusion, immediately (within 2m) before the EOI, EOI, 10m, 30m, 1h, 2 h, and 4h post-dose
measure: Phase 1b: AUC From Time 0 to Infinity (AUCinf) of Carfilzomib
timeFrame: Lead-in Cycle Day 1 (7-day cycle) and Induction Cycle Day 8 (28-day cycle): pre-dose, 15m after the start of infusion, immediately (within 2m) before the EOI, EOI, 10m, 30m, 1h, 2 h, and 4h post-dose
measure: Phase 1b: Percentage of Participants Who Achieved a Combined CR and CR Without Platelet Recovery (CRp) at the End of Induction Cycle
timeFrame: Up to approximately Day 29 of Induction Cycle (28-days cycle, assessment on Day 29)
measure: Phase 1b: Percentage of Participants Achieving Minimal Residual Disease (MRD) Status of <10-³ and <10-⁴ Lymphoblasts at the End of Induction Cycle
timeFrame: Up to approximately Day 29 of Induction Cycle (28-days cycle, assessment on Day29)
measure: Phase 2: Number of Participants Who Experienced TEAEs
timeFrame: From first dose up to 30 days after the last dose of study treatment; maximum duration of treatment was 8 weeks
measure: Phase 2: Percentage of Participants With CR With Incomplete Hematologic Recovery (CRi) After Induction Therapy or Better Remission Status
timeFrame: Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
measure: Phase 2: Event Free Survival (EFS)
timeFrame: Up to approximately 2 years
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Phase 2: Duration of Remission (DOR)
timeFrame: Up to approximately 2 years
measure: Phase 2: Percentage of Participants Achieving MRD Status of <10-³ and <10-⁴ Cells in Participants With CR After Induction Therapy
timeFrame: Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
measure: Phase 2: Percentage of Participants Achieving MRD Status of <10-³ and <10-⁴ Cells in Participants With CRi or Better Status After Induction Therapy
timeFrame: Up to Day 50 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
measure: Phase 2: Percentage of Participants Achieving MRD Status of <10-³ and <10-⁴ Cells in Participants With CRi or Better Status After Consolidation Therapy
timeFrame: Up to Day 100 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants] + 28-day cycle of consolidation therapy + + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
measure: Phase 2: Percentage of Participants Who Underwent Stem Cell Transplant or Chimeric Antigen Receptor T-cell (CAR-T) Without Intervening Relapse Following Protocol-Specified Therapy
timeFrame: Up to approximately 2 years
measure: Phase 2: Percentage of Participants With CRi or Better Remission Status After Consolidation Therapy
timeFrame: Up to Day 100 (28-day cycle of induction therapy + recovery window from Day 29 to Day 45 [up to Day 50 for infants] + 28-day cycle of consolidation therapy + + recovery window from Day 29 to Day 45 [up to Day 50 for infants])
measure: Phase 2: AUClast of Carfilzomib
timeFrame: Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
measure: Phase 2: AUCinf of Carfilzomib
timeFrame: Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
measure: Phase 2: Cmax of Carfilzomib
timeFrame: Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
measure: Phase 2: Terminal Half-life (t1/2,z) of Carfilzomib
timeFrame: Day 8 of induction cycle (28-days cycle) and Day 1 of consolidation cycle (28-days cycle)
Other outcomes:
Locations:
city: Oakland
country: United States
facility: University of California San Francisco Benioff Childrens Hospital Oakland
state: California
city: Orange
country: United States
facility: Childrens Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Childrens Healthcare of Atlanta, Egleston
state: Georgia
city: Chicago
country: United States
facility: Lurie Childrens Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Minneapolis
country: United States
facility: Childrens Hospital and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Childrens Mercy Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Childrens Hospital of New York Presbyterian
state: New York
city: Charlotte
country: United States
facility: Levine Childrens Hospital at Carolinas Medical Center d/b/a Atrium Health
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Saint Judes Childrens Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Childrens Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Childrens Hospital West Tower
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center Primary Childrens Medical Center
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Medicine Childrens
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Aleman
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Buenos Aires
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: Randwick
country: Australia
facility: Sydney Childrens Hospital
state: New South Wales
city: Westmead
country: Australia
facility: The Childrens Hospital at Westmead
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Childrens Hospital
state: Queensland
city: Parkville
country: Australia
facility: The Royal Childrens Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Perth Childrens Hospital
state: Western Australia
city: Wien
country: Austria
facility: St Anna Kinderspital
city: Salvador
country: Brazil
facility: Hospital São Rafael - IDOR
state: Bahia
city: Brasília
country: Brazil
facility: Hospital da Crianca de Brasília
state: Distrito Federal
city: Curitba
country: Brazil
facility: Liga Paranaense do Combate ao Cancer - Hospital Erasto Gaertner
state: Paraná
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe
state: Paraná
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital da Crianca Santo Antonio Irmandade Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundacao Pio 12 Hospital de Amor de Barretos
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Itaci Instituto de Tratamento do Cancer Infantil
state: São Paulo
city: São Paulo
country: Brazil
facility: Beneficencia Portuguesa de Sao Paulo
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna-ISUL EAD
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Santiago de Chile
country: Chile
facility: Hospital Luis Calvo Mackenna
city: Santiago
country: Chile
facility: Hospital Roberto del Rio
city: Valledupar
country: Colombia
facility: Sociedad de Oncologia y Hematologia del Cesar
state: Cesar
city: Cali
country: Colombia
facility: Clinica Imbanaco S.A.S
state: Valle Del Cauca
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Kobenhavn O
country: Denmark
facility: University Hospital Rigshospitalet
city: Bordeaux Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Pellegrin
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille
city: Paris
country: France
facility: Hopital Armand Trousseau
city: Paris
country: France
facility: Hopital Robert Debre
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital des enfants
city: Vandoeuvre les Nancy Cedex
country: France
facility: Centre Hospitalier Universitaire de Nancy - Hopital Enfants de Brabois
city: Athens
country: Greece
facility: Agia Sofia Children Hospital
city: Goudi
country: Greece
facility: Agia Sofia Children Hospital
city: Goudi
country: Greece
facility: General Children Hospital Panagioti and Aglaias Kyriakou
city: Patra
country: Greece
facility: General University Hospital of Patras Panagia i Voithia
city: Thessaloniki
country: Greece
facility: Ippokrateio General Hospital of Thessaloniki
city: Kowloon Bay
country: Hong Kong
facility: Hong Kong Childrens Hospital
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Bari
country: Italy
facility: Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele Presidio Ospedaliero G Rodolico
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Monza (MB)
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza Torino Ospedale Infantile Regina Margherita
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Yangsan-si, Gyeongsangnam-do
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Mexico
country: Mexico
facility: BRCR Global Mexico
state: Distrito Federal
city: Mexico
country: Mexico
facility: Instituto Nacional de Pediatria
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: BRCR Global Mexico
state: Jalisco
city: Puebla
country: Mexico
facility: BRCR Global Mexico
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum voor Kinderoncologie
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Rikshospitalet
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Lodz
country: Poland
facility: CSK Uniwersytetu Medycznego w Lodzi Uniwersyteckie Centrum Pediatrii im Marii Konopnickiej
city: Lublin
country: Poland
facility: Uniwersytecki szpital dzieciecy
city: Warszawa
country: Poland
facility: Uck wum dzieciecy szpital kliniczny im jozefa polikarpa brudzinskiego
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wroclawiu
city: Zabrze
country: Poland
facility: SPSK nr 1 im Prof Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego w Katowicach
city: Coimbra
country: Portugal
facility: Centro Hospitalar Universitario de Coimbra
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii Louis Turcanu Timisoara
city: Moscow
country: Russian Federation
facility: FSBI N N Blokhin Russian Oncology Research Center Ministry of Health of Russian Federation
city: Moscow
country: Russian Federation
facility: FSBI FSCC of pediatric hematology, oncology and immunology n a Dmitry Rogachev
city: Saint Petersburg
country: Russian Federation
facility: SBEI of HPE Saint Petersburg State Medical University na academic I P Pavlov of MoH of RF
city: Riyadh
country: Saudi Arabia
facility: King Fahad Medical City
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: KK Womens and Childrens Hospital
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Cataluña
city: Madrid
country: Spain
facility: Hospital Universitario Infantil Niño Jesus
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital Taipei Branch
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Antalya
country: Turkey
facility: Medical Park Antalya Hastanesi
city: Bursa
country: Turkey
facility: Bursa Uludag Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Medical Park Bahcelievler Hastanesi
city: Istanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi Mustafa Eraslan ve Fevzi Mercan Cocuk Hastanesi
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: