AMG 176 First in Human Trial in Participants With Relapsed or Refractory Multiple Myeloma and Participants With Relapsed or Refractory Acute Myeloid Leukemia
- Conditions
- Relapsed or Refractory Multiple MyelomaRelapsed or Refractory Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT02675452
- Lead Sponsor
- Amgen
- Brief Summary
At least one dose level of AMG 176 will achieve acceptable safety and tolerability in participants with relapsed or refractory multiple myeloma and participants with relapsed or refractory acute myeloid leukemia
- Detailed Description
This is a Phase 1, first-in-human, multicenter; non-randomized, open-label and dose-exploration study of AMG 176 administered IV in participants with relapsed or refractory multiple myeloma and participants with relapsed or refractory acute myeloid leukemia The study will be conducted in five parts.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 142
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AMG 176 - Part 1a AMG 176 Part 1a - Participants with muliple myeloma (MM) administered AMG 176 as an intravenous (IV) infusion for two-consecutive days (QD2) followed by a 5 days break. AMG 176 - Part 1b AMG 176 Part 1b - Participants with multiple myeloma (MM) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break. AMG 176 - Part 3b AMG 176 Part 3b - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break. AMG 176 - Part 3d Itraconazole Part 3d - Participants in the United States with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW), for 3 weeks, in combination with itraconazole. AMG 176 - Part 4 Azacitidine Part 4 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, either once a week (QW) followed by 6 days break, or once a day, for two-consecutive days (QD2), in combination with azacitidine. AMG 176 - Part 3a AMG 176 Part 3a - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion once a day, for two-consecutive days (QD2) followed by a 5 day break. AMG 176 - Part 3c AMG 176 Part 3c - Participants in Japan only with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW) followed by 6 days break. AMG 176 - Part 3d AMG 176 Part 3d - Participants in the United States with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, once a week (QW), for 3 weeks, in combination with itraconazole. AMG 176 - Part 4 AMG 176 Part 4 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion, either once a week (QW) followed by 6 days break, or once a day, for two-consecutive days (QD2), in combination with azacitidine. AMG 176 - Part 5 AMG 176 Part 5 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion at the maximum tolerated combination dose from Part 4, either once a week (QW) followed by 6 days break, or once a day, for two-consecutive days (QD2), in combination with azacitidine. AMG 176 - Part 5 Azacitidine Part 5 - Participants with acute myeloid leukemia (AML) administered AMG 176 as an intravenous (IV) infusion at the maximum tolerated combination dose from Part 4, either once a week (QW) followed by 6 days break, or once a day, for two-consecutive days (QD2), in combination with azacitidine.
- Primary Outcome Measures
Name Time Method MM Part 1a Pharmacokinetic (PK) parameters for AMG 176: maximum observed concentration (Cmax) 1 month on treatment Evaluate the pharmacokinetics (PK) of AMG 176 when administered as monotherapy QD2
MM Part 1a Pharmacokinetic parameters for AMG 176: half-life (t1/2) 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
MM Part 1b Incidence of DLTs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a once weekly (QW) dosing schedule
MM Part 1b Pharmacokinetic parameters for AMG 176: Cmax 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
MM Part 1b Pharmacokinetic parameters for AMG 176: CL 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
AML Part 3a Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML
Multiple Myeloma (MM) Part 1a Incidence of dose-limiting toxicities (DLTs) Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the maximum tolerated dose (MTD) for two-consecutive days per week dosing schedule (QD2)
MM Part 1a Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2
MM Part 1a Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2
MM Part 1a Pharmacokinetic parameters for AMG 176: area under the concentration-time curve (AUC) 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
MM Part 1a Pharmacokinetic parameters for AMG 176: clearance (CL) 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
MM Part 1b Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule
MM Part 1b Incidence of clinically significant changes in ECGs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule
MM Part 1a Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2
MM Part 1b Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule
Acute Myeloid Leukemia (AML) Part 3a Incidence of DLTs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML
MM Part 1a Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2
MM Part 1b Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule
MM Part 1b Pharmacokinetic parameters for AMG 176: AUC 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
AML Part 3a Incidence of clinically significant changes in ECGs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML
AML Part 3a Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML
AML Part 3b Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML
AML Part 3b Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML
AML Part 3b Incidence of clinically significant changes in ECGs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML
AML Part 3b Pharmacokinetic parameters for AMG 176: AUC 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
MM Part 1a Incidence of clinically significant changes in electrocardiograms (ECGs) Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2
MM Part 1b Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule
MM Part 1b Pharmacokinetic parameters for AMG 176: t1/2 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
AML Part 3a Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML
AML Part 3a Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML
AML Part 3a Pharmacokinetic parameters for AMG 176: t1/2 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
AML Part 3b Pharmacokinetic parameters for AMG 176: t1/2 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
AML Part 3c Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML
AML Part 3c Pharmacokinetic parameters for AMG 176: CL 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan
AML Part 3b Pharmacokinetic parameters for AMG 176: CL 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
AML Part 3a Pharmacokinetic parameters for AMG 176: Cmax 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
AML Part 3a Pharmacokinetic parameters for AMG 176: AUC 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
AML Part 3a Pharmacokinetic parameters for AMG 176: CL 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QD2
AML Part 3b Incidence of DLTs Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML
AML Part 3b Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML
AML Part 3b Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML
AML Part 3b Pharmacokinetic parameters for AMG 176: Cmax 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy QW
AML Part 3c Incidence of DLTs Up to 6 months Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML
AML Part 3c Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML
AML Part 3c Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML
AML Part 3c Incidence of clinically significant changes in ECGs Up to 6 months Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML
AML Part 3c Pharmacokinetic parameters for AMG 176: AUC 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan
AML Part 4 Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine
AML Part 4 Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine
AML Part 4 Incidence of clinically significant changes in ECGs Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 5 Incidence of clinically significant changes in vital signs Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML
AML Part 3c Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML
AML Part 4 Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: CL 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 5 Incidence of clinically significant changes in ECGs Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML
AML Part 5 Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML
AML Part 3c Pharmacokinetic parameters for AMG 176: Cmax 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan
AML Part 3c Pharmacokinetic parameters for AMG 176: t1/2 1 month on treatment Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: AUC 3 weeks on treatment Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: Cmax 3 weeks on treatment Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: CL 3 weeks on treatment Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: t1/2 3 weeks on treatment Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 4 Incidence of DLTs Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the maximum tolerated combination dose (MTCD) of AMG 176 in combination with azacitidine
AML Part 4 Incidence of clinically significant changes in clinical laboratory tests Up to 6 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine
AML Part 5 Incidence of treatment-related adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML
AML Part 5 Incidence of treatment-emergent adverse events Up to 18 months Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: CL 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2 1 month on treatment Evaluate the PK of AMG 176 and azacitidine when administered in combination
- Secondary Outcome Measures
Name Time Method MM Part 1a Time to response 6 months on treatment Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
MM Part 1a Duration of response (DOR) 6 months on treatment Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
MM Part 1b BAX and caspase 3 expression in circulating monocytes and/or circulating monocyte counts 6 months on treatment Demonstrate inactivation of MCL1 by the increase of active BAX and caspase 3 in circulating monocytes and /or the decrease of circulating monocytes in AMG 176 QW treated subjects
MM Part 1b Progression free survival (PFS) 6 months on treatment Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
MM Part 1b Time to response 6 months on treatment Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
AML Part 3a, 3b and 3c Event free survival (EFS) 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
AML Part 3a, 3b and 3c Time to response 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
MM Part 1a BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts 6 months on treatment Demonstrate inactivation of myeloid cell leukemia sequence 1 (MCL1) by the increase of active Bcl 2 associated X protein (BAX) and caspase 3 in circulating monocytes and/or the decrease of circulating monocytes in AMG 176 QD2 treated subjects
MM Part 1b Overall response (OR) according to IMWG-URC for MM subjects 6 months on treatment Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
AML Part 3d Incidence of clinically significant changes in vital signs 3 weeks on treatment Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 3d Incidence of clinically significant changes in ECGs 3 weeks on treatment Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 3d Incidence of clinically significant changes in clinical laboratory tests 3 weeks on treatment Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 5 Time to response 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
MM Part 1a Overall response (OR) according to International Myeloma Working Group uniform response criteria (IMWG-URC) for MM subjects 6 months on treatment Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
MM Part 1b Duration of response (DOR) 6 months on treatment Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM
MM Part 1a Progression-free survival (PFS) 6 months on treatment Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM
AML Part 3a, 3b and 3c Overall response (OR) according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017) 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
AML Part 4 Event free survival (EFS) 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
AML Part 4 Duration of response (DOR) 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
AML Part 5 OR according to the 2017 ELN criteria in AML subjects 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
AML Part 4 Overall response (OR) according to the 2017 ELN criteria in AML subjects 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
AML Part 3a, 3b and 3c Duration of response (DOR) 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML
AML Part 3d Incidence of treatment-emergent adverse events 3 weeks on treatment Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML
AML Part 4 Time to response 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
AML Part 5 EFS 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
AML Part 5 DOR 6 months on treatment Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML
Trial Locations
- Locations (24)
University Health Network-Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Chicago Hospital
🇺🇸Chicago, Illinois, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Universitaetsklinikum der Rheinisch-Westfaelischen Technischen Hochschule Aachen
🇩🇪Aachen, Germany
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya-shi, Aichi, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama-shi, Okayama, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
NTT Medical Center Tokyo
🇯🇵Shinagawa-ku, Tokyo, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka-shi, Fukuoka, Japan
City of Hope National Medical Center
🇺🇸Duarte, California, United States