MedPath

A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma

Phase 1
Active, not recruiting
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT02773030
Lead Sponsor
Celgene
Brief Summary

This is a multicenter, multi-country, open-label, Phase 1b/2a dose-escalation study consisting of two parts: dose escalation (Part 1) for CC-220 monotherapy, CC-220 in combination with DEX, CC-220 in combination with DEX and DARA, CC-220 in combination with DEX and BTZ and CC-220 in combination with DEX and CFZ; and the expansion of the RP2D (Part 2) for CC-220 monotherapy and CC-220 in combination with DEX for Relapsed Refractory Multiple Myeloma (RRMM), CC-220 in combination with DEX and BTZ, and CC-220 in combination with DEX and DARA for Newly Diagnosed Multiple Myeloma (NDMM).

Detailed Description

Subjects assigned to CC-220 monotherapy, who develop progressive disease (PD) will have the option to receive DEX in addition to CC-220 after consultation with the Medical Monitor. The dose of CC-220 will not be higher than the dose of CC-220 used in combination with dexamethasone in Cohort B that has been determined to be safe. Progressive disease must be confirmed in accordance with international myeloma working group (IMWG) criteria.

For Cohorts A and B, the starting dose level of CC-220, dose level 1, is 0.3 mg. A dose level -1, of 0.15 mg, may also be evaluated if the starting dose level of 0.3 mg for 21 days of a 28-day cycle is not tolerated. For Cohorts E and F, the starting dose level of CC-220, dose level 1, is one dose level below the maximum dose for Cohort B that has been determined to be safe by the dose escalation committee (DEC) at the start of enrollment for both cohorts. For Cohort E in addition to CC-220 and DEX, daratumumab will be administered intravenously (IV) at a 16mg/kg dose. For Cohort F in addition to CC-220 and DEX, bortezomib will be administered subcutaneous (SC) at a 1.3mg/m2 dose.

All subjects who discontinue study treatment in Part 1 or Part 2 of the study for a reason other than PD or withdrawal of consent from the study will be followed for response assessment every 28 days (every 21 days for Cohort F) until PD.

The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

The initiation of Part 2 will begin when the recommended phase 2 dose (RP2D) is established in Part 1 in either Cohort A, Cohort B, Cohort E or Cohort F. The cohorts may begin once the RP2D is determined for each cohort independently during Part 1. All expansion decisions will be determined by the DEC after review of all safety, PK, biomarker and preliminary efficacy data, as applicable. During Part 2, the Independent Expert Reviewer will review safety data and any other data deemed relevant so that subject safety is ensured.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
466
Inclusion Criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
  • Relapsed and refractory multiple myeloma (RRMM) participants must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
  • Newly diagnosed multiple myeloma (NDMM) participants must have documented diagnosis with previously untreated symptomatic multiple myeloma (MM)
  • Participants in Cohorts J1 and K are those for whom autologous stem cell transplantation is not planned for initial therapy or are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation
Read More
Exclusion Criteria
  • Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study
  • Nonsecretory multiple myeloma
  • Prior history of malignancies, other than MM and select non-invasive malignancies, unless the participant has been free of the disease for ≥ 5 years

Other protocol-defined inclusion/exclusion criteria apply

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort G1: CC-220 in combination with CFZ and DEX - Part 1CC-220Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle Intravenous (IV) CFZ (Carfilzomib)administered at a starting dose of 20 mg/m2 on C1D1; and at a dose specified by cohort dose level thereafter on days 1, 8, and 15 of each 28-day cycle. Oral DEX (Dexamethasone) on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects ≤ 75 years old, the DEX dose will be 40 mg. For subjects \> 75 years old, the DEX dose will be 20 mg
Cohort A: CC-220 Monotherapy - Part 1CC-220Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
Cohort F: CC-220 with DEX and bortezomib - Part 1CC-220Oral CC-220 at dose specified by cohort dose level from Day 1-14 of each 21-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, and 15 of each 21-day cycle. For subjects \>75 years old, oral DEX at 20 mg on Days 1, 8, and 15 of each 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m\^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, and 8 at cycle ≥9 of each 21-day cycle.
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1CC-220Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Intravenous DARA at dose 16mg/kg on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle. Once the MTD and/or RP2D is determined in Cohort E (CC-220Dd), subjects will be enrolled at a dose of Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15,and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.
Cohort D: CC-220 in combination with Dexamethasone - Part 2CC-220Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle
Cohort B: CC-220 in combination with Dexamethasone (DEX) - Part 1CC-220Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, DEX will be administered at 20 mg on Days 1, 8,15, and 22 of each 28-day cycle. Subjects who surpass the age of 75 years while on treatment may be switched to the 20 mg QD dosage based on the investigator's best judgment.
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1DaratumumabOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Intravenous DARA at dose 16mg/kg on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle. Once the MTD and/or RP2D is determined in Cohort E (CC-220Dd), subjects will be enrolled at a dose of Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15,and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.
Cohort G1: CC-220 in combination with CFZ and DEX - Part 1CarfilzomibOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle Intravenous (IV) CFZ (Carfilzomib)administered at a starting dose of 20 mg/m2 on C1D1; and at a dose specified by cohort dose level thereafter on days 1, 8, and 15 of each 28-day cycle. Oral DEX (Dexamethasone) on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects ≤ 75 years old, the DEX dose will be 40 mg. For subjects \> 75 years old, the DEX dose will be 20 mg
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1CC-220Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle. Oral DEX on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. The DEX dose will be 20 mg.
Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2CC-220Oral CC-220 at 1.0mg, 1.3mg or 1.6mg from Days 1-21 of each 28-day cycle. Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15, and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.
Cohort I: CC-220 in combination with DEX in post BCMA RRMM - Part 2CC-220Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Cohort J2: CC-220 in combination with DEX and BTZ in NDMM - Part 2CC-220Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle. Oral DEX at 20 mg/day (≤ 75 years old) or 10 mg/day (\> 75 years old) for Cycles 1 to 6 on Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-6 of each 21-day cycle.
Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2DaratumumabOral CC-220 at 1.0mg, 1.3mg or 1.6mg from Days 1-21 of each 28-day cycle. Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15, and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.
Cohort J1: CC-220 in combination with DEX and BTZ in NDMM - Part 2CC-220Oral CC-220 at 1.0mg, 1.3mg or 1.6mg administered at cycles 1 to 8 on Days 1 to 14 of each 21-day cycle and cycles ≥ 9 on Days 1 to 21 of each 28-day cycle. Oral DEX at Cycles 1 to 8, 20 mg (≤ 75 years old) or 10 mg (\> 75 years old) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle and Cycles ≥ 9, 40 mg (≤ 75 years old) or 20 mg (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-8 of each 21-day cycle.
Cohort C: CC-220 Monotherapy in RRMM - Part 2CC-220CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Cohort B: CC-220 in combination with Dexamethasone (DEX) - Part 1DexamethasoneOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, DEX will be administered at 20 mg on Days 1, 8,15, and 22 of each 28-day cycle. Subjects who surpass the age of 75 years while on treatment may be switched to the 20 mg QD dosage based on the investigator's best judgment.
Cohort D: CC-220 in combination with Dexamethasone - Part 2DexamethasoneOral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle
Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1DexamethasoneOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Intravenous DARA at dose 16mg/kg on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle. Once the MTD and/or RP2D is determined in Cohort E (CC-220Dd), subjects will be enrolled at a dose of Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15,and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.
Cohort F: CC-220 with DEX and bortezomib - Part 1BortezomibOral CC-220 at dose specified by cohort dose level from Day 1-14 of each 21-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, and 15 of each 21-day cycle. For subjects \>75 years old, oral DEX at 20 mg on Days 1, 8, and 15 of each 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m\^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, and 8 at cycle ≥9 of each 21-day cycle.
Cohort G1: CC-220 in combination with CFZ and DEX - Part 1DexamethasoneOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle Intravenous (IV) CFZ (Carfilzomib)administered at a starting dose of 20 mg/m2 on C1D1; and at a dose specified by cohort dose level thereafter on days 1, 8, and 15 of each 28-day cycle. Oral DEX (Dexamethasone) on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects ≤ 75 years old, the DEX dose will be 40 mg. For subjects \> 75 years old, the DEX dose will be 20 mg
Cohort F: CC-220 with DEX and bortezomib - Part 1DexamethasoneOral CC-220 at dose specified by cohort dose level from Day 1-14 of each 21-day cycle. Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, and 15 of each 21-day cycle. For subjects \>75 years old, oral DEX at 20 mg on Days 1, 8, and 15 of each 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m\^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, and 8 at cycle ≥9 of each 21-day cycle.
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1DexamethasoneOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle. Oral DEX on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. The DEX dose will be 20 mg.
Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1CarfilzomibOral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle. Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle. Oral DEX on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. The DEX dose will be 20 mg.
Cohort I: CC-220 in combination with DEX in post BCMA RRMM - Part 2DexamethasoneOral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Cohort J1: CC-220 in combination with DEX and BTZ in NDMM - Part 2DexamethasoneOral CC-220 at 1.0mg, 1.3mg or 1.6mg administered at cycles 1 to 8 on Days 1 to 14 of each 21-day cycle and cycles ≥ 9 on Days 1 to 21 of each 28-day cycle. Oral DEX at Cycles 1 to 8, 20 mg (≤ 75 years old) or 10 mg (\> 75 years old) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle and Cycles ≥ 9, 40 mg (≤ 75 years old) or 20 mg (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-8 of each 21-day cycle.
Cohort J1: CC-220 in combination with DEX and BTZ in NDMM - Part 2BortezomibOral CC-220 at 1.0mg, 1.3mg or 1.6mg administered at cycles 1 to 8 on Days 1 to 14 of each 21-day cycle and cycles ≥ 9 on Days 1 to 21 of each 28-day cycle. Oral DEX at Cycles 1 to 8, 20 mg (≤ 75 years old) or 10 mg (\> 75 years old) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle and Cycles ≥ 9, 40 mg (≤ 75 years old) or 20 mg (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-8 of each 21-day cycle.
Cohort J2: CC-220 in combination with DEX and BTZ in NDMM - Part 2BortezomibOral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle. Oral DEX at 20 mg/day (≤ 75 years old) or 10 mg/day (\> 75 years old) for Cycles 1 to 6 on Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-6 of each 21-day cycle.
Cohort J2: CC-220 in combination with DEX and BTZ in NDMM - Part 2DexamethasoneOral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle. Oral DEX at 20 mg/day (≤ 75 years old) or 10 mg/day (\> 75 years old) for Cycles 1 to 6 on Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle. Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-6 of each 21-day cycle.
Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2DexamethasoneOral CC-220 at 1.0mg, 1.3mg or 1.6mg from Days 1-21 of each 28-day cycle. Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15, and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.
Primary Outcome Measures
NameTimeMethod
Overall response rate (ORR) of CC-220 in combination with Dexamethasone (DEX) in Cohort DApproximately 5 years

Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2011) in CC-220 in combination with DEX

Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatmentApproximately 3 years

Establish the maximum tolerated doses (MTDs) of CC-220 monotherapy, in combination with DEX, and in combination with DEX and daratumumab (CC-220Dd), in combination with DEX and bortezomib (CC-220Vd), and in combination with DEX and carfilzomib (CC-220Kd)

Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatmentApproximately 3 years

RP2D is defined as the dose selected for phase 2 based on safety, pharmacokinetics and biomarker data from phase 1 of the study

Secondary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS)Approximately 5 years

Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first

Overall Survival (OS) in Part 2 relapsed and refractory multiple myeloma (RRMM) cohortsApproximately 5 years

Time from first dose of IP to death due to any cause

Adverse Events (AEs)Approximately 5 years

Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product

Time to Response (TTR)Approximately 5 years

Is defined as the time from the first date of dosing of IP to the first date of documented response (partial response \[PR\] or greater)

Pharmacokinetics - Maximum plasma concentration of drug (Cmax)Approximately 1 year
Overall response rate (ORR)Approximately 5 years

Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better

Duration of Response (DOR)Approximately 5 years

Is defined as Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)

Pharmacokinetics - Time to maximum plasma concentration of drug (Tmax)Approximately 1 year
Very good partial response or better rate (VGPR)Approximately 4 years

Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) for subjects who achieved VGPR or better

Pharmacokinetics - Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC[TAU])Approximately 1 year

Trial Locations

Locations (89)

Local Institution - 101

🇺🇸

Atlanta, Georgia, United States

Local Institution - 108

🇺🇸

Hackensack, New Jersey, United States

Local Institution - 115

🇺🇸

Boston, Massachusetts, United States

Local Institution - 102

🇺🇸

Scottsdale, Arizona, United States

Local Institution - 120

🇺🇸

Chicago, Illinois, United States

Local Institution - 114

🇺🇸

Boston, Massachusetts, United States

Local Institution - 106

🇺🇸

Baltimore, Maryland, United States

Local Institution - 110

🇺🇸

Boston, Massachusetts, United States

Local Institution - 140

🇺🇸

Grand Island, Nebraska, United States

Local Institution - 137

🇺🇸

Omaha, Nebraska, United States

Local Institution - 138

🇺🇸

Omaha, Nebraska, United States

Local Institution - 756

🇺🇸

Cherry Hill, New Jersey, United States

Local Institution - 122

🇺🇸

Mineola, New York, United States

Local Institution - 121

🇺🇸

New York, New York, United States

Local Institution - 109

🇺🇸

New York, New York, United States

Local Institution - 111

🇺🇸

New York, New York, United States

Local Institution - 125

🇺🇸

Rochester, New York, United States

Local Institution - 112

🇺🇸

Charlotte, North Carolina, United States

Local Institution - 117

🇺🇸

Cleveland, Ohio, United States

Local Institution - 124

🇺🇸

Columbus, Ohio, United States

Local Institution - 116

🇺🇸

Philadelphia, Pennsylvania, United States

Local Institution - 123

🇺🇸

Greenville, South Carolina, United States

Local Institution - 118

🇺🇸

Dallas, Texas, United States

Local Institution - 854

🇦🇺

Adelaide, South Australia, Australia

Local Institution - 852

🇦🇺

Box Hill, Victoria, Australia

Local Institution - 904

🇨🇦

Calgary, Alberta, Canada

Local Institution - 132

🇺🇸

Tacoma, Washington, United States

Local Institution - 903

🇨🇦

Montreal, Quebec, Canada

Local Institution - 901

🇨🇦

Vancouver, British Columbia, Canada

Local Institution - 704

🇫🇷

Lile Cedax, France

Local Institution - 701

🇫🇷

Pessac, France

Local Institution - 703

🇫🇷

Pierre Benite cedex, France

Local Institution - 702

🇫🇷

Poitiers Cedex, France

Local Institution - 603

🇩🇪

Dusseldorf, Germany

Local Institution - 605

🇩🇪

Dresden, Germany

Local Institution - 604

🇩🇪

Hamburg, Germany

Local Institution - 601

🇩🇪

Tuebingen, Germany

Local Institution - 602

🇩🇪

Heidelberg, Germany

Local Institution - 307

🇮🇹

Meldola, Italy

Local Institution - 606

🇩🇪

Wuerzburg, Germany

Local Institution - 755

🇮🇱

Tel-Aviv, Israel

Local Institution - 305

🇮🇹

Pavia, Italy

Local Institution - 303

🇮🇹

Rome, Italy

Local Institution - 808

🇯🇵

Matsuyama, Ehime, Japan

Local Institution - 809

🇯🇵

Kamogawa, Japan

Local Institution - 805

🇯🇵

Aomori, Japan

Local Institution - 813

🇯🇵

Hiroshima City, Japan

Local Institution - 802

🇯🇵

Kyoto-city, Japan

Local Institution - 810

🇯🇵

Nagoya, Japan

Local Institution - 811

🇯🇵

Nagasaki-shi, Japan

Local Institution - 801

🇯🇵

Nagoya, Japan

Local Institution - 804

🇯🇵

Osaka, Japan

Local Institution - 806

🇯🇵

Shinagawa-ku, Tokyo, Japan

Local Institution - 814

🇯🇵

Sunto-gun, Japan

Local Institution - 807

🇯🇵

Toyohashi, Japan

Local Institution - 501

🇳🇱

Rotterdam, Netherlands

Local Institution - 504

🇳🇱

Maastrich, Netherlands

Local Institution - 404

🇪🇸

Badalona (Barcelona), Spain

Local Institution - 401

🇪🇸

Barcelona, Spain

Local Institution - 502

🇳🇱

Utrecht, Netherlands

Local Institution - 405

🇪🇸

Barcelona, Spain

Local Institution - 408

🇪🇸

Madrid, Spain

Local Institution - 202

🇬🇧

Leeds, United Kingdom

Local Institution - 402

🇪🇸

Pamplona, Spain

Local Institution - 407

🇪🇸

Madrid, Spain

Local Institution - 205

🇬🇧

Birmingham, United Kingdom

Local Institution - 406

🇪🇸

Valencia, Spain

Local Institution - 201

🇬🇧

Sutton, United Kingdom

Local Institution - 204

🇬🇧

Oxford, United Kingdom

Local Institution - 203

🇬🇧

Sutton, United Kingdom

Local Institution - 815

🇯🇵

Ogaki, Japan

Local Institution - 107

🇺🇸

Little Rock, Arkansas, United States

Local Institution - 104

🇺🇸

Ann Arbor, Michigan, United States

Local Institution - 131

🇺🇸

Omaha, Nebraska, United States

Local Institution - 134

🇺🇸

Memphis, Tennessee, United States

Local Institution - 141

🇺🇸

Grand Island, Nebraska, United States

Local Institution - 139

🇺🇸

Papillion, Nebraska, United States

Local Institution - 812

🇯🇵

Isehara City, Kanagawa, Japan

Local Institution - 902

🇨🇦

Halifax, Nova Scotia, Canada

Local Institution - 751

🇮🇱

Jerusalem, Yerushalayim, Israel

Local Institution - 754

🇮🇱

Tel Hashomer, Israel

Local Institution - 803

🇯🇵

Sendai, Japan

Local Institution - 503

🇳🇱

Amsterdam, NH, Netherlands

Local Institution - 113

🇺🇸

Fairway, Kansas, United States

Local Institution - 126

🇺🇸

Seattle, Washington, United States

Local Institution - 119

🇺🇸

Salt Lake City, Utah, United States

Local Institution - 103

🇺🇸

Detroit, Michigan, United States

Local Institution - 302

🇮🇹

Reggio Emilia, Italy

Local Institution - 301

🇮🇹

Torino, Italy

© Copyright 2025. All Rights Reserved by MedPath