Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT03213665

Collaborator

Children's Oncology Group (Other)

Enrollment

118

Locations

Arm

68.8

Anticipated Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II Pediatric MATCH trial studies how well tazemetostat works in treating patients with brain tumors, solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have come back (relapsed) or do not respond to treatment (refractory) and have EZH2, SMARCB1, or SMARCA4 gene mutations. Tazemetostat may stop the growth of tumor cells by blocking EZH2 and its relation to some of the pathways needed for cell proliferation.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignant Solid Neoplasm Ann Arbor Stage III Hodgkin Lymphoma Ann Arbor Stage III Non-Hodgkin Lymphoma Ann Arbor Stage IV Hodgkin Lymphoma Ann Arbor Stage IV Non-Hodgkin Lymphoma Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Low Grade Glioma Recurrent Ependymoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Hodgkin Lymphoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Germ Cell Tumor Recurrent Malignant Glioma Recurrent Malignant Solid Neoplasm Recurrent Medulloblastoma Recurrent Neuroblastoma Recurrent Non-Hodgkin Lymphoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Recurrent Primary Central Nervous System Neoplasm Recurrent Rhabdoid Tumor Recurrent Rhabdomyosarcoma Recurrent Soft Tissue Sarcoma Refractory Hodgkin Lymphoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Germ Cell Tumor Refractory Malignant Glioma Refractory Malignant Solid Neoplasm Refractory Medulloblastoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Osteosarcoma Refractory Peripheral Primitive Neuroectodermal Tumor Refractory Rhabdoid Tumor Refractory Soft Tissue Sarcoma Rhabdoid Tumor Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Wilms Tumor	Drug: Tazemetostat	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with tazemetostat with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphoma or histiocytic disorders that harbor gain of function mutations in EZH2, or loss of function mutations in the SWI/SNF complex subunits SMARCB1 or SMARCA4 at a dose of 520 mg/m^{2/dose twice daily for patients without any CNS
involvement or 1200 mg/m}2/dose orally twice daily for patients with CNS involvement.

SECONDARY OBJECTIVES:

To estimate the progression-free survival in pediatric patients treated with tazemetostat that harbor gain of function mutations in EZH2, or loss of function mutations in the SWI/SNF complex subunits SMARCB1 or SMARCA4.
To obtain information about the tolerability of tazemetostat in children with relapsed or refractory cancer.

EXPLORATORY OBJECTIVES:

To evaluate other biomarkers as predictors of response to tazemetostat and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to tazemetostat treatment.
To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).

OUTLINE:

Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of Tazemetostat in Patients With Tumors Harboring Alterations in EZH2 or Members of the SWI/SNF Complex

Actual Study Start Date :

Jul 24, 2017

Actual Primary Completion Date :

Mar 31, 2022

Anticipated Study Completion Date :

Apr 18, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (tazemetostat) Patients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.	Drug: Tazemetostat Given PO Other Names: E7438 EPZ-6438 EPZ6438

Arm

Intervention/Treatment

Experimental: Treatment (tazemetostat)

Patients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Tazemetostat

Given PO

Other Names:

E7438

EPZ-6438

EPZ6438

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [Up to 2 years]
ORR will be defined as complete response + partial response and assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.

Secondary Outcome Measures

Progression-free survival (PFS) [From start of subprotocol treatment to time of progression or death, whichever occurs first, assessed for up to 2 years]
PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.

Other Outcome Measures

Biomarker predictors of response to tazemetostat [Up to 2 years]
Will evaluate other biomarkers as predictors of response to tazemetostat and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to tazemetostat treatment. Will be performed and will be summarized with simple summary statistics and will be descriptive in nature.
Change in tumor genomics [Up to 2 years]
To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. Will be performed and will be summarized with simple summary statistics and will be descriptive in nature.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621C based on the presence of an actionable mutation
Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice; Note: The following do not qualify as measurable disease:
Malignant fluid collections (e.g., ascites, pleural effusions)
Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
Previously radiated lesions that have not demonstrated clear progression post radiation
Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell Infusions (with or without total body irradiation [TBI]):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion:

= 84 days after infusion and no evidence of graft versus host disease (GVHD)

Autologous stem cell infusion including boost infusion: >= 42 days
Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have had prior exposure to tazemetostat or other inhibitor(s) of EZH2
For patients with solid tumors without known bone marrow involvement:
Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
Age 1 to < 2 years: male: 0.6 mg/dL; female: 0.6 mg/dL
Age 2 to < 6 years: male: 0.8 mg/dL; female: 0.8 mg/dL
Age 6 to < 10 years: male: 1 mg/dL; female: 1 mg/dL
Age 10 to < 13 years: male: 1.2 mg/dL; female: 1.2 mg/dL
Age 13 to < 16 years: male: 1.5 mg/dL; female: 1.4 mg/dL
Age >= 16 years: male: 1.7 mg/dL; female: 1.4 mg/dL
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)
Serum albumin >= 2 g/dL
Corrected QT (QTc) interval =< 480 milliseconds
Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [V] 4.0) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
International normalized ratio (INR) =< 1.5
For subjects with CNS involvement (primary tumor or metastatic disease): Subjects must not have any active bleeding, or new intratumoral hemorrhage of more than punctate size on screening MRI or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment; female subjects of childbearing potential should agree to remain abstinent or use adequate contraceptive methods for 30 days after the last dose of tazemetostat; male subjects should agree to remain abstinent or use adequate contraceptive methods, and agree to refrain from donating sperm, and for 90 days after the last dose of tazemetostat
Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
Patients who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 are prohibited from 14 days prior to the first dose of tazemetostat to the end of the study; Note: Dexamethasone for CNS tumors or metastases, on a stable dose, is allowed
Patients who have an uncontrolled infection are not eligible
On complete blood count (CBC) differential, patients must not have any significant morphologic abnormalities concerning for myeloproliferative neoplasm (MPN)/myelodysplastic syndrome (MDS) or T- acute lymphoblastic leukemia (ALL)
Patients must not have thrombocytopenia, neutropenia, or anemia of grade >= 3 (per CTCAE 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)
Patients with a history of prior history of T-lymphoblastic lymphoma (LBL)/T-ALL
Patients with any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
Patients who have received prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Banner Children's at Desert	Mesa	Arizona	United States	85202
4	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
5	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
6	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
7	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
8	Loma Linda University Medical Center	Loma Linda	California	United States	92354
9	Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
10	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
11	Mattel Children's Hospital UCLA	Los Angeles	California	United States	90095
12	Valley Children's Hospital	Madera	California	United States	93636
13	UCSF Benioff Children's Hospital Oakland	Oakland	California	United States	94609
14	Kaiser Permanente-Oakland	Oakland	California	United States	94611
15	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
16	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
17	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
18	Children's Hospital Colorado	Aurora	Colorado	United States	80045
19	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
20	Yale University	New Haven	Connecticut	United States	06520
21	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
22	Children's National Medical Center	Washington	District of Columbia	United States	20010
23	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
24	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
25	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
26	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
27	Nicklaus Children's Hospital	Miami	Florida	United States	33155
28	AdventHealth Orlando	Orlando	Florida	United States	32803
29	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
30	Nemours Children's Hospital	Orlando	Florida	United States	32827
31	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
32	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
33	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
34	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
35	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
36	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
37	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
38	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
39	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
40	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
41	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
42	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
43	Blank Children's Hospital	Des Moines	Iowa	United States	50309
44	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
45	Norton Children's Hospital	Louisville	Kentucky	United States	40202
46	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
47	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
48	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
49	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
50	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
51	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
52	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
53	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
54	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
55	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
56	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
57	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
58	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
59	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
60	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
61	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
62	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
63	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
64	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
65	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
66	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
67	Morristown Medical Center	Morristown	New Jersey	United States	07960
68	Albany Medical Center	Albany	New York	United States	12208
69	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
70	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
71	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
72	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
73	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
74	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
75	University of Rochester	Rochester	New York	United States	14642
76	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
77	New York Medical College	Valhalla	New York	United States	10595
78	Mission Hospital	Asheville	North Carolina	United States	28801
79	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
80	Duke University Medical Center	Durham	North Carolina	United States	27710
81	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
82	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
83	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
84	Dayton Children's Hospital	Dayton	Ohio	United States	45404
85	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
86	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
87	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
88	Oregon Health and Science University	Portland	Oregon	United States	97239
89	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
90	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
91	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
92	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
93	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
94	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
95	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
96	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
97	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
98	Medical City Dallas Hospital	Dallas	Texas	United States	75230
99	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
100	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
101	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
102	M D Anderson Cancer Center	Houston	Texas	United States	77030
103	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
104	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
105	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
106	Scott and White Memorial Hospital	Temple	Texas	United States	76508
107	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
108	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
109	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
110	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
111	Seattle Children's Hospital	Seattle	Washington	United States	98105
112	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
113	Madigan Army Medical Center	Tacoma	Washington	United States	98431
114	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
115	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
116	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
117	San Jorge Children's Hospital	San Juan		Puerto Rico	00912
118	University Pediatric Hospital	San Juan		Puerto Rico	00926