Liposome-encapsulated Daunorubicin-Cytarabine, Fludarabine Phosphate, Cytarabine, and Filgrastim in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

Phase 1

Completed

Conditions: Acute Myeloid Leukemia Post Cytotoxic Therapy
Secondary Acute Myeloid Leukemia
Recurrent Childhood Acute Myeloid Leukemia

Interventions: Drug: Cytarabine
Biological: Filgrastim
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Other: Pharmacological Study

Registration Number: NCT02642965

Lead Sponsor: Children's Oncology Group

Brief Summary: This phase I/II trial studies the side effects and best dose of liposome-encapsulated daunorubicin-cytarabine when given with fludarabine phosphate, cytarabine, and filgrastim and to see how well they work in treating younger patients with acute myeloid leukemia that has come back after treatment (relapsed) or is not responding to treatment (is refractory). Liposome-encapsulated daunorubicin-cytarabine is made up of two chemotherapy drugs, cytarabine and daunorubicin hydrochloride, and works to stop cancer cell growth by blocking the cells from dividing. Drugs used in chemotherapy, such as fludarabine phosphate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Filgrastim may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving liposome-encapsulated daunorubicin-cytarabine followed by fludarabine phosphate, cytarabine, and filgrastim may be a better treatment for patients with relapsed acute myeloid leukemia and may cause fewer side effects to the heart, a common effect of other chemotherapy treatments for acute myeloid leukemia.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine a recommended phase 2 dose (RP2D) and the toxicities associated with liposome-encapsulated daunorubicin-cytarabine (CPX-351) in pediatric and young adult patients with relapsed/refractory acute myeloid leukemia (AML).

II. To estimate the response rate (complete remission \[CR\] plus complete remission with partial platelet recovery \[CRp\]) after CPX-351 (cycle 1) followed by fludarabine phosphate, cytarabine, and filgrastim (FLAG) (cycle 2) in children with AML in first relapse.

SECONDARY OBJECTIVES:

I. To estimate the response rate (CR + CRp + complete remission with incomplete blood count recovery \[CRi\]) after one cycle of CPX-351.

II. To describe the pharmacokinetics of plasma cytarabine and daunorubicin after CPX-351 administration to pediatric and young adult patients with relapsed/refractory AML.

TERTIARY OBJECTIVES:

I. To describe the response in biomarkers of cardiac injury to a single cycle of CPX-351.

II. To explore the effect of CPX-351 on novel biochemical and imaging markers of cardiotoxicity, including plasma micro ribonucleic acid (RNAs) (miRNA) and myocardial deformation.

III. To explore the role of rare coding variants as risk factors for anthracycline-induced cardiomyopathy.

OUTLINE:

COURSE 1: Patients receive cytarabine intrathecally (IT) on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5. Patients without evidence of central nervous system (CNS) disease (CNS1) receive no further CNS-directed therapy in course 1. Patients with \< 5 white blood cells per microliter of blood with blast cells (CNS2) disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2.

COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours once daily (QD) on days 1-5.

After completion of study treatment, patients are followed up periodically for 12 months, and then yearly for 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Patients must have had histologic verification of AML at original diagnosis
Patient must have one of the following:
- Recurrent disease with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease.
- Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease
To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016)
- Relapsed patients
  - Patients must be in first relapse, and
  - Patients must not have received prior re-induction therapy
- Refractory patients
  - Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example
- Treatment-related AML (t-AML)
  - Patients must be previously untreated for secondary AML
To be eligible for the phase 2 efficacy phase:
- Relapse patients:
  - Patients must be in first marrow relapse, and
  - Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
Patients must have the status of CNS1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
Patients must have a performance status corresponding to an Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; Note: 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 recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, stem cell transplant or radiotherapy prior to entering this study; all prior treatment-related toxicities must have resolved to =< grade 2 prior to enrollment
Myelosuppressive chemotherapy: must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (excluding hydroxyurea)
- Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of CPX-351
Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent such as steroids, retinoids; Note: for agents that have known adverse events occurring beyond 7 days after administration (i.e. monoclonal antibodies), this period must be extended beyond the time during which acute adverse events are known to occur
Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation; Note: patients must have received =< than 13.6 Gray (Gy) prior radiation to the mediastinum
Stem cell transplant (SCT): no evidence of active graft vs. host disease for at least 4 weeks; for allogeneic SCT patients, >= 3 months must have elapsed since transplant
- Must have received no more than 1 prior autologous or allogeneic stem cell transplant.
- Patients must be off all systemic immunosuppressive therapy for at least 2 weeks, excluding hydrocortisone for physiologic cortisol replacement
Intrathecal cytotoxic therapy:
- No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone
- At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
Growth factors:
- Patients must not have received growth factors for 7 days prior to CPX-351
- Patients must not have received pegfilgrastim for 14 days prior to CPX-351
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: maximum serum creatinine 0.6 mg/dL (males and females)
- Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (males and females)
- Age 6 to < 10 years: maximum serum creatinine 1.0 mg/dL (males and females)
- Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (males and females)
- Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (males) and 1.4 mg/dL (females)
- Age >= 16 years: maximum serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
Direct bilirubin < 1.5 x upper limit of normal (ULN) for age and institution
Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x upper limit of normal (ULN) for age and institution (unless it is related to leukemic involvement)
Shortening fraction of >= 27% by echocardiogram, or
Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
Corrected QT (using Bazett's formula [QTcB]) interval < 500 msecs
Patients with seizure disorder may be enrolled if on anticonvulsants and if seizures are well controlled
Central nervous system (CNS) toxicity =< grade 2
Patients with a known history of human immunodeficiency virus (HIV) are eligible, if they meet all of the following conditions:
- No history of HIV complications with the exception of cluster of differentiation (CD)4 count < 200 cells/mm^3
- No antiretroviral therapy with overlapping toxicity such as myelosuppression
- HIV viral loads below the limit of detection
- No history of highly active antiretroviral therapy (HAART)-resistant HIV
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

Patients who have received > 450 mg/m^2 daunorubicin equivalents; patients who relapse after receiving AAML0531/AAML1031 therapy will be eligible for this study, provided they have not received any additional anthracyclines; NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:
- Doxorubicin (doxorubicin hydrochloride): 1
- Mitoxantrone: 3
- Idarubicin: 3
- Epirubicin: 0.5
Patients who are currently receiving another investigational drug
Patients receiving medications for treatment of left ventricular systolic dysfunction
Patients with any of the following diagnoses:
- Acute promyelocytic leukemia (APL)
- Down syndrome
- Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
- Wilson's disease and any other disorder of copper metabolism
- Juvenile myelomonocytic leukemia (JMML)
Patients with documented active, uncontrolled infection at the time of study entry
Patients with known active hepatitis B virus (HBV) and hepatitis C virus (HCV) infections
Patients with prior allergy to daunorubicin and/or cytarabine
Female patients who are pregnant are ineligible
Lactating females are not eligible
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of chemotherapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (CPX-351 and FLAG)	Filgrastim	COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.
Treatment (CPX-351 and FLAG)	Laboratory Biomarker Analysis	COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.
Treatment (CPX-351 and FLAG)	Liposome-encapsulated Daunorubicin-Cytarabine	COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.
Treatment (CPX-351 and FLAG)	Pharmacological Study	COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.
Treatment (CPX-351 and FLAG)	Cytarabine	COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.
Treatment (CPX-351 and FLAG)	Fludarabine Phosphate	COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 7 days prior to day 1 of course 2, and liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive additional 4-6 doses of cytarabine IT twice weekly starting 48 hours after the third dose of liposome-encapsulated daunorubicin-cytarabine until CNS is clear at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2. COURSE 2: Patients receive filgrastim on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours QD on days 1-5.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Dose-limiting Toxicity	28 days	Number of patients in the dose-finding phase with a dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Percentage of Responders (Complete Response or Complete Remission With Partial Platelet Recovery) After up to 2 Cycles	Up to 8 weeks	Best response (complete response or complete remission with partial platelet recovery) after up to 2 cycles of therapy, where response is assessed using the revised Acute Myeloid Leukemia International Working Group Criteria. Percentage of responders is calculated using the methods of Jung and Kim. 90% confidence interval is determined using the methods of Koyama and Chen.

Secondary Outcome Measures

Name	Time	Method
Percentage of Responders (Complete Response or Complete Remission With Partial or Incomplete Platelet Recovery) After First Cycle of Therapy	Up to 4 weeks	Response (complete response or complete remission with partial or incomplete platelet recovery) after first cycle of therapy, where response is assessed using the revised Acute Myeloid Leukemia International Working Group Criteria. Percentage of responders is calculated by the total of number of patients with complete response or complete remission with partial or incomplete platelet recovery divided by the number of patients evaluable for response after the first cycle. 95% confidence interval is determined using a binomial exact method.
Liposome-encapsulated Daunorubicin Time of Maximum Concentration	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Median liposome-encapsulated daunorubicin time of maximum observed plasma concentration will be determined for patients in the dose-finding phase.
Liposome-encapsulated Daunorubicin Area Under the Curve	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Geometric mean liposome-encapsulated daunorubicin area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration will be determined for patients in the dose-finding phase.
Liposome-encapsulated Cytarabine Clearance	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Geometric mean liposome-encapsulated cytarabine clearance following IV infusion will be determined for patients in the dose-finding phase.
Liposome-encapsulated Cytarabine Area Under the Curve	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Geometric mean liposome-encapsulated cytarabine area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration will be determined for patients in the dose-finding phase.
Liposome-encapsulated Cytarabine Volume of Distribution	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Geometric mean liposome-encapsulated cytarabine volume of distribution following IV infusion will be determined for patients in the dose-finding phase.
Liposome-encapsulated Daunorubicin Volume of Distribution	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Geometric mean liposome-encapsulated daunorubicin volume of distribution following IV infusion will be determined for patients in the dose-finding phase.
Liposome-encapsulated Cytarabine Time of Maximum Concentration	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Median liposome-encapsulated cytarabine time of maximum observed plasma concentration will be determined for patients in the dose-finding phase.
Liposome-encapsulated Daunorubicin Clearance	Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1	Geometric mean liposome-encapsulated daunorubicin clearance following IV infusion will be determined for patients in the dose-finding phase.

Trial Locations

Locations (73): Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Maine Children's Cancer Program
🇺🇸
Scarborough, Maine, United States
Kingston Health Sciences Centre
🇨🇦
Kingston, Ontario, Canada
Valley Children's Hospital
🇺🇸
Madera, California, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸
Indianapolis, Indiana, United States
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Children's Hospital of San Antonio
🇺🇸
San Antonio, Texas, United States
UCSF Medical Center-Mission Bay
🇺🇸
San Francisco, California, United States
The Children's Hospital at TriStar Centennial
🇺🇸
Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Ascension Saint John Hospital
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
University of Vermont and State Agricultural College
🇺🇸
Burlington, Vermont, United States
Saint Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸
Oakland, California, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
NYU Winthrop Hospital
🇺🇸
Mineola, New York, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦
Quebec, Canada
Mission Hospital
🇺🇸
Asheville, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
University of Florida Health Science Center - Gainesville
🇺🇸
Gainesville, Florida, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
University of Wisconsin Carbone Cancer Center
🇺🇸
Madison, Wisconsin, United States
University of Rochester
🇺🇸
Rochester, New York, United States