International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones
| Registry | NCT03007147 |
|---|---|
| Status | Active not recruiting |
| Phase | Phase 3 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 352 (Actual) |
| Sponsor | Children's Oncology Group (Network); collaborators: National Cancer Institute (NCI), Universita degli Studi di Milano-Bicocca |
| Conditions | Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia |
| Interventions | Allogeneic Hematopoietic Stem Cell Transplantation, Calaspargase Pegol, Cyclophosphamide, Cytarabine, Daunorubicin Hydrochloride, Dexamethasone, Dexrazoxane Hydrochloride, Doxorubicin, Etoposide, Filgrastim, Ifosfamide, Imatinib Mesylate, Laboratory Biomarker Analysis, Leucovorin Calcium, Levoleucovorin, Mercaptopurine, Methotrexate, Methylprednisolone, Pegaspargase, Prednisolone, Questionnaire Administration, Therapeutic Hydrocortisone, Thioguanine, Vincristine Sulfate (Procedure, drug, biological, other) |
| Dates | start 2017-08-08, primary completion 2026-06-30, completion 2034-09-30 (estimated), first posted 2017-01-02, last updated 2026-10-05 |
| Locations | 226 sites in United States, Australia, Austria, Belgium, Canada, Chile, Czechia, Finland and 11 more countries |
Related Papers Related Patents Related Grants Related Experts
All trials for Acute Lymphoblastic Leukemia All trials for B Acute Lymphoblastic Leukemia All trials of Allogeneic Hematopoietic Stem Cell Transplantation All trials of Calaspargase Pegol
This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL when given with strong chemotherapy, but the combination has many side effects. This trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. The trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL", and because it is similar to Ph+ ALL, is thought it will respond well to the combination of agents used to treat Ph+ ALL.
PRIMARY OBJECTIVE:
I. To compare disease-free survival (DFS) of standard risk (SR) pediatric Philadelphia chromosome (Ph)+ acute lymphoblastic leukemia (ALL) treated with continuous imatinib mesylate (imatinib) combined with either a high-risk Children's Oncology Group (COG) ALL chemotherapy backbone or the more intensive European (Es)PhALL chemotherapy backbone.
SECONDARY OBJECTIVES:
I. To compare DFS of SR pediatric Ph+ and ABL-class fusion positive ALL patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
II. To determine the feasibility of administration of imatinib after allogeneic hematopoietic stem cell transplantation (HSCT) in high risk (HR) Ph+ ALL patients.
III. To determine event-free survival (EFS) of HR pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission and post-HSCT imatinib.
IV. To compare rates of grade 3 or higher infections in standard risk (SR) Ph+ ALL patients between the two randomized arms.
V. To evaluate EFS and overall survival (OS) of all eligible Ph+ALL patients enrolled on the study.
VI. To evaluate OS in SR Ph+ ALL patients. VII. To evaluate OS in HR Ph+ ALL patients. VIII. To evaluate EFS and OS of all eligible ABL-class fusion positive ALL patients enrolled on the study.
EXPLORATORY OBJECTIVES:
I. To describe the toxicities associated with post-HSCT administration of imatinib in HR Ph+ALL patients.
II. To evaluate the long-term toxicities in SR Ph+ ALL patients treated with chemotherapy plus imatinib (no transplant), overall and between both randomized arms.
III. To determine prognostic significance of minimal residual disease (MRD) in Ph+ ALL at various time points during therapy.
IIIa. To evaluate MRD in HR patients just prior to HSCT and then at regular intervals post-HSCT and explore the association of these measurements with long-term outcome.
IIIb. To evaluate concordance of MRD assessments made by IGH-T cell receptor (TCR) polymerase chain reaction (PCR) assay and next generation sequencing (NGS) assays.
IV. To determine and validate if IKZF1 deletions alone (IKZF1del) or with other transcription factor deletions (ie, IKZF1 plus subtype \[IKZF1plus\]) or other identified genetic lesions predict poor outcomes in Ph+/ABL-class Ph-like ALL in patients treated on AALL1631.
V. To determine the frequency and prognostic significance of p190 and p210 BCR::ABL1 fusion variants in pediatric Ph+ ALL/ABL-class Ph-like ALL.
VI. To measure adherence to oral chemotherapeutic agents (imatinib, 6-mercaptopurine and methotrexate) during the maintenance phase in SR Ph+ ALL patients.
VIa. To identify factors associated with poor adherence. VIb. To determine association between relapse risk and adherence to each oral chemotherapeutic agent (separately and combined).
VII. To measure adherence to imatinib after allogeneic HSCT in HR Ph+ ALL patients and identify factors associated with poor adherence.
VIII. To compare DFS of SR ABL-class fusion positive ALL patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
IX. Other secondary and exploratory aims described above for Ph+ ALL patients (either SR or HR), if applicable, will be evaluated in ABL-class fusion positive ALL patients.
X. Secondary and exploratory aims described above for Ph+ ALL patients (either SR or HR), if applicable and feasible, will be evaluated in the super set of Ph+ and ABL-class fusion positive ALL patients.
XI. To determine the potential therapeutic impact of major secondary events via pharmacologic inhibitor screens in existing/engineered cell models of Ph+ and ABL-class Ph-like ALL harboring secondary events and to test the in vivo activity of the most compelling candidate compounds from pilot studies using patient-derived xenograft (PDX) models established from Ph+ and ABL-class Ph-like ALL samples collected from patients treated on AALL1631.
XII. To decipher the molecular and cellular heterogeneity of chronic myelogenous leukemia (CML)-like versus typical Ph+ ALL via single-cell genomics and functional assays and investigate CML-like phenotypes via single-cell ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) sequencing to identify distinct transcriptomic and mutational profiles that will provide novel opportunities for diagnostic and therapeutic interventions.
OUTLINE:
INDUCTION IA PART 1: Patients receive induction IA according to standard of care on days 1-14.
INDUCTION IA PART 2: Patients receive imatinib mesylate orally (PO) once daily (QD) or twice daily (BID) on days 15-33, prednisolone PO twice daily (BID) or methylprednisolone intravenously (IV) on days 15-28, vincristine sulfate IV over 1 minute on days 15 and 22, daunorubicin hydrochloride IV over 1-15 minutes on days 15 and 22, and methotrexate intrathecally (IT) on day 29.
INDUCTION IB: Patients receive imatinib mesylate PO QD or BID on days 1-35, cyclophosphamide IV over 30-60 minutes on days 1 and 28, mercaptopurine PO on days 1-28, cytarabine IV or subcutaneously (SC) on days 3-6, 10-13, 17-20, and 24-27, and methotrexate IT on days 10 and 24.
POST-INDUCTION THERAPY: Patients classified as standard risk are randomized to 1 of 2 arms. Patients with high risk are assigned to Arm C.
ARM A (SR patients assigned to ARM A):
CONSOLIDATION BLOCK 1: Patients receive imatinib mesylate PO QD or BID on days 1-21, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 1, high dose methotrexate IV over 24 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 6, dexamethasone PO BID or IV on days 1-5, cyclophosphamide IV over 30-60 minutes on days 2-4, leucovorin calcium or levoleucovorin PO or IV on days 3 and 4, high dose cytarabine IV over 3 hours and pegaspargase or calaspargase pegol IV over 1-2 hours on day 5, and filgrastim SC or IV on days 7-11 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 2: Patients receive imatinib mesylate PO QD or BID on days 1-21, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 1, high dose methotrexate IV over 24 hours on day 1, dexamethasone PO BID or IV on days 1-5, vincristine sulfate IV over 1 minute on days 1 and 6, ifosfamide IV over 1 hour on days 2-4, leucovorin calcium or levoleucovorin PO or IV on days 3 and 4, dexrazoxane hydrochloride IV over 15 minutes and daunorubicin hydrochloride IV over 1-15 minutes on day 5, pegaspargase or calaspargase pegol IV over 1-2 hours on day 6, and filgrastim SC or IV on days 7-11 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 3: Patients receive imatinib mesylate PO QD or BID on days 1-21, high dose cytarabine IV over 3 hours on days 1-3, dexamethasone PO BID or IV on days 1-5, etoposide IV over 1-2 hours on days 3-5, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 5, pegaspargase or calaspargase pegol IV over 1-2 hours on day 6, and filgrastim SC or IV on days 7-11 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 1 PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-35, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 15 minutes, and doxorubicin IV over 3-15 minutes on days 8, 15, 22, and 29, and pegaspargase or calaspargase pegol IV over 1-2 hours on day 8 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 1 PART 2: Patients receive imatinib mesylate PO QD on days 36-63, cyclophosphamide IV over 30-60 minutes on day 36, thioguanine PO on days 36-49, cytarabine IV over 1-30 minutes or SC on days 38-41 and 45-48, and methotrexate IT on days 38 and 45in the absence of disease progression or unexpected toxicity.
INTERIM MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-28, methotrexate PO on days 1, 8, 15, and 22, and mercaptopurine PO on days 1-28 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 2 PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-35, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 15 minutes, and doxorubicin IV over 3-15 minutes on days 8, 15, 22, and 29, and pegaspargase or calaspargase pegol IV over 1-2 hours on day 8 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 2 PART 2: Patients receive imatinib mesylate PO QD on days 36-49, cyclophosphamide IV over 30-60 minutes on day 36, thioguanine PO on days 36-49, cytarabine IV over 1-30 minutes or SC on days 36-39 and 43-46, and methotrexate IT on days 36 and 43 in the absence of disease progression or unexpected toxicity.
MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-84, methotrexate PO once weekly (QW) and IT on days 1 and 43 of cycles 1, 2, and 3, and mercaptopurine PO on days 1-84. Cycles with imatinib mesylate and mercaptopurine repeat every 84 days for up to 104 weeks from the start of Induction IA in the absence of disease progression or unexpected toxicity.
ARM B (SR PATIENTS ASSIGNED TO ARM B):
INTERIM MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-63, vincristine sulfate IV over 1 minute and high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin calcium or levoleucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO on days 1-56, and methotrexate IT on days 1 and 29 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-28, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 15 minutes, and doxorubicin IV over 3-15 minutes on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or IM on day 4 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION PART 2: Patients receive imatinib mesylate PO QD on days 29-56, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine sulfate IV over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours on day 43 in the absence of disease progression or unexpected toxicity.
INTERIM MAINTENANCE WITH CAPIZZI METHOTREXATE: Patients receive imatinib mesylate PO QD or BID on days 1-56, vincristine sulfate IV over 1 minute and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 23 in the absence of disease progression or unexpected toxicity.
MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-84, vincristine sulfate IV over 1 minute on days 1, 29, and 57, prednisolone PO BID (or methylprednisolone IV for cycle 1 and 2) on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, methotrexate PO QW, and methotrexate IT on day 1 (and day 29 for cycle 1 and 2). Cycles repeat every 84 days for up to 104 weeks from the start of Induction IA in the absence of disease progression or unexpected toxicity.
ARM C (HR PATIENTS):
CONSOLIDATION BLOCK 1: Patients receive imatinib mesylate, methotrexate, cytarabine, therapeutic hydrocortisone, high dose methotrexate, vincristine sulfate, dexamethasone, leucovorin calcium or levoleucovorin, high dose cytarabine, and pegaspargase or calaspargase pegol as in Arm A Consolidation Block 1, and filgrastim SC or IV on day 7 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 2: Patients receive imatinib mesylate, methotrexate, cytarabine, therapeutic hydrocortisone, high dose methotrexate, dexamethasone, vincristine sulfate, ifosfamide, leucovorin calcium or levoleucovorin, dexrazoxane hydrochloride, daunorubicin hydrochloride, pegaspargase or calaspargase pegol, and filgrastim as Arm A Consolidation Block 2 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 3: Patients receive imatinib mesylate, dexamethasone, etoposide, methotrexate, cytarabine, therapeutic hydrocortisone, pegaspargase or calaspargase pegol, and filgrastim as in Arm A Consolidation Block 3, and high dose cytarabine IV over 3 hours on days 1-2 in the absence of disease progression or unexpected toxicity.
HSCT: Patients undergo HSCT on day 0. Patients who do not proceed to HSCT receive Delayed Intensification 1, Interim Maintenance, Delayed Intensification 2, and Maintenance as in Arm A.
POST-HSCT: Patients receive imatinib mesylate PO QD or BID starting on days 56-365 in the in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up every year for 3 years.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Arm A (imatinib mesylate, EsPhALL chemotherapy) | Experimental | Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Dexrazoxane Hydrochloride; Drug: Doxorubicin; Drug: Etoposide; Biological: Filgrastim; Drug: Ifosfamide; Drug: Imatinib Mesylate; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Levoleucovorin; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Drug: Prednisolone; Other: Questionnaire Administration; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Vincristine Sulfate | See Detailed Description |
| Arm B (imatinib mesylate, COG/BFM chemotherapy) | Experimental | Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Dexrazoxane Hydrochloride; Drug: Doxorubicin; Drug: Imatinib Mesylate; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Levoleucovorin; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Drug: Prednisolone; Other: Questionnaire Administration; Drug: Thioguanine; Drug: Vincristine Sulfate | See Detailed Description. |
| Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) | Experimental | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Dexrazoxane Hydrochloride; Drug: Doxorubicin; Drug: Etoposide; Biological: Filgrastim; Drug: Ifosfamide; Drug: Imatinib Mesylate; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Levoleucovorin; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Drug: Prednisolone; Other: Questionnaire Administration; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Vincristine Sulfate | See Detailed Description |
Sex: All, ages: 1 Year to 21 Years
Inclusion Criteria: * For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled * For patients who have not previously enrolled on APEC14B1 prior to enrollment on AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an MRD probe * In addition, laboratory reports detailing evidence of BCR::ABL1 fusion or ABL-class fusion must be submitted for rapid central review within 72 hours of study enrollment * >= 1 year (365 days) and =< 21 years at ALL diagnosis * Ph+ (BCR::ABL1 fusion): newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization \[WHO\] definition) with definitive evidence of BCR::ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or molecular methodologies * ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA. Methods of detection include fluorescence in-situ hybridization (\[FISH\], e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole transcriptome or panel-based RNA-sequencing (e.g. TruSight RNA Pan-Cancer Panel; Illumina, San Diego, California \[CA\], United States of America \[USA\] or similar) * Ph+ patients must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy * Ph+ patients have not received more than 14 days of multiagent Induction therapy beginning with the first dose of vinCRIStine * Ph+ patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib * ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy (Induction IA phase) * ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vinCRIStine dose * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2 * Direct bilirubin =< 2.0 mg/dL * Shortening fraction of >= 27% by echocardiogram * Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram * Corrected QT interval, QTc < 480 msec * Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis, before study enrollment * Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m\^2 or serum creatinine within normal limits based on age/gender, as follows: * 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female) * 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female) * 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female) * 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female) * 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female) * >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female) Exclusion Criteria: * Known history of chronic myelogenous leukemia (CML) * ALL developing after a previous cancer treated with cytotoxic chemotherapy * Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation * Down syndrome * Pregnancy and breast feeding * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential * Lactating females who plan to breastfeed their infants * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of treatment according to protocol * Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block * Prior treatment with dasatinib, or any TKI other than imatinib
| Facility | City | Country | Status |
|---|---|---|---|
| Children's Hospital of Alabama | Birmingham, Alabama | United States | |
| USA Health Strada Patient Care Center | Mobile, Alabama | United States | |
| Providence Alaska Medical Center | Anchorage, Alaska | United States | |
| Banner Children's at Desert | Mesa, Arizona | United States | |
| Phoenix Childrens Hospital | Phoenix, Arizona | United States | |
| Banner University Medical Center - Tucson | Tucson, Arizona | United States | |
| Arkansas Children's Hospital | Little Rock, Arkansas | United States | |
| Kaiser Permanente Downey Medical Center | Downey, California | United States | |
| City of Hope Comprehensive Cancer Center | Duarte, California | United States | |
| Loma Linda University Medical Center | Loma Linda, California | United States | |
| Miller Children's and Women's Hospital Long Beach | Long Beach, California | United States | |
| Children's Hospital Los Angeles | Los Angeles, California | United States | |
| Cedars-Sinai Medical Center | Los Angeles, California | United States | |
| Valley Children's Hospital | Madera, California | United States | |
| UCSF Benioff Children's Hospital Oakland | Oakland, California | United States | |
| Kaiser Permanente-Oakland | Oakland, California | United States | |
| Children's Hospital of Orange County | Orange, California | United States | |
| Lucile Packard Children's Hospital Stanford University | Palo Alto, California | United States | |
| University of California Davis Comprehensive Cancer Center | Sacramento, California | United States | |
| Rady Children's Hospital - San Diego | San Diego, California | United States | |
| UCSF Medical Center-Mission Bay | San Francisco, California | United States | |
| Children's Hospital Colorado | Aurora, Colorado | United States | |
| Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver, Colorado | United States | |
| Connecticut Children's Medical Center | Hartford, Connecticut | United States | |
| Yale University | New Haven, Connecticut | United States | |
| Alfred I duPont Hospital for Children | Wilmington, Delaware | United States | |
| MedStar Georgetown University Hospital | Washington D.C., District of Columbia | United States | |
| Children's National Medical Center | Washington D.C., District of Columbia | United States | |
| Broward Health Medical Center | Fort Lauderdale, Florida | United States | |
| Golisano Children's Hospital of Southwest Florida | Fort Myers, Florida | United States | |
| UF Health Cancer Institute - Gainesville | Gainesville, Florida | United States | |
| Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood, Florida | United States | |
| Nemours Children's Clinic-Jacksonville | Jacksonville, Florida | United States | |
| Palms West Radiation Therapy | Loxahatchee Groves, Florida | United States | |
| University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami, Florida | United States | |
| Nicklaus Children's Hospital | Miami, Florida | United States | |
| Miami Cancer Institute | Miami, Florida | United States | |
| AdventHealth Orlando | Orlando, Florida | United States | |
| Arnold Palmer Hospital for Children | Orlando, Florida | United States | |
| Nemours Children's Hospital | Orlando, Florida | United States | |
| Sacred Heart Hospital | Pensacola, Florida | United States | |
| Johns Hopkins All Children's Hospital | St. Petersburg, Florida | United States | |
| Tampa General Hospital | Tampa, Florida | United States | |
| Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa, Florida | United States | |
| Saint Mary's Medical Center | West Palm Beach, Florida | United States | |
| Children's Healthcare of Atlanta - Arthur M Blank Hospital | Atlanta, Georgia | United States | |
| Augusta University Medical Center | Augusta, Georgia | United States | |
| Atrium Health Navicent | Macon, Georgia | United States | |
| Memorial Health University Medical Center | Savannah, Georgia | United States | |
| Kapiolani Medical Center for Women and Children | Honolulu, Hawaii | United States | |
| Saint Luke's Cancer Institute - Boise | Boise, Idaho | United States | |
| Lurie Children's Hospital-Chicago | Chicago, Illinois | United States | |
| University of Illinois | Chicago, Illinois | United States | |
| University of Chicago Comprehensive Cancer Center | Chicago, Illinois | United States | |
| Advocate Children's Hospital-Oak Lawn | Oak Lawn, Illinois | United States | |
| Advocate Children's Hospital-Park Ridge | Park Ridge, Illinois | United States | |
| OSF Children's Hospital of Illinois | Peoria, Illinois | United States | |
| Southern Illinois University School of Medicine | Springfield, Illinois | United States | |
| Riley Hospital for Children | Indianapolis, Indiana | United States | |
| Ascension Saint Vincent Indianapolis Hospital | Indianapolis, Indiana | United States | |
| Blank Children's Hospital | Des Moines, Iowa | United States | |
| University of Iowa/Holden Comprehensive Cancer Center | Iowa City, Iowa | United States | |
| University of Kentucky/Markey Cancer Center | Lexington, Kentucky | United States | |
| Norton Children's Hospital | Louisville, Kentucky | United States | |
| Ochsner Medical Center Jefferson | New Orleans, Louisiana | United States | |
| Eastern Maine Medical Center | Bangor, Maine | United States | |
| Maine Children's Cancer Program | Scarborough, Maine | United States | |
| Sinai Hospital of Baltimore | Baltimore, Maryland | United States | |
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore, Maryland | United States | |
| Walter Reed National Military Medical Center | Bethesda, Maryland | United States | |
| Tufts Children's Hospital | Boston, Massachusetts | United States | |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts | United States | |
| Dana-Farber Cancer Institute | Boston, Massachusetts | United States | |
| UMass Memorial Medical Center - University Campus | Worcester, Massachusetts | United States | |
| C S Mott Children's Hospital | Ann Arbor, Michigan | United States | |
| Children's Hospital of Michigan | Detroit, Michigan | United States | |
| Henry Ford Health Saint John Hospital | Detroit, Michigan | United States | |
| Michigan State University | East Lansing, Michigan | United States | |
| Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital | Grand Rapids, Michigan | United States | |
| Bronson Methodist Hospital | Kalamazoo, Michigan | United States | |
| Corewell Health Children's | Royal Oak, Michigan | United States | |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota | United States | |
| University of Minnesota/Masonic Cancer Center | Minneapolis, Minnesota | United States | |
| University of Mississippi Medical Center | Jackson, Mississippi | United States | |
| University of Missouri Children's Hospital | Columbia, Missouri | United States | |
| Children's Mercy Hospitals and Clinics | Kansas City, Missouri | United States | |
| Washington University School of Medicine | St Louis, Missouri | United States | |
| Mercy Hospital Saint Louis | St Louis, Missouri | United States | |
| Children's Hospital and Medical Center of Omaha | Omaha, Nebraska | United States | |
| University of Nebraska Medical Center | Omaha, Nebraska | United States | |
| University Medical Center of Southern Nevada | Las Vegas, Nevada | United States | |
| Sunrise Hospital and Medical Center | Las Vegas, Nevada | United States | |
| Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas, Nevada | United States | |
| Summerlin Hospital Medical Center | Las Vegas, Nevada | United States | |
| Renown Regional Medical Center | Reno, Nevada | United States | |
| Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center | Lebanon, New Hampshire | United States | |
| Hackensack University Medical Center | Hackensack, New Jersey | United States | |
| Morristown Medical Center | Morristown, New Jersey | United States | |
| Jersey Shore Medical Center | Neptune City, New Jersey | United States | |
| Saint Peter's University Hospital | New Brunswick, New Jersey | United States |
126 more sites not listed.
NIH grants: U10CA180886, 2017