Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Study Details
Study Description
Brief Summary
This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- To compare disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse B-cell acute lymphoblastic leukemia (B-ALL) patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization) as a part of a treatment regimen prior to allogeneic bone marrow transplantation. (Closed to enrollment effective September 18, 2019)
- To compare the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization). (Closed to enrollment effective September 30, 2019)
SECONDARY OBJECTIVES:
- To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization). (Closed to enrollment effective September 18, 2019) II. To compare OS of LR relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization).
EXPLORATORY OBJECTIVES:
-
To compare the rates of minimal residual disease (MRD) >= 0.01% at the end of block 2 and block 3 for HR and IR relapse B-ALL patients in HR/IR randomization.
-
To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD < 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab.
-
To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD).
-
To evaluate blinatumomab pharmacokinetics (PK) and explore exposure-response relationships for measures of safety and effectiveness.
OUTLINE:
All patients receive Block 1 over 4 weeks.
BLOCK 1: Patients receive dexamethasone orally (PO) twice daily (BID) or intravenously (IV) on days 1-5 and 15-19; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 3 and 17; mitoxantrone hydrochloride IV over 15-30 minutes on days 1-2, and methotrexate intrathecally (IT) on day 1. Patients with central nervous system (CNS) 1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 (including isolated CNS relapse) also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8, 15, and 22. High risk and intermediate risk patients are then assigned to randomization R1. Low risk patients are assigned to randomization R2.
RANDOMIZATION R1 (HR and IR patients): Patients are randomized to 1 of 2 treatment arms. Effective 09/18/2019, HR/IR patients not yet randomized are not eligible for post-Induction therapy on AALL1331 and will be removed from protocol therapy. Patients receiving therapy on Arm A prior to Amendment #10A who have not yet received day 22 treatment on Block 3 will be offered the opportunity to cross over to Arm B to receive blinatumomab.
ARM A: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the Block 2.
ARM B: Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the first block of blinatumomab.
RANDOMIZATION R2 (LR patients): LR patients are randomized to 1 of 2 treatment arms.
ARM C: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance. CNS3 patients receive chemoradiation post-Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2.
ARM D: Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance. CNS3 patients receive chemoradiation post Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2.
BLOCK 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; methotrexate IV over 36 hours on day 8; leucovorin calcium IV or PO on days 10-11; pegaspargase IV over 1-2 hours on day 9 or 10; cyclophosphamide IV over 15-30 minutes on days 15-19; and etoposide IV over 1-2 hours on days 15-19. Patients with CNS1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 22.
BLOCK 3: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9; asparaginase intramuscularly (IM) or IV over 1 hour on days 2, 4, 9, 11, and 23; methotrexate IT on day 1and IV over 36 hours on day 22; leucovorin calcium PO or IV on days 24-25. Patients with CNS1 or CNS2 also receive methotrexate IT on day 22. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 22.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 15 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 15 and 29.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 8 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 29.
BLINATUMOMAB BLOCK 3: Patients receive blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1.
CONTINUATION 1 & 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; mercaptopurine tablet PO on days 1-42; methotrexate PO on days 8, 15, 29, and 36; or; cyclophosphamide IV over 15-30 minutes on days 43 and 50; etoposide IV over 1-2 hours on days 43 and 50; thioguanine PO once daily on days 43-49; and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 44-47 and 51-54. Patients with CNS1 or CNS2 also receive methotrexate IT on days 1 and 43, methotrexate PO every 6 hours for 4 doses on day 22, leucovorin calcium PO every 6 hours for 2 doses on day 24. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 43 ; methotrexate IV over 36 hours on day 22; and leucovorin calcium IV or PO every 6 hours on days 24-25.
MAINTENANCE: Patients receive dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; vincristine sulfate IV over 1 minute on days 1, 29, and 57; mercaptopurine tablet PO on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Patients with CNS1 or CNS2 also receive methotrexate IT on day 1. Patients with CNS3 also receive methotrexate IT on day 1. Cycles repeat every 12 weeks for up to 2 years from the beginning of treatment in the absence of disease progression or unacceptable toxicity.
MAINTENANCE CHEMORADIATION (LR CNS3 PATIENTS ONLY): Following maintenance cycle 1, patients receive 1800 cGy cranial radiation; dexamethasone PO BID or IV on days 1-7 and 15-21; vincristine sulfate IV over 1 minute on days 1, 8 and 15; and pegaspargase IV over 1-2 hours on day 1. Patients then resume maintenance with cycle 2 and beyond.
After completion of study treatment, patients are followed up annually for 10 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm A (HR and IR control) Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT and IV or SC
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given IV or PO
Other Names:
Drug: Methotrexate
Given IT, IV, and PO
Other Names:
Drug: Mitoxantrone
Given IV
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Pegaspargase
Given IV
Other Names:
Other: Pharmacological Study
Correlative studies
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
Drug: Vincristine
Given IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Experimental: Arm B (HR and IR blinatumomab) Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Biological: Blinatumomab
Given IV
Other Names:
Drug: Cytarabine
Given IT and IV or SC
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Methotrexate
Given IT, IV, and PO
Other Names:
Other: Pharmacological Study
Correlative studies
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
| Active Comparator: Arm C (LR control) Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT and IV or SC
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given IV or PO
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT, IV, and PO
Other Names:
Drug: Pegaspargase
Given IV
Other Names:
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo cranial radiation therapy
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine
Given IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Experimental: Arm D (LR blinatumomab) Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance. |
Biological: Blinatumomab
Given IV
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT and IV or SC
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Leucovorin Calcium
Given IV or PO
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT, IV, and PO
Other Names:
Drug: Pegaspargase
Given IV
Other Names:
Other: Pharmacological Study
Correlative studies
Radiation: Radiation Therapy
Undergo cranial radiation therapy
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine
Given IV
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse patients [Up to 2 years from date of randomization]
DFS of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy itoto receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). DFS is calculated as the time from randomization to date of first event (treatment failure, relapse, second malignancy, remission death) or date of last contact. Two-year DFS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.
- DFS of low risk (LR) relapse patients [Up to 3 years from date of randomization]
DFS of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). DFS is calculated as the time from randomization to date of first event (relapse, second malignancy, remission death) or date of last contact. Three-year DFS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.
Secondary Outcome Measures
- Overall survival (OS) of HR and IR relapse patients [Up to 2 years from date of randomization]
OS of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Two-year OS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.
- OS of lLR relapse patients [Up to 3 years from date of randomization]
OS of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Three-year OS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.
Other Outcome Measures
- Rates of minimal residual disease (MRD) positivity (> 0.01%) [Up to 12 weeks]
The rates at the end of Block 2 and Block 3 will be calculated for the randomized arms for HR and IR relapse patients.
- Hematologic complete remission rate (for treatment failure patients not previously receiving blinatumomab) [Up to 12 weeks]
The observed rate will be calculated among patients with treatment failure who did not previously receive blinatumomab.
- MRD negativity (< 0.01%) rate (for treatment failure patients not previously receiving blinatumomab) [Up to 12 weeks]
The observed rate will be calculated among patients with treatment failure who did not previously receive blinatumomab.
- Proportion of patients that proceed to hematopoietic stem cell transplant (HSCT) after treatment with blinatumomab (for treatment failure patients not previously receiving blinatumomab) [Up to 12 weeks]
The observed rate will be calculated among patients with treatment failure who did not previously receive blinatumomab.
- Feasibility of rapid taper of immune suppression for subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD) [Up to 10 years]
The observed rate of grade III-IV aGVHD among this subset will be calculated with 95% confidence intervals and compared descriptively to target rate.
- Safety of rapid taper of immune suppression for subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no aGVHD defined as < 5% rate of treatment-related mortality (TRM) [Up to 10 years]
The observed rate of TRM among this subset will be calculated with 95% confidence intervals and compared descriptively to target rate.
- Blinatumomab pharmacokinetics (PK) [Days 2 and 14 of cycle 1]
Blinatumomab PK will be evaluated by summarizing blinatumomab steady state concentrations and systemic clearance obtained from non-compartmental analysis. In addition, a population PK approach using a non-linear mixed effect model will also be used to assess blinatumomab PK. Exposure-response analyses will be performed to explore associations among blinatumomab exposure, relevant clinical covariates and clinical measures of safety and efficacy.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles
-
No waiting period for patients who relapse while receiving standard maintenance therapy
-
Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
-
Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status
-
Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents 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
-
Stem cell transplant or rescue: patient has not had a prior stem cell transplant or rescue
-
Patient has not had prior treatment with blinatumomab
-
With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
-
Patients must have a performance status corresponding to 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
-
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:
-
1 to < 2 years: =< 0.6 mg/dL
-
2 to < 6 years: =< 0.8 mg/dL
-
6 to < 10 years: =< 1 mg/dL
-
10 to < 13 years: =< 1.2 mg/dL
-
13 to < 16 years: =< 1.5 mg/dL (males) and =< 1.4 mg/dL (females)
-
= 16 years: =< 1.7 mg/dL (males) and =< 1.4 mg/dL (females)
-
Direct bilirubin < 3.0 mg/dL
-
Shortening fraction of >= 27% by echocardiogram, or
-
Ejection fraction of >= 50% by radionuclide angiogram
-
All patients and/or their parent or legal guardian 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 with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
-
Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
-
Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
-
Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
-
Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
-
Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
-
Patients with known human immunodeficiency virus (HIV) infection
-
Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
-
Lactating females who plan to breastfeed
-
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
-
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
-
Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
-
Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
| 2 | USA Health Strada Patient Care Center | Mobile | Alabama | United States | 36604 |
| 3 | Providence Alaska Medical Center | Anchorage | Alaska | United States | 99508 |
| 4 | Banner Children's at Desert | Mesa | Arizona | United States | 85202 |
| 5 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
| 6 | Banner University Medical Center - Tucson | Tucson | Arizona | United States | 85719 |
| 7 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
| 8 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
| 9 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 10 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 11 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
| 12 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 13 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 14 | Mattel Children's Hospital UCLA | Los Angeles | California | United States | 90095 |
| 15 | Valley Children's Hospital | Madera | California | United States | 93636 |
| 16 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 17 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 18 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 19 | Lucile Packard Children's Hospital Stanford University | Palo Alto | California | United States | 94304 |
| 20 | Sutter Medical Center Sacramento | Sacramento | California | United States | 95816 |
| 21 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 22 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
| 23 | UCSF Medical Center-Mission Bay | San Francisco | California | United States | 94158 |
| 24 | Santa Barbara Cottage Hospital | Santa Barbara | California | United States | 93102 |
| 25 | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California | United States | 90502 |
| 26 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 27 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
| 28 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
| 29 | Yale University | New Haven | Connecticut | United States | 06520 |
| 30 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
| 31 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 32 | Broward Health Medical Center | Fort Lauderdale | Florida | United States | 33316 |
| 33 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
| 34 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
| 35 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
| 36 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
| 37 | Palms West Radiation Therapy | Loxahatchee Groves | Florida | United States | 33470 |
| 38 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 39 | AdventHealth Orlando | Orlando | Florida | United States | 32803 |
| 40 | Arnold Palmer Hospital for Children | Orlando | Florida | United States | 32806 |
| 41 | Nemours Children's Clinic - Pensacola | Pensacola | Florida | United States | 32504 |
| 42 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
| 43 | Tampa General Hospital | Tampa | Florida | United States | 33606 |
| 44 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
| 45 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
| 46 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
| 47 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
| 48 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
| 49 | Saint Luke's Cancer Institute - Boise | Boise | Idaho | United States | 83712 |
| 50 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
| 51 | University of Illinois | Chicago | Illinois | United States | 60612 |
| 52 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
| 53 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 54 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
| 55 | Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | United States | 60068 |
| 56 | Saint Jude Midwest Affiliate | Peoria | Illinois | United States | 61637 |
| 57 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 58 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 59 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
| 60 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 61 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 62 | Ochsner Medical Center Jefferson | New Orleans | Louisiana | United States | 70121 |
| 63 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 64 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
| 65 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 66 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 67 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 68 | Walter Reed National Military Medical Center | Bethesda | Maryland | United States | 20889-5600 |
| 69 | Tufts Children's Hospital | Boston | Massachusetts | United States | 02111 |
| 70 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 71 | UMass Memorial Medical Center - University Campus | Worcester | Massachusetts | United States | 01655 |
| 72 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 73 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 74 | Ascension Saint John Hospital | Detroit | Michigan | United States | 48236 |
| 75 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
| 76 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 77 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
| 78 | Beaumont Children's Hospital-Royal Oak | Royal Oak | Michigan | United States | 48073 |
| 79 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
| 80 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 81 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 82 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 83 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
| 84 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 85 | Mercy Hospital Saint Louis | Saint Louis | Missouri | United States | 63141 |
| 86 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
| 87 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 88 | Sunrise Hospital and Medical Center | Las Vegas | Nevada | United States | 89109 |
| 89 | Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | United States | 89135 |
| 90 | Summerlin Hospital Medical Center | Las Vegas | Nevada | United States | 89144 |
| 91 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 92 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 93 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
| 94 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
| 95 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
| 96 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
| 97 | Saint Joseph's Regional Medical Center | Paterson | New Jersey | United States | 07503 |
| 98 | Albany Medical Center | Albany | New York | United States | 12208 |
| 99 | Montefiore Medical Center - Moses Campus | Bronx | New York | United States | 10467 |
| 100 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 101 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
| 102 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
| 103 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
| 104 | Mount Sinai Hospital | New York | New York | United States | 10029 |
| 105 | NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York | United States | 10032 |
| 106 | NYP/Weill Cornell Medical Center | New York | New York | United States | 10065 |
| 107 | University of Rochester | Rochester | New York | United States | 14642 |
| 108 | Stony Brook University Medical Center | Stony Brook | New York | United States | 11794 |
| 109 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
| 110 | New York Medical College | Valhalla | New York | United States | 10595 |
| 111 | Mission Hospital | Asheville | North Carolina | United States | 28801 |
| 112 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 113 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
| 114 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
| 115 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 116 | East Carolina University | Greenville | North Carolina | United States | 27834 |
| 117 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 118 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
| 119 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 120 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
| 121 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 122 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 123 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
| 124 | ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Toledo | Ohio | United States | 43606 |
| 125 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 126 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
| 127 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 128 | Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | United States | 18103 |
| 129 | Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | United States | 18017 |
| 130 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 131 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 132 | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
| 133 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
| 134 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 135 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 136 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
| 137 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
| 138 | T C Thompson Children's Hospital | Chattanooga | Tennessee | United States | 37403 |
| 139 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
| 140 | The Children's Hospital at TriStar Centennial | Nashville | Tennessee | United States | 37203 |
| 141 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 142 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
| 143 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
| 144 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 145 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
| 146 | El Paso Children's Hospital | El Paso | Texas | United States | 79905 |
| 147 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 148 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
| 149 | Covenant Children's Hospital | Lubbock | Texas | United States | 79410 |
| 150 | Children's Hospital of San Antonio | San Antonio | Texas | United States | 78207 |
| 151 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
| 152 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 153 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
| 154 | University of Virginia Cancer Center | Charlottesville | Virginia | United States | 22908 |
| 155 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
| 156 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
| 157 | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | United States | 23298 |
| 158 | Carilion Children's | Roanoke | Virginia | United States | 24014 |
| 159 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 160 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
| 161 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431 |
| 162 | West Virginia University Charleston Division | Charleston | West Virginia | United States | 25304 |
| 163 | West Virginia University Healthcare | Morgantown | West Virginia | United States | 26506 |
| 164 | Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | United States | 54301 |
| 165 | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | United States | 54449 |
| 166 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 167 | Princess Margaret Hospital for Children | Perth | Western Australia | Australia | 6008 |
| 168 | Perth Children's Hospital | Perth | Western Australia | Australia | 6009 |
| 169 | British Columbia Children's Hospital | Vancouver | British Columbia | Canada | V6H 3V4 |
| 170 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 171 | Janeway Child Health Centre | Saint John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 172 | IWK Health Centre | Halifax | Nova Scotia | Canada | B3K 6R8 |
| 173 | McMaster Children's Hospital at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8N 3Z5 |
| 174 | Kingston Health Sciences Centre | Kingston | Ontario | Canada | K7L 2V7 |
| 175 | Children's Hospital | London | Ontario | Canada | N6A 5W9 |
| 176 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
| 177 | Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 178 | The Montreal Children's Hospital of the MUHC | Montreal | Quebec | Canada | H3H 1P3 |
| 179 | Centre Hospitalier Universitaire Sainte-Justine | Montreal | Quebec | Canada | H3T 1C5 |
| 180 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
| 181 | Centre Hospitalier Universitaire de Quebec | Quebec | Canada | G1V 4G2 | |
| 182 | Starship Children's Hospital | Grafton | Auckland | New Zealand | 1145 |
| 183 | Christchurch Hospital | Christchurch | New Zealand | 8011 | |
| 184 | HIMA San Pablo Oncologic Hospital | Caguas | Puerto Rico | 00726 | |
| 185 | San Jorge Children's Hospital | San Juan | Puerto Rico | 00912 | |
| 186 | University Pediatric Hospital | San Juan | Puerto Rico | 00926 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Patrick A Brown, Children's Oncology Group
Study Documents (Full-Text)
More Information
Publications
None provided.- NCI-2014-00631
- NCI-2014-00631
- s15-00970
- COG-AALL1331
- AALL1331
- AALL1331
- U10CA180886
- U10CA098543