Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
- Conditions
- B-cell Childhood Acute Lymphoblastic LeukemiaRecurrent Adult Lymphoblastic LymphomaT-cell Adult Acute Lymphoblastic LeukemiaT-cell Childhood Acute Lymphoblastic LeukemiaRecurrent Adult Acute Lymphoblastic LeukemiaB-cell Adult Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Lymphoblastic Lymphoma
- Interventions
- Biological: filgrastimOther: laboratory biomarker analysisDrug: High Dose MTX
- Registration Number
- NCT00873093
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This pilot, phase II trial studies the side effects of giving bortezomib together with combination chemotherapy and to see how well it works in treating young patients with relapsed acute lymphoblastic leukemia or lymphoblastic lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the toxicity, second complete response (CR2) rate at the end of Block 1 therapy, and 4-month event-free survival (EFS) for pediatric and young adult patients with relapsed acute lymphoblastic leukemia (ALL) treated with bortezomib in combination with intensive re-induction chemotherapy.
II. To evaluate bortezomib pharmacokinetics (PK) in patients receiving the combination regimen.
SECONDARY OBJECTIVES:
I. To assess minimal residual disease (MRD) in bone marrow following completion of each therapy block.
II. To assess the feasibility of measuring leukemia initiating cells (LIC) in patient samples before and after chemotherapy.
III. To discover biologic pathways associated with response and drug resistance using gene and protein expression profiles at baseline and following initial exposure to chemotherapy.
IV. To determine if bortezomib inhibits lymphoblast nuclear factor (NF)-kappa (k)-B activity in leukemia patients.
OUTLINE:
REINDUCTION BLOCK 1: Patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; doxorubicin hydrochloride IV over 15 minutes on day 1; prednisone orally (PO) twice daily (BID) on days 1-28; bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11; and pegaspargase intramuscularly (IM) or IV over 1-2 hours on days 2, 8, 15, and 22. Patients with central nervous system (CNS)-negative disease (CNS1 or CNS2) also receive methotrexate IT on days 15 and 29; patients with CNS-positive disease (CNS3) receive triple intrathecal therapy (TIT) comprising methotrexate, hydrocortisone, and cytarabine IT on days 8, 15, 22, and 29. After completion of reinduction block 1, patients with ALL and M2 or M3 bone marrow proceed directly to reinduction block 2. Patients with ALL and M1 bone marrow or lymphoblastic lymphoma proceed to reinduction block 2 after blood counts recover. Patients with persistent cerebral spinal fluid (CSF) blasts after 6 doses of TIT or patients with progressive lymphoblastic lymphoma are removed from the study.
REINDUCTION BLOCK 2: Patients receive etoposide phosphate IV over 1-2 hours on days 1-5; cyclophosphamide IV over 15-30 minutes on days 1-5; bortezomib IV over 3-5 seconds on days 1, 4, and 8; filgrastim (G-CSF) subcutaneously (SC) or IV daily beginning on day 6 and continuing until blood counts recover\*; high-dose methotrexate IV over 24 hours on day 22; and leucovorin calcium PO or IV every 6 hours on days 23 and 24. Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22; patients with CNS-positive disease receive TIT on days 1 and 22. After completion of reinduction block 2, patients proceed to reinduction block 3 immediately or when blood counts recover. Patients with disease progression are removed from the study.
NOTE: \*Patients do not receive G-CSF on day 8.
REINDUCTION BLOCK 3: Patients receive cytarabine IV over 3 hours BID on days 1, 2, 8, and 9; L-asparaginase IM on days 2 and 9; and G-CSF SC or IV daily beginning on day 10 and continuing until blood counts recover.
After completion of study treatment, patients are followed every 6 months for 3 years and then annually for 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 148
-
Diagnosis
- Pre-B ALL in first early (< 36 months from diagnosis) isolated bone marrow (BM) or combined BM/extramedullary relapse; or
- T-cell ALL in first isolated BM or combined relapse; or
- T-LL in first relapse
-
Patients with leukemia must have had histologic verification of the malignancy at relapse, including immunophenotyping to confirm diagnosis
-
Patients with lymphoblastic lymphoma must have measurable disease documented by clinical, radiographic, or histologic criteria; patients must have relapsed or become refractory to conventional therapy
-
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
-
Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study
-
Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
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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
-
At least 7 days since the completion of therapy with a biologic agent or donor lymphocyte infusions (DLI); 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
-
No evidence of active graft-vs-host disease (GVHD) and >= 4 months must have elapsed; must not be receiving GVHD prophylaxis
-
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 month to < 6 months (0.4 male, 0.4 female)
- 6 months to < 1 year (0.5 male, 0.5 female)
- 1 to < 2 years (0.6 male, 0.6 female)
- 2 to < 6 years (0.8 male, 0.8 female)
- 6 to < 10 years (1 male, 1 female)
- 10 to < 13 years (1.2 male, 1.2 female)
- 13 to < 16 years (1.5 male, 1.4 female)
- >= 16 years (1.7 male, 1.4 female)
-
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
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Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN for age, unless elevation due to leukemia infiltration
-
Shortening fraction of >= 27% by echocardiogram, or
-
Ejection fraction of >= 50% by gated radionuclide study
-
No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >= 94% at sea level (> 90% if at high altitude)
-
No evidence of acute pulmonary infiltrates on chest radiograph
-
Patients with seizure disorder may be enrolled if on allowed anticonvulsants and well controlled; benzodiazepines and gabapentin are acceptable
-
Central nervous system (CNS) toxicity =< grade 2
-
Peripheral nervous system (PNS) toxicity < grade 3
-
All patients and/or their parents or legal guardians must sign a written informed consent
-
All institutional, FDA, and National Cancer Institute (NCI) requirements for human studies must be met
- Patients with Philadelphia chromosome positive ALL are not eligible unless refractory to at least one tyrosine kinase inhibitor (TKI) therapy; patients that are unable to tolerate TKI therapy due to toxicity are eligible
- Patients with mature B-cell ALL, ie, leukemia with B-cell (soluble immunoglobulin [sIg] positive and kappa or lambda restricted positivity) ALL, with French-American-British (FAB) L3 morphology and/or a myc translocation, are not eligible
- Extramedullary disease status: patients with isolated CNS disease or isolated testicular disease are not eligible
- Patients with known optic nerve and/or retinal involvement are not eligible; patients presenting with visual disturbances should have an ophthalmological exam and, if indicated, an magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
- Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible
- Cumulative prior anthracycline exposure must not exceed 400 mg/m^2
- Patients taking anticonvulsants known to activate the cytochrome p450 system, in particular anticonvulsants such as phenytoin, carbamazepine, and phenobarbital, are not eligible; benzodiazepines and gabapentin are acceptable
- Patients who have previously received bortezomib or other proteasome inhibitors are not eligible
- Patients who have a known allergy to doxorubicin, cytarabine, both etoposide and etopophos, boron, mannitol or bortezomib are not eligible
- Patients who cannot receive any asparaginase products (E. Coli, PEG-asparaginase, or Erwinia asparaginase) on this study (eg, due to prior severe pancreatitis, stroke or other toxicity) are not eligible; patients who initially receive asparaginase, but must discontinue due to toxicity, remain eligible; patients with clinically significant prior allergies to pegaspargase are eligible if Erwinia L-asparaginase can be substituted
- Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective birth control method
- Patients must not have received any prior re-induction attempts and must not have received treatment for prior extramedullary relapse; patients with primary induction failure are not eligible
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description T-cell ALL (Chemotherapy) vincristine sulfate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr vincristine sulfate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs leucovorin calcium Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) leucovorin calcium Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) vincristine sulfate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs etoposide phosphate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs therapeutic hydrocortisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs vincristine sulfate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs filgrastim Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs High Dose MTX Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs High Dose MTX Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr etoposide phosphate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr laboratory biomarker analysis Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs leucovorin calcium Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs laboratory biomarker analysis Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr High Dose MTX Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs vincristine sulfate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs filgrastim Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr therapeutic hydrocortisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr leucovorin calcium Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs therapeutic hydrocortisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs laboratory biomarker analysis Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) etoposide phosphate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr filgrastim Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs etoposide phosphate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) therapeutic hydrocortisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) High Dose MTX Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) laboratory biomarker analysis Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) laboratory biomarker analysis Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) filgrastim Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) leucovorin calcium Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) therapeutic hydrocortisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) etoposide phosphate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) filgrastim Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) High Dose MTX Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs L-asparaginase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs doxorubicin hydrochloride Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs cytarabine Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs prednisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs bortezomib Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs pegaspargase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs methotrexate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs cyclophosphamide Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr L-asparaginase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr doxorubicin hydrochloride Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr prednisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr cytarabine Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr bortezomib Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr pegaspargase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr methotrexate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr cyclophosphamide Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs L-asparaginase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs doxorubicin hydrochloride Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs cytarabine Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs prednisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs bortezomib Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs pegaspargase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs methotrexate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs cyclophosphamide Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) L-asparaginase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) doxorubicin hydrochloride Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) cytarabine Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) prednisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) bortezomib Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) pegaspargase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) methotrexate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell ALL (Chemotherapy) cyclophosphamide Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) L-asparaginase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) doxorubicin hydrochloride Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) cytarabine Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) prednisone Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) bortezomib Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) pegaspargase Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) methotrexate Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine. T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy) cyclophosphamide Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
- Primary Outcome Measures
Name Time Method Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy. The percentage of eligible and evaluable patients who have achieved complete response at the end Block 1 of re-induction therapy.
Event Free Survival 4 months after enrollment Percentage of patients who were event free at 4 months
Toxic Death Rate 4 months The proportion of toxic death rate among all eligible patients.
Severe Adverse Events (SAE) Rate. 4 months The proportion of SAE rate among all eligible patients
- Secondary Outcome Measures
Name Time Method Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1 End of Block 1 (Day 36 of Block 1) of re-induction therapy Percentage of eligible and evaluable patients with MRD \< 0.01% among those who had successful MRD determination at the end of Block 1.
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 2 End of Block 2 (Day 36 of Block 2) of re-induction therapy Percentage of eligible and evaluable patients with MRD \< 0.01% among those who had successful MRD determination at the end of Block 2.
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3 End of Block 3 (Day 36 of Block 3) of re-induction therapy Percentage of eligible and evaluable patients with MRD \< 0.01% among those who had successful MRD determination at the end of Block 3.
Trial Locations
- Locations (171)
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Saint Vincent Hospital and Health Services
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Miller Children's Hospital
🇺🇸Long Beach, California, United States
City of Hope
🇺🇸Duarte, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Memorial University Medical Center
🇺🇸Savannah, Georgia, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Saint John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Penn State Hershey Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
West Virginia University Charleston
🇺🇸Charleston, West Virginia, United States
Carilion Clinic Children's Hospital
🇺🇸Roanoke, Virginia, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Children's Hospital
🇨🇦London, Ontario, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Mayo Clinic
🇺🇸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
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Nemours Children's Clinic-Jacksonville South
🇺🇸Jacksonville, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Memorial Healthcare System - Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Lombardi Comprehensive Cancer Center at Georgetown University
🇺🇸Washington, District of Columbia, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Ochsner Medical Center Jefferson
🇺🇸New Orleans, Louisiana, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Saint Joseph Children's Hospital of Tampa
🇺🇸Tampa, Florida, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Southern Illinois University
🇺🇸Springfield, Illinois, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Columbia Regional
🇺🇸Columbia, Missouri, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
University of Rochester
🇺🇸Rochester, New York, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Mission Hospital-Memorial Campus
🇺🇸Asheville, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Mercy Children's Hospital
🇺🇸Toledo, Ohio, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Texas Tech University Health Science Center-Amarillo
🇺🇸Amarillo, Texas, United States
Chedoke-McMaster Hospitals
🇨🇦Hamilton, Ontario, Canada
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of California at Davis Cancer Center
🇺🇸Sacramento, California, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸Tulsa, Oklahoma, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Floating Hospital for Children at Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
UMDNJ - Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States