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Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Primary Purpose

B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
L-asparaginase
doxorubicin hydrochloride
therapeutic hydrocortisone
vincristine sulfate
cytarabine
prednisone
bortezomib
pegaspargase
methotrexate
etoposide phosphate
cyclophosphamide
filgrastim
leucovorin calcium
laboratory biomarker analysis
High Dose MTX
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Adult Acute Lymphoblastic Leukemia

Eligibility Criteria

1 Year - 31 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • 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
  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Children's Hospital of Alabama
  • University of Alabama at Birmingham
  • Phoenix Childrens Hospital
  • Arkansas Children's Hospital
  • Southern California Permanente Medical Group
  • City of Hope Medical Center
  • City of Hope
  • Loma Linda University Medical Center
  • Miller Children's Hospital
  • Children's Hospital Los Angeles
  • Cedars-Sinai Medical Center
  • Children's Hospital Central California
  • Children's Hospital and Research Center at Oakland
  • Kaiser Permanente-Oakland
  • Childrens Hospital of Orange County
  • Lucile Packard Children's Hospital Stanford University
  • University of California at Davis Cancer Center
  • Rady Children's Hospital - San Diego
  • University of California San Francisco Medical Center-Parnassus
  • Children's Hospital Colorado
  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  • Connecticut Children's Medical Center
  • Yale University
  • Alfred I duPont Hospital for Children
  • Children's National Medical Center
  • Lombardi Comprehensive Cancer Center at Georgetown University
  • Broward Health Medical Center
  • Golisano Children's Hospital of Southwest Florida
  • Memorial Healthcare System - Joe DiMaggio Children's Hospital
  • Nemours Children's Clinic-Jacksonville South
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Florida Hospital
  • UF Cancer Center at Orlando Health
  • Nemours Children's Hospital
  • Nemours Children's Clinic - Pensacola
  • All Children's Hospital
  • Saint Joseph Children's Hospital of Tampa
  • Saint Mary's Hospital
  • Children's Healthcare of Atlanta - Egleston
  • Memorial University Medical Center
  • University of Hawaii Cancer Center
  • Saint Luke's Mountain States Tumor Institute
  • Lurie Children's Hospital-Chicago
  • University of Illinois
  • University of Chicago
  • Loyola University Medical Center
  • Southern Illinois University
  • Riley Hospital for Children
  • Saint Vincent Hospital and Health Services
  • Blank Children's Hospital
  • University of Iowa Hospitals and Clinics
  • University of Kentucky
  • Kosair Children's Hospital
  • Tulane University Health Sciences Center
  • Children's Hospital New Orleans
  • Ochsner Medical Center Jefferson
  • Eastern Maine Medical Center
  • Sinai Hospital of Baltimore
  • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
  • Walter Reed National Military Medical Center
  • Floating Hospital for Children at Tufts Medical Center
  • C S Mott Children's Hospital
  • Wayne State University/Karmanos Cancer Institute
  • Saint John Hospital and Medical Center
  • Michigan State University Clinical Center
  • Hurley Medical Center
  • Helen DeVos Children's Hospital at Spectrum Health
  • Bronson Methodist Hospital
  • Kalamazoo Center for Medical Studies
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • Mayo Clinic
  • University of Mississippi Medical Center
  • Columbia Regional
  • The Childrens Mercy Hospital
  • Cardinal Glennon Children's Medical Center
  • Washington University School of Medicine
  • Saint John's Mercy Medical Center
  • Children's Hospital and Medical Center of Omaha
  • University of Nebraska Medical Center
  • Nevada Cancer Research Foundation CCOP
  • Dartmouth Hitchcock Medical Center
  • Hackensack University Medical Center
  • Morristown Memorial Hospital
  • Saint Peter's University Hospital
  • UMDNJ - Robert Wood Johnson University Hospital
  • Newark Beth Israel Medical Center
  • Saint Joseph's Regional Medical Center
  • Overlook Hospital
  • University of New Mexico Cancer Center
  • University of New Mexico
  • Albany Medical Center
  • Montefiore Medical Center - Moses Campus
  • Roswell Park Cancer Institute
  • Winthrop University Hospital
  • The Steven and Alexandra Cohen Children's Medical Center of New York
  • New York University Langone Medical Center
  • Columbia University Medical Center
  • University of Rochester
  • Stony Brook University Medical Center
  • State University of New York Upstate Medical University
  • Mission Hospital-Memorial Campus
  • University of North Carolina
  • Carolinas Medical Center
  • Novant Health Presbyterian Medical Center
  • Duke University Medical Center
  • Wake Forest University Health Sciences
  • Sanford Medical Center-Fargo
  • Children's Hospital Medical Center of Akron
  • Cincinnati Children's Hospital Medical Center
  • Rainbow Babies and Childrens Hospital
  • Cleveland Clinic Foundation
  • Nationwide Children's Hospital
  • Dayton Children's Hospital
  • The Toledo Hospital/Toledo Children's Hospital
  • Mercy Children's Hospital
  • University of Oklahoma Health Sciences Center
  • Natalie Warren Bryant Cancer Center at Saint Francis
  • Legacy Emanuel Children's Hospital
  • Legacy Emanuel Hospital and Health Center
  • Oregon Health and Science University
  • Geisinger Medical Center
  • Penn State Hershey Children's Hospital
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • Rhode Island Hospital
  • Medical University of South Carolina
  • Palmetto Health Richland
  • BI-LO Charities Children's Cancer Center
  • Greenville Cancer Treatment Center
  • Sanford USD Medical Center - Sioux Falls
  • T C Thompson Children's Hospital
  • East Tennessee Childrens Hospital
  • Vanderbilt-Ingram Cancer Center
  • Texas Tech University Health Science Center-Amarillo
  • Driscoll Children's Hospital
  • Medical City Dallas Hospital
  • University of Texas Southwestern Medical Center
  • Brooke Army Medical Center
  • Cook Children's Medical Center
  • Baylor College of Medicine
  • Covenant Children's Hospital
  • Methodist Children's Hospital of South Texas
  • University of Texas Health Science Center at San Antonio
  • Primary Children's Hospital
  • University of Vermont
  • University of Virginia
  • Childrens Hospital-King's Daughters
  • Virginia Commonwealth University
  • Carilion Clinic Children's Hospital
  • Seattle Children's Hospital
  • Providence Sacred Heart Medical Center and Children's Hospital
  • Mary Bridge Children's Hospital and Health Center
  • Madigan Army Medical Center
  • West Virginia University Charleston
  • Saint Vincent Hospital
  • University of Wisconsin Hospital and Clinics
  • Midwest Children's Cancer Center
  • Princess Margaret Hospital for Children
  • British Columbia Children's Hospital
  • CancerCare Manitoba
  • Janeway Child Health Centre
  • IWK Health Centre
  • McMaster Children's Hospital at Hamilton Health Sciences
  • Chedoke-McMaster Hospitals
  • Cancer Centre of Southeastern Ontario at Kingston General Hospital
  • Children's Hospital
  • Hospital for Sick Children
  • The Montreal Children's Hospital of the MUHC
  • Centre Hospitalier Universitaire Sainte-Justine
  • Saskatoon Cancer Centre
  • San Jorge Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs

Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr

Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs

T-cell ALL (Chemotherapy)

T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy
The percentage of eligible and evaluable patients who have achieved complete response at the end Block 1 of re-induction therapy.
Event Free Survival
Percentage of patients who were event free at 4 months
Toxic Death Rate
The proportion of toxic death rate among all eligible patients.
Severe Adverse Events (SAE) Rate.
The proportion of SAE rate among all eligible patients

Secondary Outcome Measures

Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1
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
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
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 3.

Full Information

First Posted
March 31, 2009
Last Updated
November 30, 2016
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00873093
Brief Title
Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Official Title
A Phase II Pilot Trial of Bortezomib (PS-341, Velcade) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Lymphoblastic Lymphoma, T-cell Adult Acute Lymphoblastic Leukemia, T-cell Childhood Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
148 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Arm Type
Experimental
Arm Description
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.
Arm Title
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Arm Type
Experimental
Arm Description
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.
Arm Title
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Arm Type
Experimental
Arm Description
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.
Arm Title
T-cell ALL (Chemotherapy)
Arm Type
Experimental
Arm Description
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.
Arm Title
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
L-asparaginase
Other Intervention Name(s)
ASNase, Colaspase, Crasnitin, Elspar, L-ASP
Intervention Description
Given IM 6000 IU/m2/dose Days 2 and 9
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
ADM, ADR, Adria
Intervention Description
Given IV 60 mg/m2/dose on Day 1
Intervention Type
Drug
Intervention Name(s)
therapeutic hydrocortisone
Other Intervention Name(s)
Aeroseb-HC, Barseb HC, Cetacort, Cort-Dome, Cortef
Intervention Description
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injection
Intervention Description
Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
DeCortin, Deltra
Intervention Description
Given PO or IV 40 mg/m2/day on Days 1-28
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8
Intervention Type
Drug
Intervention Name(s)
pegaspargase
Other Intervention Name(s)
L-asparaginase with polyethylene glycol, Oncaspar, PEG-ASP, PEG-L-asparaginase
Intervention Description
Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
amethopterin, Folex, methylaminopterin, Mexate, MTX
Intervention Description
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22
Intervention Type
Drug
Intervention Name(s)
etoposide phosphate
Other Intervention Name(s)
ETOP, Etopophos
Intervention Description
Given IV 100 mg/m2/dose on Days 1-5
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV 440 mg/m2/dose on Days 1-5
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given IV or SC 5 micrograms/kg/dose Only on Day 6
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Other Intervention Name(s)
CF, CFR, LV
Intervention Description
Given PO or IV 15mg/m2/dose q6h x 3 doses
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
High Dose MTX
Other Intervention Name(s)
methotrexate, amethopterin, Folex, methylaminopterin, Mexate
Intervention Description
IV 5000 mg/m2/dose Block 2: Day 22
Primary Outcome Measure Information:
Title
Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy
Description
The percentage of eligible and evaluable patients who have achieved complete response at the end Block 1 of re-induction therapy.
Time Frame
The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy.
Title
Event Free Survival
Description
Percentage of patients who were event free at 4 months
Time Frame
4 months after enrollment
Title
Toxic Death Rate
Description
The proportion of toxic death rate among all eligible patients.
Time Frame
4 months
Title
Severe Adverse Events (SAE) Rate.
Description
The proportion of SAE rate among all eligible patients
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1
Description
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 1.
Time Frame
End of Block 1 (Day 36 of Block 1) of re-induction therapy
Title
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 2
Description
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 2.
Time Frame
End of Block 2 (Day 36 of Block 2) of re-induction therapy
Title
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3
Description
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 3.
Time Frame
End of Block 3 (Day 36 of Block 3) of re-induction therapy
Other Pre-specified Outcome Measures:
Title
NF-kB Activity
Description
NF-kB activity will be measured as a continuous variable (ng NF-kB/ug protein). Differences in NF-kB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range.
Time Frame
Up to 5 years
Title
Expression of Apoptotic and Cell Cycle Proteins Assessed by Using Gene and Tissue Microarrays and Immunoblots
Description
Characterized using descriptive statistics. If differences are noted between pre- and post-treatment protein expression, pairwise comparisons will be made using paired t-test or an equivalent nonparametric test. The normality assumption will be assessed on the log-transformed data prior to paired t-test evaluation.
Time Frame
Up to 5 years
Title
Change in Stem Cell Percentage
Description
Will use descriptive statistics to assess mean +/- standard deviation for stem cell percentage before and after bortezomib treatment. If there appears to be a difference in responders vs. non-responders, stem cell percentage differences between responders and non-responders will be compared using a paired t-test or equivalent nonparametric test.
Time Frame
Baseline to post-treatment with bortezomib
Title
Plasma Concentration-time Profiles
Description
Will be analyzed using descriptive statistics and will be graphically displayed by age group and stratum. PK data will be analyzed using methods such as nonlinear mixed effects modeling to estimate bortezomib clearance and volume of distribution (and the associated 95% confidence intervals) in each age group (2-11 years and 12-16 years of age).
Time Frame
Up to day 8 of block 2
Title
Pharmacokinetics (PK) of Bortezomib in Patients Receiving Multi-agent Combination Therapy.
Description
This outcome measure cannot be reported due to the data used for analysis was not collected.
Time Frame
Day 8 of blocks 1 and 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
31 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terzah Horton, MD PhD
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202-3591
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Miller Children's Hospital
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Children's Hospital Central California
City
Madera
State/Province
California
ZIP/Postal Code
93636-8762
Country
United States
Facility Name
Children's Hospital and Research Center at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609-1809
Country
United States
Facility Name
Kaiser Permanente-Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Childrens Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868-3874
Country
United States
Facility Name
Lucile Packard Children's Hospital Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California at Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Rady Children's Hospital - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of California San Francisco Medical Center-Parnassus
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Alfred I duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Lombardi Comprehensive Cancer Center at Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
Broward Health Medical Center
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33316
Country
United States
Facility Name
Golisano Children's Hospital of Southwest Florida
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33908
Country
United States
Facility Name
Memorial Healthcare System - Joe DiMaggio Children's Hospital
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Nemours Children's Clinic-Jacksonville South
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Florida Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
UF Cancer Center at Orlando Health
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Nemours Children's Clinic - Pensacola
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Saint Joseph Children's Hospital of Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Saint Mary's Hospital
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Memorial University Medical Center
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31404
Country
United States
Facility Name
University of Hawaii Cancer Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Saint Luke's Mountain States Tumor Institute
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Lurie Children's Hospital-Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Southern Illinois University
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Saint Vincent Hospital and Health Services
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Blank Children's Hospital
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Kosair Children's Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Children's Hospital New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Ochsner Medical Center Jefferson
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Eastern Maine Medical Center
City
Bangor
State/Province
Maine
ZIP/Postal Code
04401
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889-5600
Country
United States
Facility Name
Floating Hospital for Children at Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
C S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Saint John Hospital and Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Michigan State University Clinical Center
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48824-7016
Country
United States
Facility Name
Hurley Medical Center
City
Flint
State/Province
Michigan
ZIP/Postal Code
48502
Country
United States
Facility Name
Helen DeVos Children's Hospital at Spectrum Health
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
Kalamazoo Center for Medical Studies
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49008
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Columbia Regional
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65201
Country
United States
Facility Name
The Childrens Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Saint John's Mercy Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Children's Hospital and Medical Center of Omaha
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Nevada Cancer Research Foundation CCOP
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Morristown Memorial Hospital
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
Saint Peter's University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
UMDNJ - Robert Wood Johnson University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Newark Beth Israel Medical Center
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07112
Country
United States
Facility Name
Saint Joseph's Regional Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
Overlook Hospital
City
Summit
State/Province
New Jersey
ZIP/Postal Code
07902
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
The Steven and Alexandra Cohen Children's Medical Center of New York
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
State University of New York Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Mission Hospital-Memorial Campus
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Novant Health Presbyterian Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Sanford Medical Center-Fargo
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States
Facility Name
Children's Hospital Medical Center of Akron
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Rainbow Babies and Childrens Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Dayton Children's Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
The Toledo Hospital/Toledo Children's Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Mercy Children's Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Natalie Warren Bryant Cancer Center at Saint Francis
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Legacy Emanuel Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Legacy Emanuel Hospital and Health Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822-2001
Country
United States
Facility Name
Penn State Hershey Children's Hospital
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Palmetto Health Richland
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
BI-LO Charities Children's Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Greenville Cancer Treatment Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Sanford USD Medical Center - Sioux Falls
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57117-5134
Country
United States
Facility Name
T C Thompson Children's Hospital
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
East Tennessee Childrens Hospital
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37916
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Tech University Health Science Center-Amarillo
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79106
Country
United States
Facility Name
Driscoll Children's Hospital
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78411
Country
United States
Facility Name
Medical City Dallas Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Brooke Army Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Covenant Children's Hospital
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Methodist Children's Hospital of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
University of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Childrens Hospital-King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Carilion Clinic Children's Hospital
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Providence Sacred Heart Medical Center and Children's Hospital
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Mary Bridge Children's Hospital and Health Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Madigan Army Medical Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98431
Country
United States
Facility Name
West Virginia University Charleston
City
Charleston
State/Province
West Virginia
ZIP/Postal Code
25304
Country
United States
Facility Name
Saint Vincent Hospital
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Princess Margaret Hospital for Children
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
British Columbia Children's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
CancerCare Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Facility Name
Janeway Child Health Centre
City
Saint John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
IWK Health Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3J 3G9
Country
Canada
Facility Name
McMaster Children's Hospital at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Chedoke-McMaster Hospitals
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4L8
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
Children's Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
The Montreal Children's Hospital of the MUHC
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Centre Hospitalier Universitaire Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Saskatoon Cancer Centre
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada
Facility Name
San Jorge Children's Hospital
City
San Juan
ZIP/Postal Code
00912
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
30957229
Citation
Horton TM, Whitlock JA, Lu X, O'Brien MM, Borowitz MJ, Devidas M, Raetz EA, Brown PA, Carroll WL, Hunger SP. Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's Oncology Group. Br J Haematol. 2019 Jul;186(2):274-285. doi: 10.1111/bjh.15919. Epub 2019 Apr 7.
Results Reference
derived
PubMed Identifier
28419486
Citation
Hanley MJ, Mould DR, Taylor TJ, Gupta N, Suryanarayan K, Neuwirth R, Esseltine DL, Horton TM, Aplenc R, Alonzo TA, Lu X, Milton A, Venkatakrishnan K. Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients: Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age Range. J Clin Pharmacol. 2017 Sep;57(9):1183-1193. doi: 10.1002/jcph.906. Epub 2017 Apr 18.
Results Reference
derived

Learn more about this trial

Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

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