AzTrials
AzTrials

B-cell Adult Acute Lymphoblastic LeukemiaPhase 2NCT00873093

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

A Phase 2 study testing L-asparaginase, doxorubicin hydrochloride and therapeutic hydrocortisone in people with B-cell Adult Acute Lymphoblastic Leukemia and B-cell Childhood Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 171 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 31 years
What is being tested?
L-asparaginase, doxorubicin hydrochloride and therapeutic hydrocortisone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
171 sitesin 4 countries
Study dates
Mar 2009to Sep 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 31 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

171 sites in 4 countries.

171 sites in 4 countries

United States157 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • University of New Mexico

    Albuquerque, New Mexico, 87106

  • Texas Tech University Health Science Center-Amarillo

    Amarillo, Texas, 79106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mission Hospital-Memorial Campus

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Saint Luke's Mountain States Tumor Institute

    Boise, Idaho, 83712

  • Floating Hospital for Children at Tufts Medical Center

    Boston, Massachusetts, 02111

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Vermont

    Burlington, Vermont, 05401

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Charleston

    Charleston, West Virginia, 25304

  • Carolinas Medical Center

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Virginia

    Charlottesville, Virginia, 22908

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Columbia Regional

    Columbia, Missouri, 65201

  • Palmetto Health Richland

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-2001

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Saint John Hospital and Medical Center

    Detroit, Michigan, 48236

  • Southern California Permanente Medical Group

    Downey, California, 90242

  • City of Hope Medical Center

    Duarte, California, 91010

  • City of Hope

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Michigan State University Clinical Center

    East Lansing, Michigan, 48824-7016

  • Sanford Medical Center-Fargo

    Fargo, North Dakota, 58122

  • Hurley Medical Center

    Flint, Michigan, 48502

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Greenville Cancer Treatment Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Penn State Hershey Children's Hospital

    Hershey, Pennsylvania, 17033

  • Memorial Healthcare System - Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Saint Vincent Hospital and Health Services

    Indianapolis, Indiana, 46260

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville South

    Jacksonville, Florida, 32207

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Kalamazoo Center for Medical Studies

    Kalamazoo, Michigan, 49008

  • The Childrens Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's Hospital

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Kosair Children's Hospital

    Louisville, Kentucky, 40202

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Children's Hospital Central California

    Madera, California, 93636-8762

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Morristown Memorial Hospital

    Morristown, New Jersey, 07962

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • UMDNJ - Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06520

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • New York University Langone Medical Center

    New York, New York, 10016

  • Columbia University Medical Center

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Childrens Hospital-King's Daughters

    Norfolk, Virginia, 23507

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609-1809

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Childrens Hospital of Orange County

    Orange, California, 92868-3874

  • Florida Hospital

    Orlando, Florida, 32803

  • UF Cancer Center at Orlando Health

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Legacy Emanuel Hospital and Health Center

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Carilion Clinic Children's Hospital

    Roanoke, Virginia, 24014

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • University of California at Davis Cancer Center

    Sacramento, California, 95817

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • University of California San Francisco Medical Center-Parnassus

    San Francisco, California, 94143

  • Memorial University Medical Center

    Savannah, Georgia, 31404

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Southern Illinois University

    Springfield, Illinois, 62702

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Overlook Hospital

    Summit, New Jersey, 07902

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

  • Saint Joseph Children's Hospital of Tampa

    Tampa, Florida, 33607

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467-2490

  • The Toledo Hospital/Toledo Children's Hospital

    Toledo, Ohio, 43606

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma, 74136

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Lombardi Comprehensive Cancer Center at Georgetown University

    Washington D.C., District of Columbia, 20057

  • Saint Mary's Hospital

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada12 sites

  • IWK Health Centre

    Halifax, Nova Scotia, B3J 3G9

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Chedoke-McMaster Hospitals

    Hamilton, Ontario, L8S 4L8

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, K7L 5P9

  • Children's Hospital

    London, Ontario, N6A 5W9

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

Other trials in Australia

Puerto Rico1 site

  • San Jorge Children's Hospital

    San Juan, 00912

Other trials in Puerto Rico

About this study

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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
L-asparaginase, doxorubicin hydrochloride, therapeutic hydrocortisone, vincristine sulfate, cytarabine
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L-asparaginaseDrug

    Also called ASNase, Colaspase, Crasnitin, Elspar

    Given IM 6000 IU/m2/dose Days 2 and 9

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria

    Given IV 60 mg/m2/dose on Day 1

  • therapeutic hydrocortisoneDrug

    Also called Aeroseb-HC, Barseb HC, Cetacort, Cort-Dome

    Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22

  • vincristine sulfateDrug

    Also called liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injection

    Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given PO or IV 40 mg/m2/day on Days 1-28

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8

  • pegaspargaseDrug

    Also called L-asparaginase with polyethylene glycol, Oncaspar, PEG-ASP, PEG-L-asparaginase

    Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22

  • etoposide phosphateDrug

    Also called ETOP, Etopophos

    Given IV 100 mg/m2/dose on Days 1-5

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV 440 mg/m2/dose on Days 1-5

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given IV or SC 5 micrograms/kg/dose Only on Day 6

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given PO or IV 15mg/m2/dose q6h x 3 doses

  • laboratory biomarker analysisOther

    Correlative studies

  • High Dose MTXDrug

    Also called methotrexate, amethopterin, Folex, methylaminopterin

    IV 5000 mg/m2/dose Block 2: Day 22

Study groups in NCT00873093
Study groupRoleWhat they receive
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrsExperimentalRe-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.
Receives: Drug: L-asparaginase; Drug: doxorubicin hydrochloride; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Drug: cytarabine; Drug: prednisone; Drug: bortezomib; Drug: pegaspargase; Drug: methotrexate; Drug: etoposide phosphate; Drug: cyclophosphamide; Biological: filgrastim; Drug: leucovorin calcium; Other: laboratory biomarker analysis; Drug: High Dose MTX
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yrExperimentalRe-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.
Receives: Drug: L-asparaginase; Drug: doxorubicin hydrochloride; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Drug: cytarabine; Drug: prednisone; Drug: bortezomib; Drug: pegaspargase; Drug: methotrexate; Drug: etoposide phosphate; Drug: cyclophosphamide; Biological: filgrastim; Drug: leucovorin calcium; Other: laboratory biomarker analysis; Drug: High Dose MTX
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrsExperimentalRe-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.
Receives: Drug: L-asparaginase; Drug: doxorubicin hydrochloride; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Drug: cytarabine; Drug: prednisone; Drug: bortezomib; Drug: pegaspargase; Drug: methotrexate; Drug: etoposide phosphate; Drug: cyclophosphamide; Biological: filgrastim; Drug: leucovorin calcium; Other: laboratory biomarker analysis; Drug: High Dose MTX
T-cell ALL (Chemotherapy)ExperimentalRe-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.
Receives: Drug: L-asparaginase; Drug: doxorubicin hydrochloride; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Drug: cytarabine; Drug: prednisone; Drug: bortezomib; Drug: pegaspargase; Drug: methotrexate; Drug: etoposide phosphate; Drug: cyclophosphamide; Biological: filgrastim; Drug: leucovorin calcium; Other: laboratory biomarker analysis; Drug: High Dose MTX
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)ExperimentalRe-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.
Receives: Drug: L-asparaginase; Drug: doxorubicin hydrochloride; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Drug: cytarabine; Drug: prednisone; Drug: bortezomib; Drug: pegaspargase; Drug: methotrexate; Drug: etoposide phosphate; Drug: cyclophosphamide; Biological: filgrastim; Drug: leucovorin calcium; Other: laboratory biomarker analysis; Drug: High Dose MTX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy.

  2. Event Free Survival

    Percentage of patients who were event free at 4 months

    Measured: 4 months after enrollment

  3. Toxic Death Rate

    The proportion of toxic death rate among all eligible patients.

    Measured: 4 months

  4. Severe Adverse Events (SAE) Rate.

    The proportion of SAE rate among all eligible patients

    Measured: 4 months

Secondary outcomes (3)

  1. 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.

    Measured: End of Block 1 (Day 36 of Block 1) of re-induction therapy

  2. 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.

    Measured: End of Block 2 (Day 36 of Block 2) of re-induction therapy

  3. 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.

    Measured: End of Block 3 (Day 36 of Block 3) of re-induction therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionSep 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00873093
Sponsor's protocol ID
NCI-2011-01908
Other IDs
NCI-2011-01908, AALL07P1, AALL07P1, U10CA180886, U10CA098543
Status last verified
Nov 2016
First submitted
31 Mar 2009
Last updated
27 Jan 2017
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30957229

  • 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.

    PubMed 28419486

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing L-asparaginase, doxorubicin hydrochloride and therapeutic hydrocortisone in people with B-cell Adult Acute Lymphoblastic Leukemia and B-cell Childhood Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 171 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 171 sites in United States, Canada, Australia, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy (time frame: The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00873093, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2017.

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