AzTrials
AzTrials

B-cell Childhood Acute Lymphoblastic LeukemiaPhase 3NCT00381680

Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia

A Phase 3 study testing vincristine sulfate, prednisone and doxorubicin hydrochloride in people with B-cell Childhood Acute Lymphoblastic Leukemia and L1 Childhood Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 173 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 randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 1 year to 29 years
What is being tested?
vincristine sulfate, prednisone and doxorubicin hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
275 participants
Where
173 sitesin 4 countries
Study dates
Mar 2007to Mar 2016
Phase
Phase 3
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 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis of acute lymphoblastic leukemia (ALL)
  • Bone marrow with > 25% L1 or L2 lymphoblasts (M3 marrow)
  • Patients with > 25% L3 marrow lymphoblasts and/or evidence of c-myc translocation are not eligible (considered Burkitt's or mature B-cell leukemia)
  • Intermediate-risk relapsed disease, meeting 1 of the following criteria:
  • Bone marrow relapse ≥ 36 months after initial diagnosis (defined as M3 marrow after previous remission from ALL)
  • Combined bone marrow and extramedullary (CNS* and/or testicular**) relapse ≥ 36 months after initial diagnosis
Show all 25Show fewer
  • Isolated extramedullary (CNS* and/or testicular**) relapse < 18 months after initial diagnosis
  • The following subtypes are not allowed:
  • T-lineage ALL
  • Mature B-cell (Burkitt's) leukemia (defined as L3 morphology and/or evidence of c-myc translocation)
  • Philadelphia-chromosome positive disease
  • No Down syndrome (trisomy 21)
  • Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by radionuclide angiogram
  • Bilirubin < 3.0 mg/dL
  • Not pregnant
  • Fertile patients must use effective contraception
  • No history of peripheral neuropathy >= grade 3 within the past month
  • No toxicity (i.e. peripheral neuropathy) >= grade 3 attributable to vincristine within the past month
  • At least 5 days since prior intrathecal chemotherapy
  • No prior hematopoietic stem cell or marrow transplantation
  • No prior cranial radiotherapy > 1200 cGy (for patients with CNS relapse)
  • No concurrent stem cell transplant
  • No concurrent alternative therapy
  • No concurrent itraconazole in patients receiving vincristine
  • No concurrent intensity-modulated radiotherapy

Who cannot join

None listed.

Trial locations and contacts

173 sites in 4 countries.

173 sites in 4 countries

United States159 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Texas Tech University Health Science Center-Amarillo

    Amarillo, Texas, 79106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Oncology Group

    Arcadia, California, 91006-3776

  • Mission Hospitals Inc

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Georgia Regents University

    Augusta, Georgia, 30912

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • 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

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • West Virginia University Charleston

    Charleston, West Virginia, 25304

  • Carolinas Medical Center

    Charlotte, North Carolina, 28203

  • Presbyterian Hospital

    Charlotte, North Carolina, 28204

  • University of Virginia

    Charlottesville, Virginia, 22908

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee, 37403

  • University of Illinois

    Chicago, Illinois, 60612

  • Childrens Memorial Hospital

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Missouri-Columbia

    Columbia, Missouri, 65212

  • 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

  • The Children's Medical Center of Dayton

    Dayton, Ohio, 45404

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

    Denver, Colorado, 80218

  • Raymond Blank Children's Hospital

    Des Moines, Iowa, 50309

  • Wayne State University

    Detroit, Michigan, 48202

  • Southern California Permanente Medical Group

    Downey, California, 90242

  • City of Hope Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Hurley Medical Center

    Flint, Michigan, 48502

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Brooke Army Medical Center

    Fort Sam Houston, Texas, 78234

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32610

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • East Carolina University

    Greenville, North Carolina, 27858

  • 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

  • University of Hawaii

    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 Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic - Jacksonville

    Jacksonville, Florida, 32207-8426

  • 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

  • Michigan State University - Breslin Cancer Center

    Lansing, Michigan, 48910

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • 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

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Loyola University Medical Center

    Maywood, Illinois, 60153

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

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Baptist Hospital of Miami

    Miami, Florida, 33176

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • 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, 06520-8032

  • 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-Main Campus

    New Orleans, Louisiana, 70118

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • New York University Langone Medical Center

    New York, New York, 10016

  • Mount Sinai Medical Center

    New York, New York, 10029

  • 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

  • Advocate Hope Children's Hospital

    Oak Lawn, Illinois, 60453

  • 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

  • M D Anderson Cancer Center- Orlando

    Orlando, Florida, 32806

  • Nemours Childrens Clinic - Orlando

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • 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

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • 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

  • Carilion Clinic Children's Hospital

    Roanoke, Virginia, 24014

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Sutter General Hospital

    Sacramento, California, 95816

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229-3900

  • Methodist Children's Hospital of South Texas

    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

  • Santa Barbara Cottage Hospital

    Santa Barbara, California, 93102

  • Memorial Health University Medical Center

    Savannah, Georgia, 31403

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

  • 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

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • 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

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

  • Montefiore Medical Center

    The Bronx, New York, 10467-2490

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

  • New York Medical College

    Valhalla, New York, 10595

  • 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

  • University of Massachusetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

Canada11 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

  • Hospital Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Switzerland2 sites

  • Swiss Pediatric Oncology Group - Bern

    Bern, 3010

  • Swiss Pediatric Oncology Group - Lausanne

    Lausanne, 1011

Other trials in Switzerland

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

Other trials in Australia

About this study

Official title: Intensive Treatment for Intermediate-Risk Relapse of Childhood B-precursor Acute Lymphoblastic Leukemia (ALL): A Randomized Trial of Vincristine Strategies

This randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell acute lymphoblastic leukemia. 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 more than one drug (combination chemotherapy) and giving the drugs in different ways and different doses may kill more cancer cells..

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the efficacy of an intensive chemotherapy regimen (based on POG-9412) for pediatric patients with intermediate-risk relapsed B-precursor acute lymphoblastic leukemia.

SECONDARY OBJECTIVES:

  1. To determine levels of minimal residual disease (MRD) present at the end of the first \& third blocks of Induction and determine if higher MRD levels at these times identify patients at higher risk of relapse who might be candidates for alternative therapies in future trials.

II. To determine whether common polymorphisms in candidate genes are associated with the frequency of vincristine adverse effects (peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion [SIADH], or constipation) and with anti-leukemic response (level of end-Induction MRD).

III. Compare, descriptively, the outcomes of patients treated with combination chemotherapy vs those treated with matched sibling-related donor hematopoietic stem cell transplantation (for those with eligible donors).

IV. To use deoxyribonucleic acid (DNA) arrays to characterize patterns of gene expression that predict treatment failure, and to compare gene expression profiles at the time of relapse with those at initial diagnosis to gain an understanding of the pathways that may be involved in disease resistance.

OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 2 treatment regimens (randomization closed as of 09/2010).

INDUCTION THERAPY 1 (WEEKS 1-5):

Regimen A: Patients receive low-dose vincristine intravenously (IV) on days 1, 8, 15, and 22; prednisone orally (PO) 3 times daily (TID) on days 1-28; doxorubicin hydrochloride IV over 15 minutes on day 1; pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22; cytarabine intrathecally (IT) on day 1; and methotrexate IT* on days 15 and 29.

Regimen B: (closed to accrual as of 09/2010)***: Patients receive high-dose vincristine IV on days 1, 8, 15, and 22 and prednisone, doxorubicin hydrochloride, pegaspargase, cytarabine, and methotrexate* as in Regimen A.

NOTE: *Central nervous system (CNS)-positive patients do not receive methotrexate IT. In both arms, CNS-positive patients receive intrathecal triple therapy (ITT) comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 8, 15, 22, and 29. CNS-positive patients not achieving remission after induction therapy 1 receive one additional dose of ITT on day 36. Patients in both arms then proceed to induction therapy 2**.

NOTE: **Patients who are CNS-positive at relapse receive induction therapy 3 BEFORE induction therapy 2.

NOTE: ***Patients already enrolled on Regimen B are crossover to Regimen A.

INDUCTION THERAPY 2 (WEEKS 6-10 or 7-11): Once blood counts recover, all patients receive etoposide phosphate IV over = 1 hour and cyclophosphamide IV over 1 hour on days 1-5; high-dose methotrexate IV continuously over 24 hours on day 22; leucovorin calcium IV or PO beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; and methotrexate IT* on days 1 and 22. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 6 and continuing until blood counts recover.

NOTE: *CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on days 1 and 22. Patients with testicular-relapse with persistent testicular disease at the end of induction therapy 1 undergo testicular radiotherapy once daily (QD), 5 days a week, for 12 days during induction therapy 2**.

NOTE: **Radiotherapy should be completed before beginning high-dose methotrexate (week 9) chemotherapy.

All patients then proceed to induction therapy 3.

INDUCTION THERAPY 3 (WEEKS 11-15 or 12-16): All patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9, and asparaginase IM on days 2 and 9. Patients also receive G-CSF IV or SC beginning on day 10 and continuing until blood counts recover. Patients with a suitable HLA-matched related donor are removed from study and proceed to stem cell transplantation. Patients without a suitable HLA-matched related donor proceed to intensification therapy 1 (as per their randomized regimen in induction therapy 1).

INTENSIFICATION THERAPY 1 (WEEKS 16-27 or 17-28):

Regimen A: Patients receive low-dose vincristine IV and high-dose methotrexate IV continuously over 24 hours on day 1; leucovorin calcium IV or orally beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; oral mercaptopurine once daily on days 2-6; etoposide phosphate IV over ≥ 1 hour and cyclophosphamide IV over 1 hour on day 8; and methotrexate IT* on day 15. Treatment repeats every 21 days for 4 courses (with the exception of IT methotrexate which repeats for only 3 courses).

Regimen B: Patients receive high-dose vincristine IV on day 1 and high-dose methotrexate, leucovorin calcium, mercaptopurine, etoposide phosphate, cyclophosphamide, and methotrexate IT* as in Regimen A. (closed to accrual as of 09/2010)

NOTE: *CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on day 15. ITT repeats every 3 weeks for 3 courses.

NOTE: ** Patients already enrolled on Regimen B are crossover to Regimen A.

Patients in both regimens then proceed to reinduction therapy (as per their randomized regimen in induction therapy 1).

REINDUCTION THERAPY (WEEKS 28-32 or 29-33):

Regimen A: Patients receive low-dose vincristine IV and doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15, oral dexamethasone twice daily on days 1-7 and 15-21, pegaspargase IM on days 2 and 15, and methotrexate IT* on days 1 and 28.

Regimen B: Patients receive high-dose vincristine IV on days 1, 8, and 15 and doxorubicin hydrochloride, dexamethasone, pegaspargase, and methotrexate IT* as in Regimen A. (closed to accrual as of 09/2010)

NOTE: *CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on days 1 and 28.

NOTE: ** Patients already enrolled on Regimen B are crossover to Regimen A. Patients in both regimens then proceed to intensification therapy 2 (as per their randomized regimen in induction therapy 1).

INTENSIFICATION THERAPY 2 (WEEKS 33-56 or 34-57):

Regimen A: Once blood counts recover, patients receive high-dose cytarabine IV over 3 hours on days 1 and 2; pegaspargase IM on day 2; low-dose vincristine IV on days 22 and 29; high-dose methotrexate IV on day 22; leucovorin calcium IV or orally beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; oral mercaptopurine once daily on days 23-27; etoposide phosphate IV over ≥ 1 hour and cyclophosphamide IV over 1 hour on day 29; and methotrexate IT* on day 36. Patients also receive G-CSF IV or SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 42 days for 4 courses (with the exception of IT methotrexate which only repeats for 3 courses).

Regimen B: Patients receive high-dose cytarabine, high-dose methotrexate, leucovorin calcium, pegaspargase, mercaptopurine, etoposide phosphate, cyclophosphamide, methotrexate IT*, and G-CSF as in Regimen A. Patients also receive high-dose vincristine IV on days 22 and 29.

NOTE: *CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on day 36. Treatment repeats every 6 weeks for 3 courses.

Patients in both regimens then proceed to maintenance therapy (as per their randomized regimen in induction therapy 1).

MAINTENANCE THERAPY (week 57-106 or 58-107):

Regimen A: Patients receive methotrexate IT on day 1* and then PO on days 8, 15, 22, 29, and 36; mercaptopurine PO QD on days 1-42; dexamethasone PO twice daily (BID) on days 1-5; and low-dose vincristine IV and cyclophosphamide IV over 1 hour on days 43, 50, 57, and 64. Treatment repeats every 70 days for 5 courses.

Regimen B: Patients receive methotrexate*, mercaptopurine, dexamethasone, and cyclophosphamide as in Regimen A. Patients also receive high-dose vincristine IV on days 43, 50, 57, and 64.

NOTE: *CNS-positive patients receive methotrexate IT on day 1, instead of oral methotrexate.

Beginning in week 1 of the first maintenance therapy course, patients with CNS relapse undergo cranial radiotherapy QD, 5 days a week, for 10 days. Patients with CNS relapse do not receive any IT therapy during maintenance therapy.

After completion of study therapy, patients are followed periodically for 5 years.

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.

  • vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given PO

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • pegaspargaseDrug

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

    Given IM

  • cytarabineDrug

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

    Given IT or IV

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IT or IV

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given PO

  • etoposideDrug

    Also called EPEG, VP-16, VP-16-213

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV or PO

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given IV or SC

  • asparaginaseDrug

    Also called ASNase, Colaspase, Crasnitin, Elspar

    Given IM

  • mercaptopurineDrug

    Also called 6-mercaptopurine, 6-MP, Leukerin, MP

    Given PO

Study groups in NCT00381680
Study groupRoleWhat they receive
Regimen A: Standard vincristine dosingActive comparatorSee detailed description.
Receives: Drug: vincristine sulfate; Drug: prednisone; Drug: doxorubicin hydrochloride; Drug: pegaspargase; Drug: cytarabine; Drug: methotrexate; Drug: dexamethasone; Drug: etoposide; Drug: cyclophosphamide; Drug: leucovorin calcium; Biological: filgrastim; Drug: asparaginase; Drug: mercaptopurine
Arm B: Randomized High Dose Vincristine regimenExperimentalSee detailed description. Closed to accrual as of 09/2010).
Receives: Drug: vincristine sulfate; Drug: prednisone; Drug: doxorubicin hydrochloride; Drug: pegaspargase; Drug: cytarabine; Drug: methotrexate; Drug: dexamethasone; Drug: etoposide; Drug: cyclophosphamide; Drug: leucovorin calcium; Biological: filgrastim; Drug: asparaginase; Drug: mercaptopurine

What is being measured

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

  1. Event Free Survival. EFS

    Percentage of patients who were event free at 3 years among those on Standard VCR dosing who did not undergo Hematopoietic Stem Cell Transplant (SCT).

    Measured: 3 years after enrollment

Secondary outcomes (6)

  1. Frequency and Severity of Adverse Effects

    Percentage of patients who developed at least 1 episode of grade 2 to 4 neuropathy.

    Measured: Up to 107 weeks

  2. Gene Expression Profile

    Percent of unfavorable gene expression profile of early versus late marrow relapse.

    Measured: Up to 36 months

  3. Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1

    Percentage of patients who had minimal residual disease (MRD) < 0.01% among those with isolated BM or combined BM relapse >= 36 months and had successful MRD determinations at End Block 1

    Measured: End of Block 1 (35 days) of Induction therapy

  4. Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3

    Percentage of patients who had minimal residual disease (MRD) < 0.01% among those with isolated BM or combined BM relapse >= 36 months and had successful MRD determinations at End Block 3.

    Measured: End of Block 3 (105 days) of Induction therapy

  5. Event Free Survival (EFS)

    Percentage of patients who were event free at 3 years among those with isolated BM or combined BM relapse >= 36 months.

    Measured: 3 years

  6. Adjusted Event Free Survival

    Adjusted percentage of patients who were event free at 3 years. For patients who received matched donor SCT, EFS was adjusted to start from the actual SCT date. For patients who did not undergo SCT, EFS was adjusted to start from median time to SCT based on patients who received matched related SCT (where patients who had events prior to SCT date were excluded from the calculation of median time to SCT).

    Measured: 3 years

Timeline

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

  1. First posted28 Sep 2006 (estimated)
  2. Study startMar 2007
  3. Primary completionMar 2016

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
275 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00381680
Sponsor's protocol ID
AALL0433
Other IDs
NCI-2009-00306, COG-AALL0433, CDR0000495359, U10CA098543
Status last verified
Mar 2024
First submitted
26 Sep 2006
Last updated
26 Mar 2024
Data monitoring committee
Yes
Individual data sharing
Yes: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

  • Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2021 Jan 1;106(1):46-55. doi: 10.3324/haematol.2019.237230.

    PubMed 32001530

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing vincristine sulfate, prednisone and doxorubicin hydrochloride in people with B-cell Childhood Acute Lymphoblastic Leukemia and L1 Childhood Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 173 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 25 inclusion and 0 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 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 173 sites in United States, Canada, Switzerland, Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 12 May 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?

Event Free Survival. EFS (time frame: 3 years after enrollment). 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 NCT00381680, which also lists 1 linked publication.

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 26 Mar 2024.

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