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High Risk B-Precursor Acute Lymphoblastic Leukemia


Phase 3
1 Year
30 Years
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

High Risk B-Precursor Acute Lymphoblastic Leukemia


OBJECTIVES:

- Compare the outcome of patients with high-risk acute lymphoblastic leukemia treated
with 2 different chemotherapy regimens.

- Compare the relative safety and efficacy of dexamethasone vs prednisone during
induction therapy in patients treated with these regimens.

- Compare the relative safety and efficacy of high-dose methotrexate with leucovorin
rescue vs escalating methotrexate without leucovorin rescue during interim maintenance
I in patients treated with these regimens.

- Correlate minimal residual disease (MRD) at day 29 with event-free survival and overall
survival of patients treated with these regimens.

- Correlate early marrow response status with day-29 MRD in patients treated with these
regimens.

- Identify additional high-risk patients for treatment with the fully augmented
Berlin-Frankfurt-Munster regimen by using day-29 MRD.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to early
response (slow early response [SER] vs rapid early response [RER]).

- Induction therapy: Patients are randomized to 1 of 4 treatment arms.

- Arm I: Patients receive intrathecal (IT) cytarabine on day 1; vincristine IV and
daunorubicin IV on days 1, 8, 15, and 22; oral or IV dexamethasone twice daily on
days 1-14; IT methotrexate (MTX) on days 8 and 29*; and pegaspargase
intramuscularly (IM) once on day 4, 5, or 6.

NOTE: *Patients with CNS3 disease (WBC > 5/mL in cerebrospinal fluid and positive for blasts
on cytospin) also receive IT MTX on days 15 and 22.

- Arm II: Patients receive induction therapy as in arm I.

- Arm III: Patients receive cytarabine, vincristine, daunorubicin, and pegaspargase as in
arm I. Patients also receive oral or IV prednisone twice daily on days 1-28 and IT MTX
on days 8 and 29.

- Arm IV: Patients receive induction therapy as in arm III. Patients in all arms are
evaluated at day 29 of induction therapy. Patients with M3 disease are removed from
study. Patients with M1 disease and less than 1% minimal residual disease (MRD) proceed
to consolidation therapy beginning on day 36. Patients with M2 disease OR with MI
disease and at least 1% MRD receive extended induction therapy for 2 additional weeks.
Patients with SER disease and MLL rearrangements are removed from the study but may be
eligible for treatment on protocol COG-AALL0031.

- Extended induction therapy: Patients continue to receive therapy on the arm to
which they were originally randomized.

- Arms I and II: Patients receive oral or IV dexamethasone twice daily on days 1-14;
vincristine IV on days 1 and 8; daunorubicin IV on day 1; and pegaspargase IM on day 4,
5, or 6 and are then reevaluated.

- Arms III and IV: Patients receive oral or IV prednisone twice daily on days 1-14, and
vincristine, daunorubicin, and pegaspargase as in arms I and II and are then
reevaluated.

Patients on all arms who have M1 disease and less than 1% MRD after extended induction
proceed to consolidation therapy and continue as SER patients. All other patients are
removed from study.

- Consolidation therapy: All patients receive cyclophosphamide IV over 30 minutes on days
1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39;
oral mercaptopurine (MP) on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and
50; pegaspargase IM on days 15 and 43; and IT MTX* on days 1, 8, 15, and 22. Patients
with testicular disease also receive radiotherapy to the testes.

NOTE: *Patients with CNS3 disease receive MTX on days 1 and 8 only.

- Interim maintenance therapy I: Patients continue to receive treatment on the arm to
which they were originally randomized.

- Arm I (escalating-dose MTX): Patients receive vincristine IV and escalating-dose
MTX IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and IT MTX
on days 1 and 21.

- Arm II (high-dose MTX): Patients receive vincristine IV and high-dose methotrexate
IV over 24 hours on days 1, 15, 29, and 43; oral MP on days 1-56; and IT MTX on
days 1 and 29. Patients also receive leucovorin calcium IV every 6 hours for at
least 3 doses, beginning 42 hours after start of each MTX infusion.

- Arm III (escalating-dose MTX): Patients receive interim maintenance I therapy as
in arm I.

- Arm IV (high-dose MTX): Patients receive interim maintenance I therapy as in arm
II.

- Delayed intensification therapy I: All patients receive vincristine IV on days 1, 8,
15, 43, and 50; oral or IV dexamethasone twice daily on days 1 to 21 for patients age 1
to 12 OR on days 1-7 and 15-21 for patients age 13 and over; doxorubicin IV on days 1,
8, and 15; pegaspargase IM on day 4, 5, or 6 AND day 43; cyclophosphamide IV over 30
minutes on day 29; cytarabine IV or SC on days 30-33 and 37-40; oral thioguanine on
days 29-42; and IT MTX on days 1, 29, and 36.

After delayed intensification I, SER patients proceed to interim maintenance II and delayed
intensification II. RER patients proceed directly to maintenance.

- Interim maintenance therapy II: All patients receive vincristine IV and MTX IV on days
1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and IT MTX on days 1 and 21.
Patients then proceed to delayed intensification II.

- Delayed intensification therapy II: All patients receive therapy as in delayed
intensification I, arm I. CNS3 patients also receive radiotherapy for 3-10 days,
beginning on day 29. All other SER patients, patients with MLL rearrangements, and some
patients pretreated with steroids (> 48 hours within the week prior to diagnosis)
receive prophylactic cranial radiotherapy (CRT) for 8 days, beginning on day 29.
Patients then proceed to maintenance therapy.

- Maintenance therapy: All patients receive vincristine IV on days 1, 29, and 57; oral
dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral MP on days 1-84; IT MTX
on day 1*; and oral MTX on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

NOTE: *RER (who did not undergo CRT) patients also receive IT MTX on day 29 for maintenance
courses 1-4.

In all arms, maintenance therapy repeats every 12 weeks until total duration of therapy is 2
years from the start of interim maintenance I for female patients and 3 years from the start
of interim maintenance I for male patients. Patients with testicular disease may receive
testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1
year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 2,964 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed B-precursor acute lymphoblastic leukemia

- WBC > 50,000/mm^3 for patients age 1 to 9

- Any WBC for patients age 10 to 30 OR patients who have received prior steroid
therapy OR patients with testicular disease

- Must be eligible for and enrolled on classification study COG-AALL03B1

PATIENT CHARACTERISTICS:

Age

- 1 to under 31

Performance status

- Not specified

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

Hepatic

- Not specified

Renal

- Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No more than 72 hours since prior intrathecal cytarabine

- No other prior cytotoxic chemotherapy

Endocrine therapy

- Prior steroids allowed

Radiotherapy

- Not specified

Surgery

- Not specified

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparison of the increase in cure rate of high risk ALL without causing more serious side effects between interventions

Outcome Description:

Compared using a two-sided log rank test.

Outcome Time Frame:

During the first month of treatment

Safety Issue:

No

Principal Investigator

Eric C. Larsen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Maine Children's Cancer Program at Barbara Bush Children's Hospital

Authority:

United States: Federal Government

Study ID:

AALL0232

NCT ID:

NCT00075725

Start Date:

December 2003

Completion Date:

Related Keywords:

  • Leukemia
  • untreated childhood acute lymphoblastic leukemia
  • B-cell childhood acute lymphoblastic leukemia
  • untreated adult acute lymphoblastic leukemia
  • B-cell adult acute lymphoblastic leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
Walter Reed Army Medical CenterWashington, District of Columbia  20307-5000
University of Chicago Cancer Research CenterChicago, Illinois  60637
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
Baystate Regional Cancer Program at D'Amour Center for Cancer CareSpringfield, Massachusetts  01199
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
CCOP - MeritCare HospitalFargo, North Dakota  58122
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Avera Cancer InstituteSioux Falls, South Dakota  57105
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
University of Texas Medical BranchGalveston, Texas  77555-1329
Deaconess Medical CenterSpokane, Washington  99210-0248
Rush University Medical CenterChicago, Illinois  60612-3824
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
UMASS Memorial Cancer Center - University CampusWorcester, Massachusetts  01605-2982
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Schneider Children's HospitalNew Hyde Park, New York  11042
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
Driscoll Children's HospitalCorpus Christi, Texas  78466
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Brookdale University Hospital and Medical CenterBrooklyn, New York  11212
Brooklyn Hospital CenterBrooklyn, New York  11201
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Covenant Children's HospitalLubbock, Texas  79410
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Midwest Children's Cancer Center at Children's Hospital of WisconsinMilwaukee, Wisconsin  53226
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Overlook HospitalSummit, New Jersey  07902-0220
Winthrop University HospitalMineola, New York  11501
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
Santa Barbara Cottage Children's HospitalSanta Barbara, California  93105
Yale Cancer CenterNew Haven, Connecticut  06520-8028
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Baptist-South Miami Regional Cancer ProgramMiami, Florida  33176
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Blank Children's HospitalDes Moines, Iowa  50309
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Floating Hospital for Children at Tufts - New England Medical CenterBoston, Massachusetts  02111
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Mount Sinai Medical CenterNew York, New York  10029
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Naval Medical Center - PortsmouthPortsmouth, Virginia  23708-2197
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
William Beaumont Hospital - Royal Oak CampusRoyal Oak, Michigan  48073
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
University of South Alabama Mitchell Cancer InstituteMobile, Alabama  36604
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781
Childrens Hospital Los AngelesLos Angeles, California  90027
Children's Hospital and Research Center OaklandOakland, California  94609
Lucile Packard Children's Hospital at Stanford University Medical CenterPalo Alto, California  95798
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Kaiser Permanente Medical Center - Santa Clara Kiely CampusSanta Clara, California  95051-5386
Children's Hospital Center for Cancer and Blood DisordersAurora, Colorado  80045
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
MBCCOP - Medical College of Georgia Cancer CenterAugusta, Georgia  30912-3730
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Keyser Family Cancer Center at Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Advocate Lutheran General Cancer Care CenterPark Ridge, Illinois  60068-1174
Simmons Cooper Cancer InstituteSpringfield, Illinois  62794-9677
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
Maine Children's Cancer Program at Barbara Bush Children's HospitalScarborough, Maine  04074-9308
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Masonic Cancer Center at University of MinnesotaMinneapolis, Minnesota  55455
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
Children's Hospitals and Clinics of Minnesota - St. PaulSt. Paul, Minnesota  55102-2392
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Children's HospitalOmaha, Nebraska  68114-4113
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
St. Barnabas Medical Center Cancer CenterLivingston, New Jersey  07039
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Albany Medical Center HospitalAlbany, New York  12208-3419
Maimonides Cancer Center at Maimonides Medical CenterBrooklyn, New York  11219
Akron Children's HospitalAkron, Ohio  44308-1062
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Tod Children's HospitalYoungstown, Ohio  44501
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
Legacy Emanuel Hospital and Health Center and Children's HospitalPortland, Oregon  97227
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Penn State Children's HospitalHershey, Pennsylvania  17033-0850
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central TexasAustin, Texas  78723
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Carilion Medical Center for Children at Roanoke Community HospitalRoanoke, Virginia  24014
Madigan Army Medical Center - TacomaTacoma, Washington  98431
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
University of Virginia Cancer CenterCharlottesville, Virginia  22908
Massachusetts General HospitalBoston, Massachusetts  02114-2617
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Leo W. Jenkins Cancer Center at ECU Medical SchoolGreenville, North Carolina  27834
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Greenville Hospital Cancer CenterGreenville, South Carolina  29605
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Banner Desert Medical CenterMesa, Arizona  85202
Connecticut Children's Medical CenterHartford, Connecticut  06106