Know Cancer

or
forgot password

Treatment of Late Isolated Extramedullary Relapse From Acute Lymphoblastic Leukemia (ALL) (Initial CR1≥ 18 Months)


N/A
1 Year
29 Years
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

Treatment of Late Isolated Extramedullary Relapse From Acute Lymphoblastic Leukemia (ALL) (Initial CR1≥ 18 Months)


OBJECTIVES:

Primary

- Determine the efficacy of intensified systemic chemotherapy with reduced-dose CNS
radiotherapy in patients with acute lymphoblastic leukemia and late isolated CNS
relapse.

- Determine the efficacy of intensive systemic chemotherapy without testicular
radiotherapy in patients with acute lymphoblastic leukemia and late isolated testicular
relapse.

- Determine the toxicity of these regimens in these patients.

Secondary

- Determine whether bone marrow involvement is present at the time of extramedullary
relapse in patients treated with these regimens.

- Correlate pretreatment minimal residual disease with outcomes in patients treated with
these regimens.

- Correlate the role of host gene polymorphisms with toxicity of these regimens and
incidence and outcome in these patients.

- Determine the neuropsychological sequalae associated with isolated CNS relapse and
these treatment regimens in these patients.

OUTLINE: This is a pilot, multicenter study. All patients receive common induction,
consolidation, re-induction, and intensification chemotherapy. Patients are stratified to
maintenance therapy according to site of extramedullary relapse (CNS vs testicular).

- Induction therapy (weeks 1-4): Patients receive vincristine IV on days 1, 8, 15, and
22; oral dexamethasone twice daily on days 1-28; daunorubicin* IV over 15 minutes on
days 1, 8, and 15; and intrathecal triple therapy** (ITT) comprising methotrexate,
hydrocortisone, and cytarabine on days 1, 8, 15, and 22.

NOTE: *The total dose of anthracyclines on this study is capped at 450 mg/m2. Once this dose
is reached, all subsequent doses of daunorubicin are omitted.

NOTE: **Patients with isolated testicular relapse receive ITT on day 1 only.

In addition to the above, patients with isolated testicular relapse also receive high-dose
methotrexate IV continuously over 24 hours on day -14. Patients with clinical signs of
disease at the end of induction undergo testicular biopsy.

Patients with CNS disease who do not achieve CNS remission after induction therapy receive
additional ITT as above on days 29 and 36.

- Consolidation therapy (weeks 5-10): Patients receive high-dose cytarabine IV over 3
hours twice daily on days 1-2 and 22-23 and pegaspargase intramuscularly (IM) on days 2
and 23. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on days
3 and 24 and continuing until blood counts recover.

Patients with isolated testicular relapse with positive biopsy results at the end of
induction undergo testicular radiotherapy once daily for a total of 12 fractions during
consolidation therapy.

- Intensification I (weeks 11-22): Patients receive high-dose methotrexate with
leucovorin calcium rescue IV over 24 hours on days 1, 22, 43, and 64 and oral
mercaptopurine once daily on days 2-6, 23-27, 44-48, and 65-69. Patients also receive
etoposide IV over 1 hour and cyclophosphomide IV over 15-30 minutes on days 8, 29, 50,
and 71. Patients receive ITT* on days 15, 36, 57, and 78.

NOTE: *Patients with isolated testicular relapse receive ITT on days 36 and 78 only.

- Reinduction therapy (weeks 23-26): Patients receive vincristine IV on days 1, 8, 15,
and 22; oral dexamethasone twice daily on days 1-7 and 15-21, and daunorubicin IV over
15 minutes on days 1, 8, and 15.

- Intensification II (weeks 27-50): Patients receive high-dose cytarabine IV over 3 hours
twice daily on days 1-2, 43-44, 85-86, and 127-128; pegaspargase IM on days 2, 44, 86,
and 128; ITT* on days 22, 64, 106, and 148; high-dose methotrexate IV continuously over
24 hours on days 29, 71, 113, and 155; oral mercaptopurine on days 30-34, 72-76,
114-118, and 156-160; and etoposide IV over 1 hour and cyclophosphamide IV over 15-30
minutes on days 36, 78, 120, and 162. Patients also receive G-CSF SC beginning on days
3, 45, 87, and 129 and continuing until blood counts recover.

NOTE: *Patients with isolated testicular relapse receive ITT on days 22 and 106 only.

- Chemotherapy and radiotherapy (weeks 51-54): Patients receive oral dexamethasone twice
daily on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, and pegaspargase IM
on days 1 and 15.

Patients with isolated CNS relapse also undergo cranial radiotherapy once daily, 5 days a
week, for a total of 12 fractions.

- Maintenance therapy for isolated CNS relapse: (weeks 55-104): Patients receive
dexamethasone PO orIV twice daily on days 1-5; oral mercaptopurine once daily on days
1-42; methotrexate IM on days 1, 8, 15, 22, 29, and 36; and vincristine IV and
cyclophosphomide IV over 1 hour on days 43, 50, 57, and 64. Treatment repeats every 10
weeks for 5 courses.

- Maintenance therapy for isolated testicular relapse:

- (Weeks 55-74): Patients receive ITT on day 1 and dexamethasone, mercaptopurine,
methotrexate, vincristine, and cyclophosphomide as in maintenance therapy for
isolated CNS relapse. Treatment repeats every 10 weeks for 2 courses.

- (Weeks 75-106): Patients receive vincristine IV on day 1; dexamethasone orally or
IV on days 1-5; oral mercaptopurine on days 1-28; and methotrexate IM on days 1,
8, 15, and 22. Treatment repeats every 28 days for 8 courses. Patients also
receive ITT on day 1 every 12 weeks for 3 doses.

Patients with combined testicular and CNS relapse receive high-dose methotrexate IV
continuously over 24 hours on day -14 in addition to the same chemotherapy and radiotherapy
administered during the induction, consolidation, intensification I, reinduction,
intensification II, and maintenance phases of therapy as isolated CNS relapse patients.

All patients undergo neuropsychological assessment within 3 months after completion of
induction therapy (before cranial radiotherapy) and at 2 years after completion of
treatment.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 257 patients (143 with isolated CNS relapse and 114 with
isolated testicular relapse) will be accrued for this study within 5.7 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of acute lymphoblastic leukemia (ALL)

- B-precursor lineage (T-precursor lineage closed to accrual as of 05/20/10)

- In first bone marrow remission (M1 by morphology) AND duration of first complete
remission ≥ 18 months from time of initial diagnosis

- First isolated CNS and/or testicular relapse

- Isolated CNS relapse, as defined by 1 of the following:

- WBC ≥ 5/mm^3 in cerebrospinal fluid (CSF) with blasts present on cytospin

- Any number of WBC in CSF with immunophenotypic proof of leukemic relapse,
defined by the following:

- Identifiable blasts AND 1 of the following:

- B-lineage (TdT OR CD-10-positive on 2 consecutive CSF samples
obtained 4 weeks apart)

- T-lineage (TdT AND CD-7 OR TdT positivity alone on 2 consecutive
CSF samples obtained 4 weeks apart) (Closed to accrual as of
05/20/10)

- Isolated testicular relapse, defined as biopsy proven testicular involvement

- No Down syndrome

- No T-cell ALL or T-cell non-Hodgkin lymphoma

- No known optic nerve and/or retinal involvement

PATIENT CHARACTERISTICS:

Age

- 18 months to 29 years at relapse

Performance status

- Karnofsky 30-100% (for patients > 16 years of age) OR

- Lansky 30-100% (for patients ≤ 16 years of age)

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Creatinine adjusted according to age as follows:

- No greater than 0.4 mg/dL (≤ 5 months)

- No greater than 0.5 mg/dL (6 months -11 months)

- No greater than 0.6 mg/dL (1 year-23 months)

- No greater than 0.8 mg/dL (2 years-5 years)

- No greater than 1.0 mg/dL (6 years-9 years)

- No greater than 1.2 mg/dL (10 years-12 years)

- No greater than 1.4 mg/dL (13 years and over [female])

- No greater than 1.5 mg/dL (13 years to 15 years [male])

- No greater than 1.7 mg/dL (16 years and over [male]) OR

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular

- Shortening fraction ≥ 27% by echocardiogram OR

- Ejection fraction ≥ 50% by MUGA

Other

- Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior bone marrow transplantation

Chemotherapy

- Prior total anthracycline dosage ≤ 360 mg/m^2

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- No prior systemic therapy for concurrent extramedullary relapse

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Event-free survival

Outcome Description:

Monitoring of efficacy results will be performed in comparison with historical results.

Outcome Time Frame:

3 years

Safety Issue:

No

Principal Investigator

Julio C. Barredo, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Medical University of South Carolina

Authority:

United States: Federal Government

Study ID:

AALL02P2

NCT ID:

NCT00096135

Start Date:

September 2008

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • B-cell childhood acute lymphoblastic leukemia
  • T-cell childhood acute lymphoblastic leukemia
  • TdT positive childhood 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
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
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
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
CCOP - MeritCare HospitalFargo, North Dakota  58122
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Sutter Cancer CenterSacramento, California  95816
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
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
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
Brooklyn Hospital CenterBrooklyn, New York  11201
East Tennessee Children's HospitalKnoxville, Tennessee  37901
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
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
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Medical University of Ohio Cancer CenterToledo, Ohio  43614
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
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
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
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
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
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Children's Hospital Center for Cancer and Blood DisordersAurora, Colorado  80045
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
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
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
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
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
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
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
Maimonides Cancer Center at Maimonides Medical CenterBrooklyn, New York  11219
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
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
Carilion Medical Center for Children at Roanoke Community HospitalRoanoke, Virginia  24014
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Greenville Hospital Cancer CenterGreenville, South Carolina  29605
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403
Connecticut Children's Medical CenterHartford, Connecticut  06106