Combination Chemotherapy and Radiation Therapy in Treating Patients With Acute Lymphoblastic Leukemia That Has Relapsed in the CNS or Testes

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

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.

PURPOSE: This clinical trial is studying how well giving chemotherapy together with radiation therapy works in treating patients with acute lymphoblastic leukemia that has relapsed in the CNS and/or testes.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Biological: filgrastim; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: etoposide; Drug: leucovorin calcium; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Radiation: radiation therapy

Detailed Description

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 sequelae 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 cyclophosphamide 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 cyclophosphamide 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 cyclophosphamide 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.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitalier Universitaire de Quebec
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's & Women's Hospital of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Janeway Children's Health and Rehabilitation Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Cancer Centre of Southeastern Ontario at Kingston General Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hôpital Sainte Justine
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• New Zealand
  • Auckland, New Zealand, 1
    • Starship Children's Health
  • Christchurch, New Zealand, 8140
    • Christchurch Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • Swiss Pediatric Oncology Group Bern
  • Geneva, Switzerland, 1205
    • Swiss Pediatric Oncology Group Geneva
  • Lausanne, Switzerland, 1011
    • Swiss Pediatric Oncology Group Lausanne
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Comprehensive Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Downey, California, United States, 90027
      • Southern California Permanente Medical Group
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Long Beach, California, United States, 90801
      • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • Madera, California, United States, 93638-8762
      • Children's Hospital Central California
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 95798
      • Lucile Packard Children's Hospital at Stanford University Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Center - Oakland
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Center for Cancer and Blood Disorders
    • Denver, Colorado, United States, 80218
      • Presbyterian - St. Luke's Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center Cancer Center
    • Fort Myers, Florida, United States, 33901
      • Lee Cancer Care of Lee Memorial Health System
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center - Miami
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
    • Orlando, Florida, United States, 32803-1273
      • Florida Hospital Cancer Institute at Florida Hospital Orlando
    • Orlando, Florida, United States, 32806
      • Nemours Children's Clinic - Orlando
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center at Orlando
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Cancer Center at Sacred Heart Hospital
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33607
      • St. Joseph's Cancer Institute at St. Joseph's Hospital
    • West Palm Beach, Florida, United States, 33407
      • Kaplan Cancer Center at St. Mary's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Idaho
    • Boise, Idaho, United States, 83712-6297
      • Mountain States Tumor Institute at St. Luke's Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612-7243
      • University of Illinois Cancer Center
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Oak Lawn, Illinois, United States, 60453
      • Keyser Family Cancer Center at Advocate Hope Children's Hospital
    • Park Ridge, Illinois, United States, 60068-1174
      • Advocate Lutheran General Cancer Care Center
    • Springfield, Illinois, United States, 62794-9677
      • Simmons Cooper Cancer Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Indianapolis Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Blank Children's Hospital
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Louisville, Kentucky, United States, 40232
      • Kosair Children's Hospital
  • Maine
    • Bangor, Maine, United States, 04401
      • CancerCare of Maine at Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children at Tufts - New England Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0286
      • C.S. Mott Children's Hospital at University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503-2560
      • Butterworth Hospital at Spectrum Health
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Kalamazoo, Michigan, United States, 49007-5381
      • CCOP - Kalamazoo
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Cancer Clinic
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89109-2306
      • CCOP - Nevada Cancer Research Foundation
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Cancer Center
    • Morristown, New Jersey, United States, 07962
      • Overlook Hospital
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Hospital and Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Cancer Center at Albert Einstein College of Medicine
    • Brooklyn, New York, United States, 11201-5493
      • Brooklyn Hospital Center
    • Brooklyn, New York, United States, 11219
      • Maimonides Cancer Center at Maimonides Medical Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hospital
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Stony Brook, New York, United States, 11794-9446
      • Stony Brook University Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Akron Children's Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5000
      • Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43205-2696
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404-1815
      • Dayton Children's - Dayton
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Youngstown, Ohio, United States, 44501
      • Tod Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Knight Cancer Institute at Oregon Health and Science University
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center and Children's Hospital
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Cancer Institute at Geisinger Health
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Children's Hospital
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
    • Philadelphia, Pennsylvania, United States, 19104-9786
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh of UPMC
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Comprehensive Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • T.C. Thompson Children's Hospital
    • Knoxville, Tennessee, United States, 37901
      • East Tennessee Children's Hospital
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine - Amarillo
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Houston, Texas, United States, 77030-2399
      • Baylor University Medical Center - Houston
    • San Antonio, Texas, United States, 78229-3993
      • Methodist Children's Hospital of South Texas
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84113-1100
      • Primary Children's Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Falls Church, Virginia, United States, 22042-3300
      • INOVA Fairfax Hospital
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center for Children at Roanoke Community Hospital
  • Washington
    • Spokane, Washington, United States, 99220-2555
      • Providence Cancer Center at Sacred Heart Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25302
      • West Virginia University Health Sciences Center - Charleston
    • Morgantown, West Virginia, United States, 26506
      • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Center for Cancer and Blood
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 29 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CNS Patients-Treatment (combination chemotherapy); All patients receive common induction (vincristine sulfate, dexamethasone, daunorubicin hydrochloride & intrathecal triple therapy (ITT: MTX, therapeutic hydrocortisone and cytarabine)), consolidation (cytarabine, pegaspargase, filgrastim, re-induction (vincristine, dexamethasone, daunorubicin), and intensification chemotherapy (MTX, leucovorin calcium, mercaptopurine, etoposide, cyclophosphamide & ITT.	Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; given IV; Other Names: VCR; Oncovin; LCR; NSC #67574; Biological: filgrastim; given subcutaneously (SC); Other Names: G-CSF; Granulocyte Colony-Stimulating Factor; r-metHuG-CSF; Neupogen; NSC 614629; Drug: cyclophosphamide; IV over 15-30 minutes; Other Names: CYTOXAN; NSC #26271; Drug: cytarabine; IV over 3 hours twice daily; Other Names: Ara-C; Cytosar; Cytosine arabinoside; NSC #6387; Drug: daunorubicin hydrochloride; IV over 15 minutes; Other Names: Cerubidine; NSC #82151; Daunomycin; rubidomycin; Drug: dexamethasone; oral twice daily; Other Names: Decadron; Dexameth; Dexone; Hexadrol; NSC #34521; Drug: etoposide; IV over 1 hour; Other Names: VP-16; Etopophos; VePesid; NSC #141540; Drug: leucovorin calcium; rescue IV over 24 hours; Other Names: LCV; Wellcovorin; citrovorum factor; folinic acid; NSC 03590; Drug: mercaptopurine; oral; Other Names: 6-MP; Purinethol; NSC #000755; 6-mercaptopurine; Drug: methotrexate; intramuscularly (IM); Other Names: amethopterin; MTX; NSC #000740; Trexall; Drug: pegaspargase; intramuscularly (IM); Other Names: Oncaspar; PEGLA; PEG-L-asparaginase; PEG-asparaginase; polyethylene glycol-L-asparaginase; NSC 624239; Radiation: radiation therapy; Patients with isolated testicular relapse will start Induction with a single dose of high-dose methotrexate (HDMTX) and will not receive either testicular or cranial radiation. Patients with isolated CNS relapse will NOT receive the initial dose of HDMTX prior to Induction, but will receive 1200 cGy of cranial radiation after completing the initial 12 months of intensive systemic chemotherapy.
Experimental: Testicular Relapse Patients (Combination chemotherapy); All patients receive common induction (vincristine sulfate, dexamethasone, daunorubicin hydrochloride & intrathecal triple therapy (ITT: MTX, therapeutic hydrocortisone and cytarabine)), consolidation (cytarabine, pegaspargase, filgrastim, testicular radiation therapy, re-induction (vincristine, dexamethasone, daunorubicin), and intensification chemotherapy (MTX, leucovorin calcium, mercaptopurine, etoposide, cyclophosphamide & ITT.	Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; given IV; Other Names: VCR; Oncovin; LCR; NSC #67574; Biological: filgrastim; given subcutaneously (SC); Other Names: G-CSF; Granulocyte Colony-Stimulating Factor; r-metHuG-CSF; Neupogen; NSC 614629; Drug: cyclophosphamide; IV over 15-30 minutes; Other Names: CYTOXAN; NSC #26271; Drug: cytarabine; IV over 3 hours twice daily; Other Names: Ara-C; Cytosar; Cytosine arabinoside; NSC #6387; Drug: daunorubicin hydrochloride; IV over 15 minutes; Other Names: Cerubidine; NSC #82151; Daunomycin; rubidomycin; Drug: dexamethasone; oral twice daily; Other Names: Decadron; Dexameth; Dexone; Hexadrol; NSC #34521; Drug: etoposide; IV over 1 hour; Other Names: VP-16; Etopophos; VePesid; NSC #141540; Drug: leucovorin calcium; rescue IV over 24 hours; Other Names: LCV; Wellcovorin; citrovorum factor; folinic acid; NSC 03590; Drug: mercaptopurine; oral; Other Names: 6-MP; Purinethol; NSC #000755; 6-mercaptopurine; Drug: methotrexate; intramuscularly (IM); Other Names: amethopterin; MTX; NSC #000740; Trexall; Drug: pegaspargase; intramuscularly (IM); Other Names: Oncaspar; PEGLA; PEG-L-asparaginase; PEG-asparaginase; polyethylene glycol-L-asparaginase; NSC 624239; Radiation: radiation therapy; Patients with isolated testicular relapse will start Induction with a single dose of high-dose methotrexate (HDMTX) and will not receive either testicular or cranial radiation. Patients with isolated CNS relapse will NOT receive the initial dose of HDMTX prior to Induction, but will receive 1200 cGy of cranial radiation after completing the initial 12 months of intensive systemic chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival	Monitoring of efficacy results will be performed in comparison with historical results.	3 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Julio C. Barredo, MD, University of Miami Miller School of Medicine-Sylvester Cancer Center; Study Chair: Caroline A. Hastings, MD, UCSF Benioff Children's Hospital Oakland

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimate): November 9, 2004

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: B-cell childhood acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; TdT positive childhood acute lymphoblastic leukemia; T-cell childhood acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Micronutrients; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Vitamins; Reproductive Control Agents; Antidotes; Vitamin B Complex; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Cyclophosphamide; Etoposide; Leucovorin; Levoleucovorin; Lenograstim; Cytarabine; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Pegaspargase
• Other Study ID Numbers: AALL02P2; COG-AALL02P2 (Other Identifier: Children's Oncology Group); NCI-2011-01623 (Other Identifier: NCI Trial Identifier)