Combination Chemotherapy in Treating Children With Very High Risk Acute Lymphocytic Leukemia

July 24, 2014 updated by: Children's Oncology Group

ALinC 17: Continuous Intensification for Very High Risk Acute Lymphocytic Leukemia (A.L.L.): A Pediatric Oncology Group Pilot Study

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and combining drugs in different ways may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy in treating children who have very high risk acute lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine the feasibility of administering a new combination of agents during postinduction consolidation therapy in children with very high risk acute lymphocytic leukemia (VHR-ALL). II. Assess the tolerance of patients in remission of VHR-ALL for postconsolidation therapy with continuous intensification.

OUTLINE: Patients receive induction therapy on weeks 1-4. This consists of oral prednisone three times a day on days 1-28; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, and 22; and asparaginase IM on days 2, 5, 8, 12, 15, and 19. Patients also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 and 3 disease also receive methotrexate IT on days 15 and 22. Patients who achieve M2 bone marrow on day 29 receive oral prednisone three times a day on days 29-42; vincristine IV and daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36, and 39. If bone marrow is M3 on day 29 or M2 or M3 on day 43, then patient is off study. Patients proceed to consolidation therapy on weeks 5-25. This consists of high dose methotrexate IV over 24 hours on weeks 6, 8, 16, and 18, followed by leucovorin calcium IV or orally every 6 hours for 5 doses; oral mercaptopurine on weeks 6-9 and 16-19; cytarabine IV over 6 hours followed by idarubicin IV over 15 minutes for 4 days; and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 5 and continuing for about 10-14 days on weeks 10 and 20. Patients receive etoposide IV over 1 hour followed by cyclophosphamide IV over 10 minutes for 5 days and G-CSF SQ beginning on day 6 for 10-14 days on weeks 13 and 23. Methotrexate IT is administered on weeks 6, 8, 13, 16, 18, and 23. Patients then proceed to continuous intensification therapy during weeks 26-61. Patients receive vincristine IV, daunorubicin IV, and methotrexate IT on day 1, and oral dexamethasone twice a day on days 1-7 on weeks 26, 32, 38, 44, 50, and 56. Patients also receive high dose cytarabine IV over 1 hour, every 12 hours, for 4 doses, followed by asparaginase IM 3 hours after the last dose of cytarabine, on weeks 27, 33, 39, 45, 51, and 57. Oral mercaptopurine and methotrexate IM are administered on day 1 during weeks 29, 31, 35, 37, 41, 43, 47, 49, 53, 55, 59, and 61. Patients receive etoposide IV over 1-2 hours followed by cyclophosphamide IV during weeks 30, 36, 42, 48, 54, and 60. Patients then proceed to continuation therapy during weeks 62-126. Vincristine IV and cyclophosphamide IV are administered on weeks 62-65, 70-73, 78-81, 86-89, 94-97, 102-105, 110-113, and 118-121. Patients also receive oral dexamethasone twice a day for 7 days on weeks 62, 70, 78, 86, 94, 102, 110, and 118, and cytarabine IV on weeks 63, 65, 71, 73, 79, 81, 87, 89, 95, 97, 103, 105, 111, 113, 119, and 121. Oral mercaptopurine is administered daily during weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125 and methotrexate IM on weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125. Methotrexate IT is administered during weeks 62, 70, 78, 86, 94, 102, 110, and 118. Patients who are CNS 3 at diagnosis receive whole brain irradiation beginning at week 62 along with the first course of continuation therapy. These patients do not receive any methotrexate IT after week 62. 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, then annually thereafter.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 12 months.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • Alberta Children's Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital
      • Sainte Foy, Quebec, Canada, GIV 4G2
        • Centre Hospitalier de l'Universite Laval
  • Netherlands
      • Groningen, Netherlands, 9713 EZ
        • Academisch Ziekenhuis Groningen
  • Puerto Rico
      • Santurce, Puerto Rico, 00912
        • San Jorge Childrens Hospital
  • Switzerland
      • Geneva, Switzerland, 1211
        • Clinique de Pediatrie
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Arizona Cancer Center
    • California
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital at Stanford
      • Sacramento, California, United States, 95816
        • Sutter Cancer center
      • San Diego, California, United States, 92120
        • Kaiser Permanente-Southern California Permanente Medical Group
      • San Diego, California, United States, 92134-3202
        • Naval Medical Center - San Diego
      • Santa Clara, California, United States, 95051-5386
        • Kaiser Permanente Medical Center - Santa Clara
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Miami, Florida, United States, 33136
        • Sylvester Cancer Center, University of Miami
      • Miami, Florida, United States, 33176-2197
        • Baptist Hospital of Miami
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Comprehensive Cancer Center
      • Orlando, Florida, United States, 32803
        • Walt Disney Memorial Cancer Institute
      • West Palm Beach, Florida, United States, 33407
        • St. Mary's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
    • Hawaii
      • Honolulu, Hawaii, United States, 96859-5000
        • Tripler Army Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush-Presbyterian-St. Luke's Medical Center
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital, Chicago
      • Oak Lawn, Illinois, United States, 60453
        • Hope Children's Hospital
      • Peoria, Illinois, United States, 61602
        • Saint Jude Midwest Affiliate
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Via Christi Regional Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Portland, Maine, United States, 04101
        • Maine Children's Cancer Program
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48236
        • St. John's Hospital and Medical Center
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
      • Keesler AFB, Mississippi, United States, 39534-2576
        • Keesler Medical Center - Keesler AFB
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri-Columbia Hospital and Clinics
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Norris Cotton Cancer Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico School of Medicine
    • New York
      • Stony Brook, New York, United States, 11790-7775
        • State University of New York Health Sciences Center - Stony Brook
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73126-0307
        • Oklahoma Memorial Hospital
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center
    • Tennessee
      • Johnson City, Tennessee, United States, 37614-0622
        • James H. Quillen College of Medicine
    • Texas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Dallas, Texas, United States, 75235-9154
        • Simmons Cancer Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Galveston, Texas, United States, 77555-0209
        • University of Texas Medical Branch
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Lackland Air Force Base, Texas, United States, 78236-5300
        • San Antonio Military Pediatric Cancer and Blood Disorders Center
      • Temple, Texas, United States, 76508
        • Scott and White Clinic
    • Vermont
      • Burlington, Vermont, United States, 05401-3498
        • Vermont Cancer Center
    • Virginia
      • Falls Church, Virginia, United States, 22046
        • Inova Fairfax Hospital
      • Roanoke, Virginia, United States, 24029
        • Carilion Roanoke Community Hospital
    • Washington
      • Tacoma, Washington, United States, 98431-5000
        • Madigan Army Medical Center
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Medical School, Charleston Division
      • Morgantown, West Virginia, United States, 26506-9162
        • West Virginia University Hospitals
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54307-3508
        • St. Vincent Hospital
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Newly diagnosed B-cell precursor acute lymphocytic leukemia No L3 morphology Very poor prognosis CNS 3 (blasts and WBC greater than 5 microliters) OR Must meet all of the following criteria: No simultaneous trisomy 4 and 10 DNA index no greater than 1.16 (if FISH 4 and 10 unsatisfactory) No TEL-AML1 [t(12;21)] Meets at least 1 of the following: Has MLL (11q23) and/or BCR-ABL [t(9;22)] WBC greater than 100,000/mm3 Age over 12 (boys) or 16 (girls) OR Boys Girls WBC 8 12 greater than 80,000/mm3 9 13 greater than 60,000/mm3 10 14 greater than 40,000/mm3 11 15 greater than 20,000/mm3 Concurrent registration on stratum 6 of POG-9400 before 11/15/1999 OR Concurrent registration on stratum 4 of POG-9900 after 11/15/1999 Concurrent registration on POG-9201, POG-9705, or POG-9806 unless ineligible

PATIENT CHARACTERISTICS: Age: Children Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified

PRIOR CONCURRENT THERAPY: See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Complete Response and no CNS 3
See detailed description.
Drug: cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
  • NSC #026271
Drug: leucovorin calcium
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Radiation: radiation therapy
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #010023
Drug: asparaginase
Other Names:
  • E. coli
  • Elspar
  • NSC #109229
Drug: cytarabine
Other Names:
  • Ara-C
  • Cytosar
  • cytosine arabinoside
  • NSC #063878
Drug: daunorubicin hydrochloride
Other Names:
  • Cerubidine
  • daunomycin
  • DNR
  • NSC #82151
Drug: dexamethasone
Other Names:
  • Decadron
  • NSC #034521
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
Drug: methotrexate
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • IND #4291
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Drug: mercaptopurine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #000755
Biological: filgrastim
Other Names:
  • G-CSF
Drug: idarubicin
Other Names:
  • Idamycin
  • 4-demethoxydaunorubicin
  • NSC #256439
Experimental: Complete Response and CNS 3
See detailed description.
Drug: cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
  • NSC #026271
Drug: leucovorin calcium
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Radiation: radiation therapy
Drug: prednisone
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #010023
Drug: asparaginase
Other Names:
  • E. coli
  • Elspar
  • NSC #109229
Drug: cytarabine
Other Names:
  • Ara-C
  • Cytosar
  • cytosine arabinoside
  • NSC #063878
Drug: daunorubicin hydrochloride
Other Names:
  • Cerubidine
  • daunomycin
  • DNR
  • NSC #82151
Drug: dexamethasone
Other Names:
  • Decadron
  • NSC #034521
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
Drug: methotrexate
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • IND #4291
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Drug: mercaptopurine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #000755
Biological: filgrastim
Other Names:
  • G-CSF
Drug: idarubicin
Other Names:
  • Idamycin
  • 4-demethoxydaunorubicin
  • NSC #256439

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Assess the feasibility of delivering a new combination of agents during a 20 week post-induction consolidation phase
Time Frame: 20 weeks
20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: William P. Bowman, MD, Cook Children's Medical Center - Fort Worth

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1999

Primary Completion (Actual)

November 1, 2002

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

April 26, 2004

First Posted (Estimate)

April 27, 2004

Study Record Updates

Last Update Posted (Estimate)

July 28, 2014

Last Update Submitted That Met QC Criteria

July 24, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9806
  • POG-9806 (Other Identifier: Pediatric Oncology Group)
  • CDR0000066915 (Other Identifier: NCI)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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