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Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00005603
First received: May 2, 2000
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for acute lymphoblastic leukemia.

PURPOSE: Phase III trial to determine the effectiveness of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: thioguanine
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: ALinC 17: Protocol for Patients With Newly Diagnosed High Risk Acute Lymphoblastic Leukemia (ALL) - Evaluation of the Augmented BFM Regimen: A Phase III Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy [ Designated as safety issue: Yes ]
    To determine for patients at high risk for treatment failure if the augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy, on the basis of historical controls.


Enrollment: 276
Study Start Date: March 2000
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

OBJECTIVES:

  • Determine whether augmented BFM therapy is superior to ALinc 14/15 therapy in patients with newly diagnosed high-risk acute lymphoblastic leukemia.
  • Determine whether minimal residual disease after induction therapy is predictive of an inferior prognosis in this patient population.
  • Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.

OUTLINE: Patients are stratified by CNS or testicular disease (yes vs no).

  • Induction therapy (weeks 1-5): Patients receive oral prednisone 3 times daily on days 1-29; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, 22; and asparaginase intramuscularly (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 or 3 disease also receive methotrexate IT on days 15 and 22.

Patients with M1 bone marrow proceed to consolidation therapy. Patients achieving M2 bone marrow on day 29 receive oral prednisone 3 times daily 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 on day 43, then patient is off study.

  • Consolidation therapy (weeks 6-14): Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine subcutaneously (SC) or IV on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine daily on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; asparaginase IM on days 15, 17, 19, 22, 24, 26, 43, 45, 47, 50, 52, and 54; and methotrexate IT on days 1, 15, 29, and 43.

Patients then proceed to interim maintenance and delayed intensification on weeks 15-46. Courses repeat every 16 weeks.

  • Maintenance I and II (weeks 15-22 and 31-38): Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; asparaginase IM on days 2, 12, 22, 32, and 42; and methotrexate IT on days 1 and 31.
  • Delayed Intensification (weeks 23-36 and 39-42): Patients receive vincristine IV on days 57, 64, and 71; methotrexate IT on day 57; oral dexamethasone 2-3 times daily on days 57-63 and 71-77; doxorubicin IV over 15 minutes 3 times weekly on days 57, 64, and 71; and asparaginase IM on days 60, 62, 64, 67, 69, and 71.
  • Delayed Intensification-Reconsolidation (weeks 27-30 and 43-46): Patients receive oral thioguanine on days 85-98; methotrexate IT on day 85; cyclophosphamide IV over 30 minutes on day 85; cytarabine IV or SC on days 86-89 and 93-96; asparaginase IM on days 99, 101, 103, 106, 108, and 110; and vincristine IV on days 99 and 106.
  • Continuation therapy (weeks 47-130): Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily for 5 consecutive days on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1.

Patients with CNS 3 disease or who are within 24 months of diagnosis with an initial WBC ≥ 100,000/mm^3 undergo whole brain radiotherapy (omit or discontinue mercaptopurine and IT methotrexate) on day 1. Testicular radiotherapy also begins on day 1.

Patients may receive oral methotrexate on day 1 of each course (if IT methotrexate is not administered).

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

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 3.1 years.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of B-cell precursor acute lymphoblastic leukemia

    • Registered on POG-9900 Classification Study
  • Registered within 7 days of documenting complete response after induction on day 29 or, if 2 more weeks of induction are required, no later than day 49
  • Classified as high risk:

    • No simultaneous trisomy 4 and 10
    • No TEL-AML1 gene
    • Meets criteria for 1 of the following:

      • Any age with WBC > 100,000/mm^3

        • CNS and bone marrow evaluations required for those patients with WBC > 100,000/mm^3 who are within 24 months of initial diagnosis
      • Age over 12 (boys) or 16 (girls)
      • If younger, WBC must be 1 of the following:

        • Greater than 80,000/mm^3 (for boys age 8 or girls age 12)
        • Greater than 60,000/mm^3 (for boys age 9 or girls age 13)
        • Greater than 40,000/mm^3 (for boys age 10 or girls age 14)
        • Greater than 20,000/mm^3 (for boys age 11 or girls age 15)
    • At least one of the following:

      • CNS 3 disease (CSF WBC at least 5/microliter with blasts present)
      • Testicular leukemia
      • MLL gene rearrangements

PATIENT CHARACTERISTICS:

Age:

  • 1 to 21

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Not specified

Renal:

  • Not specified

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • See Disease Characteristics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005603

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, United States, 94304
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0128
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, New York
Albert Einstein Clinical Cancer Center
Bronx, New York, United States, 10461
Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
United States, Ohio
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45229-3039
United States, Oregon
Doernbecher Children's Hospital
Portland, Oregon, United States, 97201-3098
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0361
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: William P. Bowman, MD Cook Children's Medical Center - Fort Worth
  More Information

Additional Information:
Publications:
Mullighan CG, Morin R, Zhang J, et al.: Next generation transcriptomic resequencing identifies novel genetic alterations in high-risk (HR) childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG) HR ALL TARGET Project. [Abstract] Blood 114 (22): A-704, 2009.
Zhang J, Mullighan CG, Harvey RC, et al.: Mutations in the RAS signaling, B-cell development, TP53/RB1, and JAK signaling pathways are common in high risk B-precursor childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG) High-Risk (HR) ALL TARGET Project. [Abstract] Blood 114 (22): A-85, 2009.
Harvey RC, Davidson GS, Wang X, et al.: Expression profiling identifies novel genetic subgroups with distinct clinical features and outcome in high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL). A Children's Oncology Group study. [Abstract] Blood 110 (11): A-1430, 2007.
Kang H, Bedrick EJ, Chen IM, et al.: Molecular classifiers for prediction of minimal residual disease (MRD) and event free survival (EFS) improve risk assignment at diagnosis in pediatric high-risk B precursor acute lymphoblastic leukemia (ALL): a Childrens Oncology Group study. [Abstract] Blood 110 (11): A-1422, 2007.
Borowitz MJ, Devidas M, Bowman WP, et al.: Prognostic significance of minimal residual disease (MRD) in children with high risk acute lymphoblastic leukemia(ALL): a Children's Oncology Group study. [Abstract] Blood 106 (11): A-85, 2005.
Borowitz MJ, Devidas M, Hunger SP, et al.: Prognostic signficance of end consolidation minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG). [Abstract] J Clin Oncol 26 (Suppl 15): A-10000, 2008.
Harvey RC, Chen IM, Ar K, et al.: Identification of novel cluster groups in high-risk pediatric B-precursor acute lymphoblastic leukemia (HR-ALL) by gene expression profiling: correlation with clinical and outcome variables a Children's Oncology Group (COG) study. [Abstract] Blood 112 (11): A-2256, 2008.
Yang JJ, Yang W, Cheng C, et al.: Genetically defined racial differences underlie risk of relapse in childhood acute lymphoblastic leukemia. [Abstract] Blood 112 (11): A-14, 2008.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00005603     History of Changes
Other Study ID Numbers: 9906, COG-P9906, POG-9906, CDR0000067722
Study First Received: May 2, 2000
Last Updated: February 18, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood acute lymphoblastic leukemia in remission
B-cell childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
Cyclophosphamide
Daunorubicin
Dexamethasone
Doxorubicin
Liposomal doxorubicin
Methotrexate
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on November 25, 2014