Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

NCT00002744 | Completed Phase 3 DMC

• 3 other identifiers: 1952CCG-1952CDR0000064665
• Study Type: interventional
• Target: 1,970
• Locations: 3 countries
• Sites: 34

Brief Summary

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 giving them in different ways may kill more cancer cells. It is not yet known which regimen of combination chemotherapy is more effective for acute lymphoblastic leukemia PURPOSE: Randomized phase III trial to compare different regimens of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

untreated childhood acute lymphoblastic leukemia; L1 childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Event Free Survival

  Primary outcome index used in examining the randomized treatment groups will be event-free survival (EFS) from the time of randomization (i.e., end of Induction), where the life table events will consist of the first occurrence of leukemic relapse at any site, death, or occurrence of a second malignancy.

Secondary Outcomes (1)

• Comparisons of CNS relapse incidence rates

Study Arms (4)

Arm I

EXPERIMENTAL

Therapy defined in description.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET photon therapy

Arm 2

EXPERIMENTAL

Therapy defined in description.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET photon therapy

Arm 3

EXPERIMENTAL

Therapy defined in description.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET photon therapy

Arm 4

EXPERIMENTAL

Therapy defined in description.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET photon therapy

Interventions

asparaginase DRUG

Also known as: L-Asparaginase - Erwinia, NSC-106977

Arm 2; Arm 3; Arm 4; Arm I

cyclophosphamide DRUG

Also known as: Cytoxan, NSC-26271.

Arm 2; Arm 3; Arm 4; Arm I

cytarabine DRUG

Also known as: Cytosine Arabinoside, Ara-C, Cytosar-U

Arm 2; Arm 3; Arm 4; Arm I

daunorubicin hydrochloride DRUG

Also known as: NSC-82151

Arm 2; Arm 3; Arm 4; Arm I

dexamethasone DRUG

Also known as: Decadron, NSC-34521

Arm 2; Arm 3; Arm 4; Arm I

doxorubicin hydrochloride DRUG

Also known as: Adriamycin, NSC-123127

Arm 2; Arm 3; Arm 4; Arm I

mercaptopurine DRUG

Also known as: 6-MP, Purinethol

Arm 2; Arm 3; Arm 4; Arm I

methotrexate DRUG

Also known as: NSC-740

Arm 2; Arm 3; Arm 4; Arm I

pegaspargase DRUG

Also known as: PEG Asparaginase, Oncaspar®

Arm 2; Arm 3; Arm 4; Arm I

prednisone DRUG

Also known as: NSC-10023

Arm 2; Arm 3; Arm 4; Arm I

therapeutic hydrocortisone DRUG

Arm 2; Arm 3; Arm 4; Arm I

thioguanine DRUG

Also known as: 6-TG, NSC-752

Arm 2; Arm 3; Arm 4; Arm I

vincristine sulfate DRUG

Also known as: Oncovin, NSC-67574

Arm 2; Arm 3; Arm 4; Arm I

low-LET cobalt-60 gamma ray therapy RADIATION

Arm 2; Arm 3; Arm 4; Arm I

low-LET photon therapy RADIATION

Arm 2; Arm 3; Arm 4; Arm I

Eligibility Criteria

• Age: 1 Year - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

DISEASE CHARACTERISTICS: Newly diagnosed acute lymphoblastic leukemia (ALL) obtained by bone marrow aspirate or bone marrow biopsy No greater than 25% L3 blasts Initial white blood cell count less than 50,000/mm3 (performed at CCG institution) Massive lymphadenopathy, massive splenomegaly, and/or large mediastinal mass allowed CNS or testicular leukemia allowed Allogeneic bone marrow transplant should be considered (if donor available) for patients with Philadelphia chromosome (t\[9;22\]\[q34;q11\]) or translocation (4;11)(q21;q23) PATIENT CHARACTERISTICS: Age: 1 through 9 Performance status: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified PRIOR CONCURRENT THERAPY: No prior treatment for ALL Biologic therapy: Not specified Chemotherapy: Intrathecal cytarabine (IT ARA-C) may begin prior to registration provided systemic chemotherapy initiated within 72 hours after IT ARA-C Endocrine therapy: See Radiotherapy At least 1 month since prior systemic steroids Steroids given for less than 48 hours allowed Inhaled corticosteroids allowed at any time Radiotherapy: Radiotherapy or dexamethasone for mediastinal mass causing superior mediastinal syndrome allowed prior to registration, if indicated Surgery: Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (34)

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital of Orange County

Orange, California, 92668, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94115-0128, United States

Location

Children's Hospital of Denver

Denver, Colorado, 80218, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5265, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0752, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, 64108, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-3330, United States

Location

Kaplan Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, 27599-7295, United States

Location

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Ireland Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Children's Hospital of Columbus

Columbus, Ohio, 43205-2696, United States

Location

Doernbecher Children's Hospital

Portland, Oregon, 97201-3098, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital and Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

IWK Grace Health Centre

Halifax, Nova Scotia, B3J 3G9, Canada

Location

Related Publications (12)

• Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008 Dec;22(12):2142-50. doi: 10.1038/leu.2008.251. Epub 2008 Sep 25.

  PMID: 18818707 BACKGROUND

• Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.

  BACKGROUND

• Stork LC, Matloub Y, Broxson E, La M, Yanofsky R, Sather H, Hutchinson R, Heerema NA, Sorrell AD, Masterson M, Bleyer A, Gaynon PS. Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial. Blood. 2010 Apr 8;115(14):2740-8. doi: 10.1182/blood-2009-07-230656. Epub 2010 Feb 1.

  PMID: 20124218 RESULT

• Kadan-Lottick NS, Brouwers P, Breiger D, Kaleita T, Dziura J, Northrup V, Chen L, Nicoletti M, Bostrom B, Stork L, Neglia JP. Comparison of neurocognitive functioning in children previously randomly assigned to intrathecal methotrexate compared with triple intrathecal therapy for the treatment of childhood acute lymphoblastic leukemia. J Clin Oncol. 2009 Dec 10;27(35):5986-92. doi: 10.1200/JCO.2009.23.5408. Epub 2009 Nov 2.

  PMID: 19884541 RESULT

• Malempati S, Gaynon PS, Sather H, La MK, Stork LC; Children's Oncology Group. Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Children's Oncology Group study CCG-1952. J Clin Oncol. 2007 Dec 20;25(36):5800-7. doi: 10.1200/JCO.2007.10.7508.

  PMID: 18089878 RESULT

• Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC; Children's Oncology Group. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. Blood. 2006 Aug 15;108(4):1165-73. doi: 10.1182/blood-2005-12-011809. Epub 2006 Apr 11.

  PMID: 16609069 RESULT

• Bassal M, La MK, Whitlock JA, Sather HN, Heerema NA, Gaynon PS, Stork LC. Lymphoblast biology and outcome among children with Down syndrome and ALL treated on CCG-1952. Pediatr Blood Cancer. 2005 Jan;44(1):21-8. doi: 10.1002/pbc.20193.

  PMID: 15368546 RESULT

• Malempati S, Gaynon PS, Sather H, et al.: Outcome after relapse among children with standard risk (SR) ALL treated on CCG-1952. [Abstract] Blood 104 (11): A-520, 2004.

  RESULT

• Stork LC, Sather H, Hutchinson RJ, et al.: Comparison of mercaptopurine (MP) with thioguanine (TG) and IT methotrexate (ITM) with IT "triples" (ITT) in children with SR-ALL: results of CCG-1952. [Abstract] Blood 100 (11 Pt 1): A-585, 156a, 2002.

  RESULT

• Stork LC, Sather H, Yanofsky R, et al.: Hyperdiploidy with trisomy 10 and TEL-AML1 expression among children with standard risk acute lymphoblastic leukemia (SR-ALL): a CCG-1952 report. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1476, 2001.

  RESULT

• Gaynon PS, Stork L, Sather H, et al.: Leukemic progenitor cell content of pre- and post-induction chemotherapy bone marrow specimens from children with newly diagnosed or relapsed acute lymphoblastic leukemia (ALL). [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-2187, 567a, 1999.

  RESULT

• Stork LC, Erdmann G, Adamson P, et al.: Oral 6-thioguanine causes relatively mild and reversible hepatic veno-occlusive disease(VOD). J Pediatr Hematol Oncol 20: 400a, 1998.

  RESULT

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Asparaginase; asparaginase erwinia chrysanthemi recombinant; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Calcium Dobesilate; Doxorubicin; Mercaptopurine; Methotrexate; pegaspargase; Prednisone; Hydrocortisone; Thioguanine; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Sulfhydryl Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Pregnadienediols; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Linda C. Stork, MD

  Doernbecher Children's Hospital at Oregon Health and Science University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: September 1, 2004
• Study Start: May 1, 1996
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: February 9, 2017

Record last verified: 2014-07

Locations

US (31); AU (1); CA (2)