Combination Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia

NCT00002816 | Completed Phase 3 DMC

• 3 other identifiers: 1951CCG-1951CDR0000064968
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 33

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase III trial to compare the effectiveness of combination chemotherapy in treating children who have relapsed acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

recurrent childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Event Free Survival

  The evaluation of the relationship between prognostic or treatment factors and EFS

Study Arms (2)

EARLY # CNS RELAPSE with BM DONOR

EXPERIMENTAL

Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.

Drug: cytarabine; Drug: dexamethasone; Drug: etoposide; Drug: idarubicin; Drug: ifosfamide; Drug: leucovorin calcium; Drug: mesna; Drug: pegaspargase; Drug: therapeutic hydrocortisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy; Drug: Methotrexate

LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

EXPERIMENTAL

Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.

Drug: cytarabine; Drug: dexamethasone; Drug: etoposide; Drug: idarubicin; Drug: ifosfamide; Drug: leucovorin calcium; Drug: mesna; Drug: pegaspargase; Drug: therapeutic hydrocortisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy; Drug: Methotrexate

Interventions

cytarabine DRUG

Given IV

Also known as: Cytosine Arabinoside, Ara-C, Cytosar-U, NSC-63878

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

dexamethasone DRUG

Given IV

Also known as: Decadron, NSC- 34521

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

etoposide DRUG

Given IV

Also known as: VP-16, VePesid, NSC-14154p

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

idarubicin DRUG

Given IV

Also known as: Idamycin, NSC-256439

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

ifosfamide DRUG

Given IV

Also known as: Ifex, NSC-109724

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

leucovorin calcium DRUG

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

mesna DRUG

Given IV

Also known as: Mesnex, NSC-113891

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

pegaspargase DRUG

Given IV

Also known as: PEG Asparaginase, PEG-ASP, K/H, KYOWA, HAKKO, NSC-644954

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

therapeutic hydrocortisone DRUG

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

thioguanine DRUG

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

vincristine sulfate DRUG

Given IV

Also known as: Oncovin, NSC-675574

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

low-LET cobalt-60 gamma ray therapy RADIATION

LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

low-LET electron therapy RADIATION

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

low-LET photon therapy RADIATION

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

Methotrexate DRUG

Given IV

Also known as: MTX, NSC-740

EARLY # CNS RELAPSE with BM DONOR; LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: Acute lymphoblastic leukemia (ALL) with isolated extramedullary relapse Relapse occurred during or following front-line therapy for ALL Initial diagnosis of more than 25% blasts of L1 or L2 morphology No leukemic marrow (M1) by conventional assessment Patients with B precursor ALL must also be enrolled on study CCG-B958 Relapse occurred in the CNS, testis, or eye Ocular relapse confirmed by an ophthalmologist and by cytology or iris biopsy Combined CNS and ocular relapse eligible Down Syndrome patients not eligible No prior bone marrow transplantation in first remission No prior toxicity from any study drugs Patient age: Under 21 PATIENT CHARACTERISTICS: See General Eligibility Criteria

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 (33)

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

Huntsman Cancer Institute

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital and Regional 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 (2)

• Uckun FM, Gaynon PS, Stram DO, Sensel MG, Sarquis MB, Willoughby M. Bone marrow leukemic progenitor cell content in pediatric T-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse. Leuk Lymphoma. 2001 Jan;40(3-4):279-85. doi: 10.3109/10428190109057926.

  PMID: 11426549 RESULT

• Uckun FM, Gaynon PS, Stram DO, Sensel MG, Sarquis MB, Lazarus KH, Willoughby M. Paucity of leukemic progenitor cells in the bone marrow of pediatric B-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse. Clin Cancer Res. 1999 Sep;5(9):2415-20.

  PMID: 10499612 RESULT

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cytarabine; Dexamethasone; Calcium Dobesilate; Etoposide; Idarubicin; Ifosfamide; Leucovorin; Mesna; pegaspargase; Hydrocortisone; Thioguanine; Vincristine; Methotrexate

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)

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

Study Officials

• Michael L.N. Willoughby, MD

  Princess Margaret Hospital for Children

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: June 23, 2004
• Study Start: December 1, 1996
• Primary Completion: November 1, 2002
• Study Completion: April 1, 2006
• Last Updated: August 22, 2013

Record last verified: 2013-08

Locations

AU (1); CA (2); US (30)