Radiation Therapy and Chemotherapy in Treating Children With CNS Relapse From Acute Lymphoblastic Leukemia

NCT ID: NCT00002704

Last Updated: 2013-02-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

156 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Phase II trial to study the effectiveness of radiation therapy following chemotherapy in treating children with CNS relapse from acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more cancer cells.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

OBJECTIVES:

I. Determine the efficacy and toxicity of intensified systemic treatment with delayed central nervous system (CNS) irradiation in children with acute lymphoblastic leukemia and isolated CNS disease.

II. Determine the efficacy of systemic thiotepa in reducing or clearing blasts in the cerebrospinal fluid of these patients.

III. Evaluate the toxicity of single dose thiotepa followed by dexamethasone, vincristine, daunorubicin, and triple intrathecal therapy in these patients.

IV. Determine the response rate of intrathecal sustained release cytarabine (DTC101) in patients with first bone marrow remission with first isolated CNS relapse.

V. Assess the safety and toxicity of DTC101 in these patients.

OUTLINE:

Patients with significant neurologic symptoms (e.g., seizures, cranial nerve palsy, paresis, mental status changes) are entered directly on the Induction regimen and do not receive the Therapeutic Window. The following acronyms are used: ARA-C Cytarabine, NSC-63878 ASP Asparaginase, NSC-109229 (E. coli) or 106977 (Erwinia) CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 DM Dexamethasone, NSC-34521 DNR Daunorubicin, NSC-82151 DTC101 Sustained release cytarabine G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 HC Hydrocortisone, NSC-10483 Mesna Mercaptoethane sulfonate, NSC-113891 MP Mercaptopurine, NSC-755 MTX Methotrexate, NSC-740 TIT Triple Intrathecal Therapy, IT MTX/IT HC/IT ARA-C TMP-SMX Trimethoprim-sulfamethoxazole TSPA Thiotepa, NSC-6396 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540

THERAPEUTIC WINDOW: Single Agent Chemotherapy. TSPA or DTC101. \*\* Thiotepa window closed as of 7/6/98 \*\* \*\* DTC101 window opened 11/15/99 \*\*

INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT.

CONSOLIDATION: 2-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. ARA-C/ASP; plus TIT.

INTENSIFICATION I: 4-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. CTX/MP/MTX/VP-16; with CF; plus TIT.

RE-INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT.

INTENSIFICATION II: 6-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. ARA-C/ASP/CTX/MP/MTX/VP-16; with CF; plus TIT.

CHEMORADIOTHERAPY: Radiotherapy plus 3-Drug Combination Chemotherapy. Craniospinal irradiation using x-rays with energies of 4-6 MV (electrons acceptable for spinal cord irradiation); plus ASP/DM/VCR.

MAINTENANCE: 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination Chemotherapy. MP/MTX; alternating with CTX/VCR.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm I

Single Agent Chemotherapy. TSPA or DTC101. 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. 2-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. ARA-C/ASP; plus TIT. 4-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. CTX/MP/MTX/VP-16; with CF; plus TIT. 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. 6-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. ARA-C/ASP/CTX/MP/MTX/VP-16; with CF; plus TIT. Radiotherapy plus 3-Drug Combination Chemotherapy. Craniospinal irradiation using x-rays with energies of 4-6 MV (electrons acceptable for spinal cord irradiation); plus ASP/DM/VCR. 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination Chemotherapy. MP/MTX; alternating with CTX/VCR.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

asparaginase

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

daunorubicin hydrochloride

Intervention Type DRUG

dexamethasone

Intervention Type DRUG

etoposide

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

liposomal cytarabine

Intervention Type DRUG

mercaptopurine

Intervention Type DRUG

mesna

Intervention Type DRUG

methotrexate

Intervention Type DRUG

therapeutic hydrocortisone

Intervention Type DRUG

thiotepa

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

filgrastim

Intervention Type BIOLOGICAL

asparaginase

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

daunorubicin hydrochloride

Intervention Type DRUG

dexamethasone

Intervention Type DRUG

etoposide

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

liposomal cytarabine

Intervention Type DRUG

mercaptopurine

Intervention Type DRUG

mesna

Intervention Type DRUG

methotrexate

Intervention Type DRUG

therapeutic hydrocortisone

Intervention Type DRUG

thiotepa

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

low-LET electron therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

DISEASE CHARACTERISTICS:

* Acute lymphoblastic leukemia in first bone marrow remission (M1) with first isolated initial CNS relapse
* More than 5 WBC/microliter in cerebrospinal fluid (CSF) with blasts on cytospin OR immunophenotypic proof (encouraged) of relapse in CSF
* Identifiable blasts and presence on 2 CSF samples 3 weeks apart
* If B-cell terminal deoxynucleotidyl transferase (TdT) OR CD-10
* If T-cell TdT alone OR with CD-7

PATIENT CHARACTERISTICS:

* Age: Over 6 months and under 21 years at relapse
* Patients receiving sustained release cytarabine
* Performance status: Older than 10 years
* Karnofsky greater than 50% Less than 10 years
* Lansky greater than 50%
* Platelet count greater than 40,000/mm3
* Bilirubin less than 2.0 mg/dL
* SGPT less than 5 times normal
* Creatinine less than 1.5 times normal for age
* Normal metabolic parameters (serum electrolytes, calcium, and phosphorus)
* No clinical evidence of obstructive hydrocephalus, compartmentalization of the CSF flow, ventriculoperitoneal or ventriculoatrial shunt

PRIOR CONCURRENT THERAPY:

* Prior cumulative anthracycline dose less than 375 mg/sqm
* Patients receiving sustained release cytarabine
* At least 7 days since prior investigational drug
* At least 3 weeks since prior CNS directed therapy (6 weeks is prior nitrosourea)
* At least 1 week since intrathecal chemotherapy
* At least 8 weeks since prior craniospinal radiotherapy
Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Julio C. Barredo, MD

Role: STUDY_CHAIR

Medical University of South Carolina

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

MBCCOP - University of South Alabama

Mobile, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

Children's Hospital and Health Center

San Diego, California, United States

Site Status

Yale Comprehensive Cancer Center

New Haven, Connecticut, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

Shands Hospital and Clinics, University of Florida

Gainesville, Florida, United States

Site Status

Sylvester Cancer Center, University of Miami

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

CCOP - Florida Pediatric

Tampa, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Children's Memorial Hospital, Chicago

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

CCOP - Ochsner

New Orleans, Louisiana, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

Boston Floating Hospital Infants and Children

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Schneider Children's Hospital

New Hyde Park, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

University of Rochester Cancer Center

Rochester, New York, United States

Site Status

State University of New York Health Sciences Center - Stony Brook

Stony Brook, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Memorial Mission Hospital

Asheville, North Carolina, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Presbyterian Healthcare

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

East Carolina University School of Medicine

Greenville, North Carolina, United States

Site Status

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Oklahoma Memorial Hospital

Oklahoma City, Oklahoma, United States

Site Status

CCOP - Columbia River Program

Portland, Oregon, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Children's Hospital of Greenville Hospital System

Greenville, South Carolina, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

San Antonio Military Pediatric Cancer and Blood Disorders Center

Lackland Air Force Base, Texas, United States

Site Status

MBCCOP - South Texas Pediatric

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Cancer Center, University of Virginia HSC

Charlottesville, Virginia, United States

Site Status

Naval Medical Center, Portsmouth

Portsmouth, Virginia, United States

Site Status

Massey Cancer Center

Richmond, Virginia, United States

Site Status

West Virginia University Hospitals

Morgantown, West Virginia, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

McMaster Division

Hamilton, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

University of Puerto Rico School of Medicine Medical Sciences Campus

San Juan, , Puerto Rico

Site Status

Swiss Pediatric Oncology Group Bern

Bern, , Switzerland

Site Status

Clinique de Pediatrie

Geneva, , Switzerland

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada Puerto Rico Switzerland

References

Explore related publications, articles, or registry entries linked to this study.

Eapen M, Zhang MJ, Devidas M, Raetz E, Barredo JC, Ritchey AK, Godder K, Grupp S, Lewis VA, Malloy K, Carroll WL, Davies SM, Camitta BM; Children's Oncology Group; Center for International Blood and Marrow Transplant Research. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia. 2008 Feb;22(2):281-6. doi: 10.1038/sj.leu.2405037. Epub 2007 Nov 22.

Reference Type BACKGROUND
PMID: 18033318 (View on PubMed)

Barredo JC, Devidas M, Lauer SJ, Billett A, Marymont M, Pullen J, Camitta B, Winick N, Carroll W, Ritchey AK. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study. J Clin Oncol. 2006 Jul 1;24(19):3142-9. doi: 10.1200/JCO.2005.03.3373.

Reference Type RESULT
PMID: 16809737 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

POG-9412

Identifier Type: -

Identifier Source: secondary_id

CDR0000064509

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01528

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.