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

January 31, 2013 updated by: National Cancer Institute (NCI)

TREATMENT OF ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA -- A PEDIATRIC ONCOLOGY GROUP-WIDE PHASE II STUDY

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

156

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
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster Division
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
  • Puerto Rico
      • San Juan, Puerto Rico, 00936-5067
        • University of Puerto Rico School of Medicine Medical Sciences Campus
  • Switzerland
      • Bern, Switzerland, CH 3010
        • Swiss Pediatric Oncology Group Bern
      • Geneva, Switzerland, 1211
        • Clinique de Pediatrie
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University Of Alabama Comprehensive Cancer Center
      • Mobile, Alabama, United States, 36688
        • MBCCOP - University of South Alabama
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • La Jolla, California, United States, 92093-0658
        • University of California San Diego Cancer Center
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital at Stanford
      • Sacramento, California, United States, 95817
        • University of California Davis Medical Center
      • San Diego, California, United States, 92123-4282
        • Children's Hospital and Health Center
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8028
        • Yale Comprehensive Cancer Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20307-5000
        • Walter Reed Army Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610-100277
        • Shands Hospital and Clinics, University of Florida
      • Miami, Florida, United States, 33136
        • Sylvester Cancer Center, University of Miami
      • Miami, Florida, United States, 33155
        • Miami Children's Hospital
      • Tampa, Florida, United States, 33682-7757
        • CCOP - Florida Pediatric
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital, Chicago
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • University Of Kansas Medical Center
      • Wichita, Kansas, United States, 67214-3882
        • CCOP - Wichita
      • Wichita, Kansas, United States, 67214
        • Via Christi Regional Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
      • New Orleans, Louisiana, United States, 70112
        • MBCCOP - LSU Medical Center
      • New Orleans, Louisiana, United States, 70121
        • CCOP - Ochsner
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Oncology Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Boston Floating Hospital Infants and Children
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Hackensack, New Jersey, United States, 07601
        • CCOP - Northern New Jersey
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • New Hyde Park, New York, United States, 11042
        • Schneider Children's Hospital
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • Rochester, New York, United States, 14642
        • University of Rochester Cancer Center
      • Stony Brook, New York, United States, 11790-9832
        • State University of New York Health Sciences Center - Stony Brook
      • Syracuse, New York, United States, 13210
        • State University of New York - Upstate Medical University
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Memorial Mission Hospital
      • Charlotte, North Carolina, United States, 28232-2861
        • Carolinas Medical Center
      • Charlotte, North Carolina, United States, 28233-3549
        • Presbyterian Healthcare
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Greenville, North Carolina, United States, 27858-4354
        • East Carolina University School of Medicine
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73126-0307
        • Oklahoma Memorial Hospital
    • Oregon
      • Portland, Oregon, United States, 97213
        • CCOP - Columbia River Program
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134-1095
        • St. Christopher's Hospital for Children
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Medical University of South Carolina
      • Greenville, South Carolina, United States, 29605
        • Children's Hospital of Greenville Hospital System
    • Tennessee
      • Memphis, Tennessee, United States, 38105-2794
        • Saint Jude Children's Research Hospital
    • Texas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Dallas, Texas, United States, 75235-9154
        • Simmons Cancer Center - Dallas
      • 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
      • San Antonio, Texas, United States, 78284-7811
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78284-7810
        • MBCCOP - South Texas Pediatric
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Cancer Center, University of Virginia HSC
      • Portsmouth, Virginia, United States, 23708-2197
        • Naval Medical Center, Portsmouth
      • Richmond, Virginia, United States, 23298-0037
        • Massey Cancer Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506-9162
        • West Virginia University Hospitals
    • Wisconsin
      • 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 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: cyclophosphamide
Drug: leucovorin calcium
Drug: asparaginase
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: etoposide
Drug: methotrexate
Drug: therapeutic hydrocortisone
Drug: thiotepa
Drug: vincristine sulfate
Drug: mercaptopurine
Biological: filgrastim
Drug: mesna
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy
Drug: liposomal cytarabine

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Julio C. Barredo, MD, Medical University of South Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

January 1, 1996

Primary Completion (Actual)

June 1, 2004

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

June 30, 2004

First Posted (Estimate)

July 1, 2004

Study Record Updates

Last Update Posted (Estimate)

February 1, 2013

Last Update Submitted That Met QC Criteria

January 31, 2013

Last Verified

November 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01528
  • POG-9412
  • CDR0000064509 (Registry Identifier: PDQ (Physician Data Query))

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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