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Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma
This study has been completed.
First Received: July 11, 2001   Last Updated: December 13, 2008   History of Changes
Sponsor: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00020111
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide in treating young patients with leukemia or lymphoma.


Condition Intervention Phase
Leukemia
Lymphoma
Drug: arsenic trioxide
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: March 2000
Detailed Description:

OBJECTIVES:

  • Determine the toxic effects of arsenic trioxide in pediatric patients with refractory leukemia or lymphoma.
  • Determine the maximum tolerated dose of this drug in this patient population.
  • Determine the plasma pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease (acute promyelocytic leukemia [APL] vs non-APL).

  • Stratum I (APL patients): Patients receive standard-dose arsenic trioxide IV over 2 hours daily 5 days a week for 4 weeks. Treatment continues every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
  • Stratum II (Non-APL patients): Cohorts of 3-6 patients receive escalating doses of arsenic trioxide (according to the stratum 1 schedule above) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with arsenic trioxide at the recommended phase II dose.

Leukemia patients in both strata without progressive disease who have not achieved complete remission after the first 20 doses may continue to receive arsenic trioxide for 2 additional weeks.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for stratum I of this study within 2-3 years. A total of 3-30 patients will be accrued for stratum II of this study within 1-2 years.

  Eligibility

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed leukemia or lymphoma refractory to standard curative treatment regimens
  • Measurable or evaluable disease
  • No meningeal leukemia or lymphoma
  • No HIV-related lymphoma
  • No lymphoproliferative diseases

PATIENT CHARACTERISTICS:

Age:

  • 2 to 21

    • Acute promyelocytic leukemia (APL) patients (stratum I) must be age 2 to 12

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin normal
  • SGPT less than 2 times upper limit of normal
  • No significant hepatic dysfunction that would preclude study therapy

Renal:

  • Creatinine normal (age adjusted) OR
  • Creatinine clearance at least 60 mL/min
  • Potassium, magnesium, and calcium at least lower limit of normal (oral or IV supplementation allowed)
  • No significant renal dysfunction that would preclude study therapy

Cardiovascular:

  • Rate corrected QTc interval no greater than 0.48 on EKG
  • No significant cardiac dysfunction that would preclude study therapy
  • No cardiac disease, including dysrhythmias

Pulmonary:

  • No significant pulmonary dysfunction that would preclude study therapy

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No persistent grade 3 or greater sensory or motor neuropathy
  • No prior grand mal seizures (grade 3 or greater) within the past 2 years other than febrile seizures (except for patients with APL at discretion of investigator)
  • No clinically significant unrelated systemic illness that would preclude study therapy (e.g., serious infection)
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], and epoetin alfa)
  • No concurrent immunotherapy

Chemotherapy:

  • No prior arsenic trioxide
  • At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
  • No concurrent intrathecal chemotherapy except for acute promyelocytic leukemia (APL) patients experiencing progressive meningeal leukemia and demonstrating benefit from arsenic trioxide for systemic disease
  • No other concurrent anticancer chemotherapy

Endocrine therapy:

  • No concurrent steroids (except corticosteroids for retinoic acid syndrome)

Radiotherapy:

  • At least 4 weeks since prior radiotherapy and recovered
  • No concurrent radiotherapy

Surgery:

  • Not specified

Other:

  • At least 6 months since prior anticonvulsants
  • At least 1 week since prior retinoid therapy
  • No concurrent retinoids
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00020111

  Hide Study Locations
Locations
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Children's Hospital of Orange County
Orange, California, United States, 92868
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
County of Los Angeles Harbor-UCLA Medical Center
Torrance, California, United States, 90509
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92103-8447
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Atlanta, Georgia, United States, 30342
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202-5225
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Floating Hospital for Children
Boston, Massachusetts, United States, 02111
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0914
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, Missouri
Cardinal Glennon Children's Hospital
Saint Louis, Missouri, United States, 63104
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-2899
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
Cleveland, Ohio, United States, 44106-5065
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73126
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, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105-2794
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232-6310
United States, Texas
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
MD Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9063
Texas Children's Cancer Center
Houston, Texas, United States, 77030-2399
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7811
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, Wisconsin
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, Victoria
Royal Children's Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Sponsors and Collaborators
Investigators
Study Chair: Frank M. Balis, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000067717, NCI-00-C-0070J, NCI-T99-0080
Study First Received: July 11, 2001
Last Updated: December 13, 2008
ClinicalTrials.gov Identifier: NCT00020111     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute myeloid leukemia
childhood acute promyelocytic leukemia (M3)
recurrent childhood acute lymphoblastic leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia

Additional relevant MeSH terms:
Lymphatic Diseases
Leukemia
Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Arsenic trioxide
Lymphoproliferative Disorders
Lymphoma
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009