Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma

April 28, 2015 updated by: National Cancer Institute (NCI)

Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

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

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital For Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital at McGill University Health Center
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • La Jolla, California, United States, 92103-8447
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital at Stanford University Medical Center
      • San Francisco, California, United States, 94143
        • UCSF Comprehensive Cancer Center
      • Torrance, California, United States, 90509
        • County of Los Angeles Harbor-UCLA Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5225
        • Riley Children Cancer Center at Riley Hospital for Children
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Floating Hospital for Children
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0914
        • University of Michigan Comprehensive Cancer Center
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • St. Louis Children's Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Cancer Center at Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center at Columbia University
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-2899
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44106-5065
        • Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73126
        • Oklahoma University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh
    • Tennessee
      • Memphis, Tennessee, United States, 38105-2794
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232-6310
        • Vanderbilt Children's Hospital
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center
      • Houston, Texas, United States, 77030-4009
        • MD Anderson Cancer Center at University of Texas
      • San Antonio, Texas, United States, 78284-7811
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute at University of Utah
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Comprehensive Cancer Center
      • 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

2 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Frank M. Balis, MD, National Cancer Institute (NCI)

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

March 1, 2000

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

April 29, 2015

Last Update Submitted That Met QC Criteria

April 28, 2015

Last Verified

February 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067717
  • NCI-00-C-0070J
  • NCI-T99-0080

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.

Clinical Trials on Lymphoma

Clinical Trials on arsenic trioxide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Chile

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe