Combination Chemotherapy Plus PSC-833 in Treating Children With Refractory or Relapsed Acute Leukemia

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

A PHASE I COOPERATIVE AGREEMENT PEDIATRIC TRIAL OF MITOXANTRONE, ETOPOSIDE AND PSC-833 (PSC-ME) THERAPY IN PATIENTS WITH RELAPSED AND REFRACTORY ACUTE LEUKEMIA

Phase I trial to study the effectiveness of PSC-833 plus etoposide and mitoxantrone in treating children who have refractory or relapsed acute leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Some cancers become resistant to chemotherapy drugs. Combining PSC-833 with chemotherapy may reduce resistance to the drug and allow more cancer cells to be killed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of PSC-833 in combination with mitoxantrone and etoposide in children with refractory or relapsed acute leukemia.

II. Determine the effects of PSC-833 on mitoxantrone and etoposide pharmacokinetics.

III. Quantify MDR1 gene expression and MDR1 P-glycoprotein expression and function in patient-derived leukemia cells.

OUTLINE: This is a dose escalation study of PSC-833.

Patients undergo induction therapy consisting of etoposide IV and mitoxantrone IV on days 1-5. Patients then receive PSC-833 IV over 124 hours beginning on day 2. A second course is administered no sooner than 21 days from the start of the first course if the marrow is hypocellular after the first course. Patients with persistent disease after 2 induction courses are removed from the study. Patients receive a total of 3 courses of etoposide/mitoxantrone. Patients who achieve complete remission after 1 induction course receive 2 courses of etoposide/mitoxantrone with PSC-833 as consolidation, beginning within 4 weeks of attainment of complete remission. Patients who achieve complete remission after 2 induction courses receive 1 course of etoposide/mitoxantrone with PSC-833 as consolidation. Cohorts of 3-6 patients receive escalating doses of PSC-833 until the maximum tolerated dose is determined. Patients are followed every 6 months.

Study Type

Interventional

Enrollment (Actual)

3

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
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
  • United States
    • 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
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 91010
        • City of Hope National Medical Center
      • Orange, California, United States, 92668
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94115-0128
        • UCSF Cancer Center and Cancer Research Institute
      • Stanford, California, United States, 94305-5408
        • Stanford University Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of Florida Health Science Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital, Chicago
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5265
        • Indiana University Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • University of Kansas Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • 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
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0752
        • University of Michigan Comprehensive Cancer Center
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • 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
        • 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
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute of New Jersey
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • 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
        • Columbia Presbyterian Hospital
      • Syracuse, New York, United States, 13210
        • State University of New York - Upstate Medical University
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Children's Hospital Medical Center - Cincinnati
      • Columbus, Ohio, United States, 43205-2696
        • Children's Hospital of Columbus
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73190
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt Cancer Center
    • Texas
      • Dallas, Texas, United States, 75235-9154
        • Simmons Cancer Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center
      • San Antonio, Texas, United States, 78284-7811
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Medical Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • 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

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Acute myeloid leukemia (AML) in one of the following categories:
  • First relapse if initial CR less than 6 months
  • Refractory to first or second induction with daunomycin, cytarabine, and thioguanine (DAT) or other anthracycline-containing regimens
  • Relapse following bone marrow transplantation provided good trilineage engraftment followed transplant and greater than 6 months since transplant
  • Presentation with secondary AML or AML evolving from myelodysplastic syndrome --Acute lymphocytic leukemia in one of the following categories:
  • In second or subsequent relapse or failed second or later induction attempts regardless of prior remissions
  • Relapsed following bone marrow transplantation provided good trilineage engraftment followed transplant and greater than 6 months since transplant
  • No isolated CNS or extramedullary relapse

PATIENT CHARACTERISTICS:

  • Age: Under 22 at diagnosis
  • Performance status: Karnofsky 50-100% (ECOG 0-2)
  • Lansky 40-100% (in patients under 12 years of age)
  • Life expectancy: At least 8 weeks
  • Bilirubin less than 1.5 mg/dL
  • ALT less than twice normal
  • Creatinine normal for age (within 2 standard deviations) OR glomular filtration rate at least 70 mL/min
  • Albumin at least 3 g/dL
  • Ejection fraction greater than 50% at rest or with 5% increase with exercise OR shortening fraction greater than 27% by echocardiogram
  • No history of clinical heart failure
  • No uncontrolled infection
  • No anticonvulsant therapy
  • No history of allergic reactions or anaphylaxis to etoposide not remediable by premedication
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Third percentile weight for height

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since chemotherapy and recovered
  • Prior cumulative anthracycline dose no greater than 360 mg per square meter
  • Hydroxyurea therapy allowed just prior to study for rapidly rising blast count

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
Patients undergo induction therapy consisting of etoposide IV and mitoxantrone IV on days 1-5. Patients then receive PSC-833 IV over 124 hours beginning on day 2. A second course is administered no sooner than 21 days from the start of the first course if the marrow is hypocellular after the first course. Patients with persistent disease after 2 induction courses are removed from the study. Patients receive a total of 3 courses of etoposide/mitoxantrone. Patients who achieve complete remission after 1 induction course receive 2 courses of etoposide/mitoxantrone with PSC-833 as consolidation, beginning within 4 weeks of attainment of complete remission. Patients who achieve complete remission after 2 induction courses receive 1 course of etoposide/mitoxantrone with PSC-833 as consolidation. Cohorts of 3-6 patients receive escalating doses of PSC-833 until the maximum tolerated dose is determined. Patients are followed every 6 months.
Drug: mitoxantrone hydrochloride
Drug: etoposide
Drug: valspodar

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Gary V.H. Dahl, MD, Lucile Packard Children's Hospital at Stanford University Medical Center

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, 1997

Primary Completion (Actual)

March 1, 2006

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

April 28, 2004

First Posted (Estimate)

April 29, 2004

Study Record Updates

Last Update Posted (Estimate)

February 1, 2013

Last Update Submitted That Met QC Criteria

January 31, 2013

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01835
  • POG-9423
  • CCG-P9423
  • CDR0000065285 (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.

Clinical Trials on Leukemia

Clinical Trials on mitoxantrone hydrochloride

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cambodia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe