Combination Chemotherapy Plus PSC-833 in Treating Children With Refractory or Relapsed Acute Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00002912
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I mitoxantrone hydrochloride 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. Arm I etoposide 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. Arm I valspodar 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.
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (55)
Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Simmons Cancer Center - Dallas
🇺🇸Dallas, Texas, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Children's Memorial Hospital, Chicago
🇺🇸Chicago, Illinois, United States
Boston Floating Hospital Infants and Children
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States
City of Hope National Medical Center
🇺🇸Los Angeles, California, United States
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
🇺🇸Chicago, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
State University of New York - Upstate Medical University
🇺🇸Syracuse, New York, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Children's Hospital of Orange County
🇺🇸Orange, California, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Florida Health Science Center
🇺🇸Gainesville, Florida, United States
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Montreal Children's Hospital
🇨🇦Montreal, Quebec, Canada
Johns Hopkins Oncology Center
🇺🇸Baltimore, Maryland, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
UCSF Cancer Center and Cancer Research Institute
🇺🇸San Francisco, California, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
University of Minnesota Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Children's Hospital Medical Center - Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt Cancer Center
🇺🇸Nashville, Tennessee, United States
Texas Children's Cancer Center
🇺🇸Houston, Texas, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of California San Diego Cancer Center
🇺🇸La Jolla, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Columbia Presbyterian Hospital
🇺🇸New York, New York, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center
🇺🇸New York, New York, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital of Columbus
🇺🇸Columbus, Ohio, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States