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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002912
• Other study ID #: NCI-2012-01835
• Secondary ID: POG-9423CCG-P942
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: January 31, 2013
• Start date: January 1997

Study information

• Verified date: August 2010
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 3
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

Drug:
• etoposide

• mitoxantrone hydrochloride

• valspodar

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Health Science Center	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Texas Children's Cancer Center	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego Cancer Center	La Jolla	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	City of Hope National Medical Center	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Columbia Presbyterian Hospital	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (2)

Lacayo NJ, Lum BL, Chin DL, et al.: Pharmacokinetics of mitoxantrone in a Phase I Trial of PSC-833 (Valspodar) as an MDR1/Pg-P modulator in acute myeloid leukemia (AML) from the children's oncology group (COG). [Abstract] Proceedings of the American Socie

O'Brien MM, Lacayo NJ, Lum BL, Kshirsagar S, Buck S, Ravindranath Y, Bernstein M, Weinstein H, Chang MN, Arceci RJ, Sikic BI, Dahl GV. Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia — View Citation