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

NCT ID: NCT00002912

Last Updated: 2013-02-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-01-31

Brief Summary

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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

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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.

Conditions

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Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

etoposide

Intervention Type DRUG

mitoxantrone hydrochloride

Intervention Type DRUG

valspodar

Intervention Type DRUG

Interventions

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etoposide

Intervention Type DRUG

mitoxantrone hydrochloride

Intervention Type DRUG

valspodar

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gary V.H. Dahl, MD

Role: STUDY_CHAIR

Lucile Packard Children's Hospital at Stanford University Medical Center

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

City of Hope National Medical Center

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Florida Health Science Center

Gainesville, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Site Status

Children's Memorial Hospital, Chicago

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

Boston Floating Hospital Infants and Children

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Columbia Presbyterian Hospital

New York, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Texas Children's Cancer Center

Houston, Texas, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Australia Canada

References

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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: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 May;54(5):694-702. doi: 10.1002/pbc.22366.

Reference Type RESULT
PMID: 20209646 (View on PubMed)

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 Society of Clinical Oncology 21: A-1583, 2002.

Reference Type RESULT

Other Identifiers

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POG-9423

Identifier Type: -

Identifier Source: secondary_id

CCG-P9423

Identifier Type: -

Identifier Source: secondary_id

CDR0000065285

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01835

Identifier Type: -

Identifier Source: org_study_id

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