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

NCT00002912 | Completed Phase 1

• 4 other identifiers: NCI-2012-01835POG-9423CCG-P9423CDR0000065285
• Study Type: interventional
• Target: 3
• Locations: 3 countries
• Sites: 55

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.

Conditions

Leukemia

Keywords

recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia

Study Arms (1)

Arm I

EXPERIMENTAL

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: etoposide; Drug: mitoxantrone hydrochloride; Drug: valspodar

Interventions

etoposide DRUG

Arm I

mitoxantrone hydrochloride DRUG

Arm I

valspodar DRUG

Arm I

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (55)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California San Diego Cancer Center

La Jolla, California, 92093-0658, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

City of Hope National Medical Center

Los Angeles, California, 91010, United States

Location

Children's Hospital of Orange County

Orange, California, 92668, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94115-0128, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5408, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

University of Florida Health Science Center

Gainesville, Florida, 32610-0296, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, 60611, United States

Location

Children's Memorial Hospital, Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5265, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231, United States

Location

Boston Floating Hospital Infants and Children

Boston, Massachusetts, 02111, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0752, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Columbia Presbyterian Hospital

New York, New York, 10032, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Columbus

Columbus, Ohio, 43205-2696, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73190, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

Vanderbilt Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Simmons Cancer Center - Dallas

Dallas, Texas, 75235-9154, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030-2399, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (2)

• 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.

  PMID: 20209646 RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Etoposide; Mitoxantrone; valspodar

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones

Study Officials

• Gary V.H. Dahl, MD

  Lucile Packard Children's Hospital at Stanford University Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: April 29, 2004
• Study Start: January 1, 1997
• Primary Completion: March 1, 2006
• Last Updated: February 1, 2013

Record last verified: 2010-08

Locations

US (50); AU (2); CA (3)