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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 1
N/A
21 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

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

Principal Investigator

Gary V.H. Dahl, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Lucile Packard Children's Hospital at Stanford University Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01835

NCT ID:

NCT00002912

Start Date:

January 1997

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • Leukemia

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Stanford University Medical CenterStanford, California  94305-5408
Emory University Hospital - AtlantaAtlanta, Georgia  30322
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
Johns Hopkins Oncology CenterBaltimore, Maryland  21287
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Simmons Cancer Center - DallasDallas, Texas  75235-9154
Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityChicago, Illinois  60611
Children's Hospital of MichiganDetroit, Michigan  48201
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
University of California San Diego Cancer CenterLa Jolla, California  92093-0658
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
State University of New York - Upstate Medical UniversitySyracuse, New York  13210
Vanderbilt Cancer CenterNashville, Tennessee  37232-6838
NYU School of Medicine's Kaplan Comprehensive Cancer CenterNew York, New York  10016
Boston Floating Hospital Infants and ChildrenBoston, Massachusetts  02111
University of Florida Health Science CenterGainesville, Florida  32610-0296
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
University of Kansas Medical CenterKansas City, Kansas  66160-7353
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital Medical Center - CincinnatiCincinnati, Ohio  45229-3039
Children's Hospital of ColumbusColumbus, Ohio  43205-2696
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Texas Children's Cancer CenterHouston, Texas  77030-2399
Columbia Presbyterian HospitalNew York, New York  10032
Children's Memorial Hospital, ChicagoChicago, Illinois  60614
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
City of Hope National Medical CenterLos Angeles, California  91010