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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00002912




Registration number
NCT00002912
Ethics application status
Date submitted
1/11/1999
Date registered
29/04/2004
Date last updated
1/02/2013

Titles & IDs
Public title
Combination Chemotherapy Plus PSC-833 in Treating Children With Refractory or Relapsed Acute Leukemia
Scientific 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
Secondary ID [1] 0 0
POG-9423
Secondary ID [2] 0 0
NCI-2012-01835
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: 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.
Comparator / control treatment
Control group

Outcomes

Eligibility
Key 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
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/1997
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
6001 - Perth
Recruitment outside Australia
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United States of America
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Arkansas
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California
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District of Columbia
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Florida
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Georgia
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Illinois
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Indiana
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Kansas
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Washington
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Wisconsin
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Canada
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Ontario
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Canada
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Quebec

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00002912
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Gary V.H. Dahl, MD
Address 0 0
Lucile Packard Children's Hospital at Stanford University Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
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Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00002912