LeukemiaPhase 1NCT00002912
Combination Chemotherapy Plus PSC-833 in Treating Children With Refractory or Relapsed Acute Leukemia
A Phase 1 study testing etoposide, mitoxantrone hydrochloride and valspodar in people with Leukemia, run by National Cancer Institute (NCI) at 55 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Leukemia
- What is being tested?
- etoposide, mitoxantrone hydrochloride and valspodar
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 55 sitesin 3 countries
- Study dates
- Jan 1997to Mar 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
55 sites in 3 countries.
55 sites in 3 countries
United States50 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0752
Emory University Hospital - Atlanta
Atlanta, Georgia, 30322
Johns Hopkins Oncology Center
Baltimore, Maryland, 21231
Boston Floating Hospital Infants and Children
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Medical University of South Carolina
Charleston, South Carolina, 29425-0721
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, 60611
Children's Memorial Hospital, Chicago
Chicago, Illinois, 60614
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, 45229-3039
Children's Hospital of Columbus
Columbus, Ohio, 43205-2696
Simmons Cancer Center - Dallas
Dallas, Texas, 75235-9154
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, 76104
University of Florida Health Science Center
Gainesville, Florida, 32610-0296
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Texas Children's Cancer Center
Houston, Texas, 77030-2399
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030-4009
Indiana University Cancer Center
Indianapolis, Indiana, 46202-5265
University of Mississippi Medical Center
Jackson, Mississippi, 39216-4505
University of Kansas Medical Center
Kansas City, Kansas, 66160-7357
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of California San Diego Cancer Center
La Jolla, California, 92093-0658
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, 90095-1781
City of Hope National Medical Center
Los Angeles, California, 91010
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, 53792
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt Cancer Center
Nashville, Tennessee, 37232-6838
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Columbia Presbyterian Hospital
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73190
Children's Hospital of Orange County
Orange, California, 92668
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Primary Children's Medical Center
Salt Lake City, Utah, 84113
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78284-7811
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, 94115-0128
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305-5408
State University of New York - Upstate Medical University
Syracuse, New York, 13210
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
Canada3 sites
Montreal Children's Hospital
Montreal, Quebec, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Australia2 sites
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6001
About this study
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
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.
Read the detailed description
OBJECTIVES:
- 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etoposideDrug
mitoxantrone hydrochlorideDrug
valspodarDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: etoposide; Drug: mitoxantrone hydrochloride; Drug: valspodar |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2004 (estimated)
- Study startJan 1997
- Primary completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Gary V.H. Dahl, MD, Study chair, Lucile Packard Children's Hospital at Stanford University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002912
- Sponsor's protocol ID
- NCI-2012-01835
- Other IDs
- POG-9423, CCG-P9423, CDR0000065285
- Status last verified
- Aug 2010
- First submitted
- 1 Nov 1999
- Last updated
- 1 Feb 2013
- Results posted
- No
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.
PubMed 20209646Lacayo 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00002912
- Acronym / sponsor ID
- NCI-2012-01835
- Conditions
- Leukemia
- Keywords
- recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 1997
- Primary completion
- Mar 2006 (actual)
- First posted
- 29 Apr 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: etoposide, Drug: mitoxantrone hydrochloride, Drug: valspodarPatients 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. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etoposide | Drug | Arm I |
| mitoxantrone hydrochloride | Drug | Arm I |
| valspodar | Drug | Arm I |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2013.
- Results publication: PubMed 20209646O'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.
- Results publicationLacayo 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary V.H. Dahl, MD study chair
Lucile Packard Children's Hospital at Stanford University Medical Center
55 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing etoposide, mitoxantrone hydrochloride and valspodar in people with Leukemia, run by National Cancer Institute (NCI) at 55 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00002912, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2013.